Improving plant adaptation to soil antimony contamination: the synergistic contribution of arbuscular mycorrhizal fungus and olive mill waste.

BACKGROUND: This study aimed to investigate the alterations in biochemical and physiological responses of oat plants exposed to antimony (Sb) contamination in soil. Specifically, we evaluated the effectiveness of an arbuscular mycorrhizal fungus (AMF) and olive mill waste (OMW) in mitigating the effects of Sb contamination. The soil was treated with a commercial strain of AMF (Rhizophagus irregularis) and OMW (4% w/w) under two different levels of Sb (0 and 1500 mg kg-1 soil). RESULTS: The combined treatment (OMW + AMF) enhanced the photosynthetic rate (+ 40%) and chlorophyll a (+ 91%) and chlorophyll b (+ 50%) content under Sb condition, which in turn induced more biomass production (+ 67-78%) compared to the contaminated control plants. More photosynthesis in OMW + AMF-treated plants gives a route for phenylalanine amino acid synthesis (+ 69%), which is used as a precursor for the biosynthesis of secondary metabolites, including flavonoids (+ 110%), polyphenols (+ 26%), and anthocyanins (+ 63%) compared to control plants. More activation of phenylalanine ammonia-lyase (+ 38%) and chalcone synthase (+ 26%) enzymes in OMW + AMF-treated plants under Sb stress indicated the activation of phenylpropanoid pathways in antioxidant metabolites biosynthesis. There was also improved shifting of antioxidant enzyme activities in the ASC/GSH and catalytic pathways in plants in response to OMW + AMF and Sb contamination, remarkably reducing oxidative damage markers. CONCLUSIONS: While individual applications of OMW and AMF also demonstrated some degree of plant tolerance induction, the combined presence of AMF with OMW supplementation significantly enhanced plant biomass production and adaptability to oxidative stress induced by soil Sb contamination.

A literature review on pharmacological aspects, docking studies, and synthetic approaches of quinazoline and quinazolinone derivatives.

Quinazoline and quinazolinone derivatives piqued medicinal chemistry interest in developing novel drug candidates owing to their pharmacological potential. They are important chemicals for the synthesis of a variety of physiologically significant and pharmacologically useful molecules. Quinazoline and quinazolinone derivatives have anticancer, anti-inflammatory, antidiabetic, anticonvulsant, antiviral, and antimicrobial potential. The increased understanding of quinazoline and quinazolinone derivatives in biological activities provides opportunities for new medicinal products. The present review focuses on novel advances in the synthesis of these important scaffolds and other medicinal aspects involving drug design, structure-activity relationship, and action mechanisms of quinazoline and quinazolinone derivatives to help in the development of new quinazoline and quinazolinone derivatives.

In silico study and in vitro antileishmanial and antitrypanosomal evaluation of azopyrazoles and azopyrimidines.

Hydrazones 1-6, azo-pyrazoles 7-9 and azo-pyrimidines 10-15 are compounds that exhibit antibacterial activity. The mode of action and structures of these derivatives have been previously confirmed as antibacterial. In this investigation, biological screening and molecular docking studies were performed for derivatives 1-15, with compounds 2, 7, 8, 14 and 15 yielding the best energy scores (from -20.7986 to -10.5302 kcal/mol). Drug-likeness and in silico ADME prediction for the most potent derivatives, 2, 7, 8, 14 and 15, were predicted (from 84.46 to 96.85%). The latter compounds showed good recorded physicochemical properties and pharmacokinetics. Compound 8 demonstrated the strongest inhibition, which was similar to the positive control (eflornithine) against Trypanosoma brucei brucei (WT), with an EC50 of 25.12 and 22.52µM, respectively. Moreover, compound 14 exhibited the best activity against Leishmania mexicana promastigotes and Leishmania major promastigotes (EC50 =46.85; 40.78µM, respectively).

Production of Targeted Estrone Liposomes Using a Herringbone Micromixer.

Liposomes are spherical vesicles formed from bilayer lipid membranes that are extensively used in targeted drug delivery as nanocarriers to deliver therapeutic reagents to specific tissues and organs in the body. Recently, we have reported using estrone as an endogenous ligand on doxorubicin-encapsulating liposomes to target estrogen receptor (E.R.)-positive breast cancer cells. Estrone liposomes were synthesized using the thin-film hydration method, which is a long, arduous, and multistep process. Here, we report using a herringbone micromixer to synthesize estrone liposomes in a simple and rapid manner. A solvent stream containing the lipids was mixed with a stream of phosphate buffer saline (PBS) inside a microchannel integrated with herringbone-shaped ridges that enhanced the mixing of the two streams. The small scale involved enabled rapid solvent exchange and initiated the self-assembly of the lipids to form the required liposomes. The effect of different parameters on liposome size, such as the ratio between the flow rate of the solvent and the buffer solutions (FRR), total flow rate, lipid concentrations, and solvent type, were investigated. Using this commercially available chip, we obtained liposomes with a radius of 66.1 ± 11.2 nm (mean ± standard deviation) and a polydispersity of 22% in less than 15 minutes compared to a total of ~11 hours using conventional techniques. Calcein was encapsulated inside the prepared liposomes as a model drug and was released by applying ultrasound at different powers. The size of the prepared liposomes was stable over a period of one month. Overall, using microfluidics to synthesize Estrone-liposomes simplified the procedure considerably and improved the reproducibility of the resulting liposomes.

Definitive Closure Using an Ovine Reinforced Tissue Matrix in Contaminated Penetrating Abdominal Trauma.

BACKGROUND Cases involving penetrating abdominal trauma may be complex and often involve damage to multiple organ systems. Synthetic, biologic, and reinforced biologic matrices/reinforced tissue matrices (RBMs/RTMs) are frequently used in hernia repair and other surgical procedures requiring reinforcement, including trauma cases that require abdominal repair. CASE REPORT The first case was a 35-year-old male patient with a stab wound (SW) to the right side of the chest and the abdomen resulting in damage to the diaphragm, epicardium, liver, and duodenum. The second case was a 22-year-old male patient who suffered multiple traumas after an automated trencher accident, including a skull fracture with exposed brain and major lacerations to the shoulder and abdomen causing a large right-flank hernia. In both cases, OviTex® (TELA Bio, Inc., Malvern, PA), a reinforced tissue matrix (RTM), was used to help obtain and maintain abdominal wall closure. We also present an institutional economic analysis using data from the author's institution with average case cost and future projections for procedure volume and product usage volume through 2021. CONCLUSIONS We report favorable outcomes in a series of patients with contaminated (CDC Wound Class III) surgical fields who underwent abdominal wall closure and reinforcement with OviTex RTM. Our work adds to the growing body of literature suggesting that reinforced biologics offer a potential alternative to biological meshes in the setting of a contaminated surgical field. Additionally, in comparison to other commonly available biologic matrices, use of OviTex RTM may be a cost-effective option to achieve abdominal wall closure even in complex cases.

The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy.

BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.

Machine learning driven web-based app platform for the discovery of monoamine oxidase B inhibitors.

Monoamine oxidases (MAOs), specifically MAO-A and MAO-B, play important roles in the breakdown of monoamine neurotransmitters. Therefore, MAO inhibitors are crucial for treating various neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). In this study, we developed a novel cheminformatics pipeline by generating three diverse molecular feature-based machine learning-assisted quantitative structural activity relationship (ML-QSAR) models concerning MAO-B inhibition. PubChem fingerprints, substructure fingerprints, and one-dimensional (1D) and two-dimensional (2D) molecular descriptors were implemented to unravel the structural insights responsible for decoding the origin of MAO-B inhibition in 249 non-reductant molecules. Based on a random forest ML algorithm, the final PubChem fingerprint, substructure fingerprint, and 1D and 2D molecular descriptor prediction models demonstrated significant robustness, with correlation coefficients of 0.9863, 0.9796, and 0.9852, respectively. The significant features of each predictive model responsible for MAO-B inhibition were extracted using a comprehensive variance importance plot (VIP) and correlation matrix analysis. The final predictive models were further developed as a web application, MAO-B-pred ( https://mao-b-pred.streamlit.app/ ), to allow users to predict the bioactivity of molecules against MAO-B. Molecular docking and dynamics studies were conducted to gain insight into the atomic-level molecular interactions between the ligand-receptor complexes. These findings were compared with the structural features obtained from the ML-QSAR models, which supported the mechanistic understanding of the binding phenomena. The presented models have the potential to serve as tools for identifying crucial molecular characteristics for the rational design of MAO-B target inhibitors, which may be used to develop effective drugs for neurodegenerative disorders.

Correction: Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurodegenerative disease treatment.

[This corrects the article DOI: 10.1039/D3RA07035B.].

A comprehensive review of discovery and development of drugs discovered from 2020-2022.

To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.

The influence of supportive work environment on work-related stress and conflict management style among emergency care nurses: A descriptive correlational study.

BACKGROUND: Stress and conflict in emergency departments are inevitable but can be managed. A supportive work environment is key to helping emergency care providers, especially nurses, constructively manage work-related stress and conflict. AIM: The aim of this study was to assess the influence of supportive work environments on work-related stress and conflict management style among emergency care nurses. METHODS: A descriptive correlational research design was utilized. Data were collected from 221 staff nurses recruited from two university hospital emergency departments in Alexandria, Egypt. Three instruments were used: (1) perceived organizational support scale, (2) nurses' occupational stressors scale, and (3) conflict management style inventory. RESULTS: There was a highly significant correlation between supportive work environments and work-related stress (p = .000) and a significant correlation between supportive work environments and conflict management style (p = .026). Supportive work environments had a significant inverse negative relationship with work-related stress experienced by nurses (p = .001) and accounted for 51% of variance in work-related stress. Meanwhile, supportive work environments had a significant positive relationship with conflict management styles of nurses (p = .026). Work-related stress had a significant relationship with nurses' conflict management style (p = .000) and accounted for 45% of the variance in conflict management style. LINKING EVIDENCE TO ACTION: The style of conflict management modeled by staff within emergency departments can positively or negatively influence the work environment and level of work-related stress. There is a necessity to cultivate a supportive culture for nurses in emergency departments to develop skills for constructive conflict management styles to reduce work-related stress.

Discerning of isatin-based monoamine oxidase (MAO) inhibitors for neurodegenerative disorders by exploiting 2D, 3D-QSAR modelling and molecular dynamics simulation.

Almost a billion people worldwide suffer from neurological disorders, which pose public health challenges. An important enzyme that is well-known for many neurodegenerative illnesses is monoamine oxidase (MAO). Although several promising drugs for the treatment of MAO inhibition have recently been examined, it is still necessary to identify the precise structural requirements for robust efficacy. Atom-based, field-based, and GA-MLR (genetic algorithm multiple linear regression) models were created for this investigation. All of the models have strong statistical (R2 and Q2) foundations because of both internal and external validation. Our dataset's molecule has a higher docking score than safinamide, a well-known and co-crystallized MAO-B inhibitor, as we also noticed. Using the SwissSimilarity platform, we further inquired which of our docked molecules would be the best for screening. We chose ZINC000016952895 as the screen molecule with the best binding docking score (XP score = -13.3613). Finally, the 100 ns for the ZINC000016952895-MAO-B complex in our MD investigations is stable. For compounds that we hit, also anticipate ADME properties. Our research revealed that the successful compound ZINC000016952895 might pave the way for the future development of MAO inhibitors for the treatment of neurological disease.Communicated by Ramaswamy H. Sarma.

Long-term care facilities' response to the COVID-19 pandemic: An international, cross-sectional survey.

AIMS: To (i) assess the adherence of long-term care (LTC) facilities to the COVID-19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions. DESIGN: Cross-sectional survey. METHODS: Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVID-19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines. RESULTS: The adherence was significantly higher among facilities with more pre-pandemic in-service education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less work-life imbalance. CONCLUSIONS: Pre-pandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks. IMPACT: This is the first study to comprehensively examine the adherence of LTC facilities to COVID-19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to pre-pandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

"Click Chemistry": An Emerging Tool for Developing a New Class of Structural Motifs against Various Neurodegenerative Disorders.

Click chemistry is a set of easy, atom-economical reactions that are often utilized to combine two desired chemical entities. Click chemistry accelerates lead identification and optimization, reduces the complexity of chemical synthesis, and delivers extremely high yields without undesirable byproducts. The most well-known click chemistry reaction is the 1,3-dipolar cycloaddition of azides and alkynes to form 1,2,3-triazoles. The resulting 1,2,3-triazoles can serve as both bioisosteres and linkers, leading to an increase in their use in the field of drug discovery. The current Review focuses on the use of click chemistry to identify new molecules for treating neurodegenerative diseases and in other areas such as peptide targeting and the quantification of biomolecules.

In silico development of potential InhA inhibitors through 3D-QSAR analysis, virtual screening and molecular dynamics.

Tuberculosis is one of the most ancient infectious diseases known to mankind predating upper Paleolithic era. In the current scenario, treatment of drug resistance tuberculosis is the major challenge as the treatment options are limited, less efficient and more toxic. In our study we have developed an atom based 3D QSAR model, statistically validated sound with R2 > 0.90 and Q2 > 0.72 using reported direct inhibitors of InhA (2018-2022), validated by enzyme inhibition assay. The model was used to screen a library of 3958 molecules taken from Binding DB and candidates molecules with promising predicted activity value (pIC50) > 5) were selected for further analyzed screening by using molecular docking, ADME profiling and molecular dynamic simulations. The lead molecule, ZINC11536150 exhibited good docking score (glideXP = -11.634 kcal/mol) compared to standard triclosan (glideXP = -7.129 kcal/mol kcal/mol) and through molecular dynamics study it was observed that the 2nv6-complex of ZINC11536150 with Mycobacterium tuberculosis InhA (PDB entry: 2NV6) complex remained stable throughout the entire simulation time of 100 ns.Communicated by Ramaswamy H. Sarma.

Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment.

Eighteen isatin-based benzyloxybenzaldehyde derivatives from three subseries, ISB, ISFB, and ISBB, were synthesized and their ability to inhibit monoamine oxidase (MAO) was evaluated. The inhibitory activity of all synthesized compounds was found to be more profound against MAO-B than MAO-A. Compound ISB1 most potently inhibited MAO-B with an IC50 of 0.124 ± 0.007 µM, ensued by ISFB1 (IC50 = 0.135 ± 0.002 µM). Compound ISFB1 most potently inhibited MAO-A with an IC50 of 0.678 ± 0.006 µM, ensued by ISBB3 (IC50 = 0.731 ± 0.028 µM), and had the highest selectivity index (SI) value (55.03). The three sub-parental compounds, ISB1, ISFB1, and ISBB1, had higher MAO-B inhibition than the other derivatives, indicating that the substitutions of the 5-H in the A-ring of isatin diminished the inhibition of MAO-A and MAO-B. Among these, ISB1 (para-benzyloxy group in the B-ring) displayed more significant MAO-B inhibition when compared to ISBB1 (meta-benzyloxy group in the B-ring). ISB1 and ISFB1 were identified to be competitive and reversible MAO-B inhibitors, having Ki values of 0.055 ± 0.010, and 0.069 ± 0.025 µM, respectively. Furthermore, in the parallel artificial membrane penetration assay, ISB1 and ISFB1 traversed the blood-brain barrier in the in vitro condition. Additionally, the current study found that ISB1 decreased rotenone-induced cell death in SH-SY5Y neuroblastoma cells. In docking and simulation studies, the hydrogen bonding formed by the imino nitrogen in ISB1 and the pi-pi stacking interaction of the phenyl ring in isatin significantly aided in the protein-ligand complex's stability, effectively inhibiting MAO-B. According to these observations, the MAO-B inhibitors ISB1 and ISFB1 were potent, selective, and reversible, making them conceivable therapies for neurological diseases.

Development of a New Class of Monoamine Oxidase-B Inhibitors by Fine-Tuning the Halogens on the Acylhydrazones.

A total of 14 acyl hydrazine derivatives (ACH1-ACH14) were developed and examined for their ability to block monoamine oxidase (MAO). Thirteen analogues showed stronger inhibition potency against MAO-B than MAO-A. With a half-maximum inhibitory concentration of 0.14 µM, ACH10 demonstrated the strongest inhibitory activity against MAO-B, followed by ACH14, ACH13, ACH8, and ACH3 (IC50 = 0.15, 0.18, 0.20, and 0.22 µM, respectively). Structure-activity relationships suggested that the inhibition effect on MAO-B resulted from the combination of halogen substituents of the A- and/or B-rings. This series concluded that when -F was substituted to the B-ring, MAO-B inhibitory activities were high, except for ACH6. In the inhibition kinetics study, the compounds ACH10 and ACH14 were identified as competitive inhibitors, with Ki values of 0.097 ± 0.0021 and 0.10 ± 0.038 µM, respectively. In a reversibility experiment using the dialysis methods, ACH10 and ACH14 showed effective recoveries of MAO-B inhibition as much as lazabemide, a reversible reference. These experiments proposed that ACH10 and ACH14 were efficient, reversible competitive MAO-B inhibitors. In addition, the lead molecules showed good blood-brain barrier permeation with the PAMPA method. The molecular docking and molecular dynamics simulation study confirmed that the hit compound ACH10 can form a stable protein-ligand complex by forming a hydrogen bond with the NH atom in the hydrazide group of the compound.

Design and construction of novel pyridine-pyrimidine hybrids as selective COX-2 suppressors: anti-inflammatory potential, ulcerogenic profile, molecular modeling and ADME/Tox studies.

NSAIDs represent a mainstay in pain and inflammation suppression, and their actions are mainly based on inhibiting COX-1 and COX-2 enzymes.Due to the adverse effects of these drugs, especially on the stomach and heart, scientists efforts have been directed to manufacture selective COX-2 without cardiovascular side effects and with minimal effects on the stomach. The cardiovascular side effects are thought to be related to the chemical composition rather than mechanism of action of these drugs.Novel pyridopyrimidines, 9a-j, were prepared and their chemical structures were confirmed by NMR, mass and IR Spectra, and elemental analysis. The effect of the 9a-j compounds on COX-1 and COX-2 was assessed and it was found that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) was the most potent COX-2 inhibitor (IC50 = 0.54 uM) compared to celecoxib (IC50 = 1.11 uM) with selectivity indices of 6.56 and 5.12, respectively.The in vivo inhibition of paw edema of novel compounds 9a-j was measured using carrageenan-induced paw edema method, and that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) showed the best inhibitory activity in comparison with the other compounds and celecoxib.The gastroprotective effect of the potent derivatives 9d, 9e, 9f, 9 g and 9h was investigated. 2-Hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) and 7-(chlorophenyl)-hydrazino-5-(4-methoxyphenyl)-3H-pyrido[2,3-d)pyrimidin-4-one (9e) showed ulcer indices comparable to celecoxib (1 and 0.5 vs 0.5, respectively). Docking studies were carried out and they confirmed the mechanistic action of the designed compoundsCommunicated by Ramaswamy H. Sarma.

Cytotoxic and Antioxidant Potential of Launaea mucronata Forssk Essential Oil Growing in Northern Saudi Arabia.

Essential oils are naturally occurring multicomponent combinations of isoprenoids with distinctive odors that are produced by aromatic plants from mevalonic acid. They are extensively applied in aromatherapy for the treatment of various ailments. To investigate the potential therapeutic value of the ingredients in Launaea mucronata essential oil (EO), gas chromatography-mass spectrometry (GC-MS) analysis was used for essential oil characterization. Then, 2,2-diphenyl-1-picrylhydrazyl (DPPH), ß-carotene/linoleic acid, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays were used to evaluate the antioxidants. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to estimate the cytotoxicity. Following a thorough analysis of the GC-MS chromatogram, 87 components representing 97.98% of the entire EO mixture were identified. N-eicosane (10.92%), 2E,6Z-farnesol (10.74%), and 2Z,6E-farnesyl acetone (46.35%) were determined to be the major components of the oil. When the produced EO was evaluated for its antioxidant properties, it showed a strong inhibitory effect (%) of 65.34 at a concentration of 80 µg/mL. The results (g/mL) showed a positive response against the tested cell lines for HCT-116, MCF-7, and HepG2 (8.45, 10.24, and 6.78 g/mL, respectively). A high-concentration mixture of deadly components consisting of farnesol, bisabolol, eicosane, and farnesyl acetone may be responsible for this significant cytotoxic action, which was especially noticeable in the HepG2 cell line. Molecular docking occurred between farnesol and farnesyl acetone with the target residues of topoisomerases I and II, CDK4/cyclD1, and Aurora B kinases; these showed binding free energies ranging from -4.5 to -7.4 kcal/mol, thus demonstrating their antiproliferative action. In addition, farnesol and farnesyl acetone fulfilled most of the ADME and drug-likeness properties, indicating their activity.

Hesperidin Attenuates Titanium Dioxide Nanoparticle-Induced Neurotoxicity in Rats by Regulating Nrf-2/TNF-α Signaling Pathway, the Suppression of Oxidative Stress, and Inflammation.

Background: Titanium dioxide nanoparticles (TiO2NPs) are widely utilized and consumed mainly as food additives. Oxidative stress is considered to be the basic effect of TiO2NPs through biological interactions. Hesperidin (HSP) is a bioflavonoid (flavanone glycoside) with lipid-lowering, inflammation, oxidative stress suppression, antihypertensive, cancer-fighting, and antiedema effects. Objective: This study was to investigate the possible protective influences of HSP of subchronic oral TiO2NP exposure on the brains of rats, including neurotransmitters, oxidative stress/antioxidant parameters, inflammatory markers, and histological changes in the brains of adult male albino rats. Methodology: The experiment was executed on 80 albino rats. The animals were randomly divided into 4 equal groups. The first group served as a control; the second group was treated with oral doses of HSP (100 mg/kg Bw daily); the third group received TiO2NPs (200 mg/kg Bw orally daily); and the fourth group was treated with TiO2NPs and an oral dose of HSP daily for 8 weeks. Blood samples were obtained for biochemical analysis. Neurotransmitters, oxidative stress biomarker levels, and inflammatory markers were measured in brain homogenates. Histological examination of the brain was performed through H&E staining. Results: Coadministration of hesperidin with TiO2NPs orally for 8 weeks decreased the levels of MDA, TNF-α, AChE, and dopamine in brain homogenates, which were increased in the TiO2NP group. It increased the other oxidative biomarkers (SOD, CAT, and GPx) and Nrf-2 expression levels. Brain histological sections of the TiO2NP-treated group show degeneration, necrosis, congestion, and inflammatory cell infiltration that decreased markedly in the coadministration of hesperidin with the TiO2NP group. Conclusion: Hesperidin cotreatment offers significant protection against TiO2NP-induced oxidative stress and biochemical and histological alteration in the brain.