Biosynthesized silver nanoparticles mediated by Ammi visnaga extract enhanced systemic resistance and triggered multiple defense-related genes, including SbWRKY transcription factors, against tobacco mosaic virus infection.

BACKGROUND: Tobacco mosaic virus (TMV) is a highly infectious plant virus that affects a wide variety of plants and reduces crop yields around the world. Here, we assessed the effectiveness of using Ammi visnaga aqueous seed extract to synthesize silver nanoparticles (Ag-NPs) and their potential to combat TMV. Different techniques were used to characterize Ag-NPs, such as scanning and transmission electron microscopy (SEM, TEM), energy-dispersive X-ray spectroscopy (EDS), fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). RESULTS: TEM demonstrated that the synthesized Ag-NPs had a spherical form with an average size of 23-30 nm and a zeta potential value of -15.9 mV, while FTIR revealed various functional groups involved in Ag-NP stability and capping. Interestingly, the Pre-treatment of tobacco plants (protective treatment) with Ag-NPs at 100-500 µg/mL significantly suppressed viral symptoms, while the Post-treatment (curative treatment) delayed their appearance. Furthermore, protective and curative treatments significantly increased chlorophyll a and b, total flavonoids, total soluble carbohydrates, and antioxidant enzymes activity (PPO, POX and CAT). Simultaneously, the application of Ag-NPs resulted in a decrease in levels of oxidative stress markers (H2O2 and MDA). The RT-qPCR results and volcano plot analysis showed that the Ag-NPs treatments trigger and regulate the transcription of ten defense-related genes (SbWRKY-1, SbWRKY-2, JERF-3, GST-1, POD, PR-1, PR-2, PR-12, PAL-1, and HQT-1). The heatmap revealed that GST-1, the primary gene involved in anthocyanidin production, was consistently the most expressed gene across all treatments throughout the study. Analysis of the gene co-expression network revealed that SbWRKY-19 was the most central gene among the studied genes, followed by PR-12 and PR-2. CONCLUSIONS: Overall, the reported antiviral properties (protective and/or curative) of biosynthesized Ag-NPs against TMV lead us to recommend using Ag-NPs as a simple, stable, and eco-friendly agent in developing pest management programs against plant viral infections.

Foliar Application of Rhizobium leguminosarum bv. viciae Strain 33504-Borg201 Promotes Faba Bean Growth and Enhances Systemic Resistance Against Bean Yellow Mosaic Virus Infection.

The bean yellow mosaic virus (BYMV) is one of the most serious economic diseases affecting faba bean crop production. Rhizobium spp., well known for its high nitrogen fixation capacity in legumes, has received little study as a possible biocontrol agent and antiviral. Under greenhouse conditions, foliar application of molecularly characterized Rhizobium leguminosarum bv. viciae strain 33504-Borg201 to the faba bean leaves 24 h before they were infected with BYMV made them much more resistant to the disease while also lowering its severity and accumulation. Furthermore, the treatment promoted plant growth and health, as evidenced by the increased total chlorophyll (32.75 mg/g f.wt.) and protein content (14.39 mg/g f.wt.), as well as the improved fresh and dry weights of the plants. The protective effects of 33504-Borg201 greatly lowered the levels of hydrogen peroxide (H2O2) (4.92 µmol/g f.wt.) and malondialdehyde (MDA) (173.72 µmol/g f.wt.). The antioxidant enzymes peroxidase (1.58 µM/g f.wt.) and polyphenol oxidase (0.57 µM/g f.wt.) inhibited the development of BYMV in plants treated with 33504-Borg201. Gene expression analysis showed that faba bean plants treated with 33504-Borg201 had higher amounts of pathogenesis-related protein-1 (PR-1) (3.28-fold) and hydroxycinnamoyl-CoA quinate hydroxycinnamoyltransferase (4.13-fold) than control plants. These findings demonstrate the potential of 33,504-Borg201 as a cost-effective and eco-friendly method to protect faba bean plants against BYMV. Implementing this approach could help develop a simple and sustainable strategy for protecting faba bean crops from the devastating effects of BYMV.

Chemical Characterization, Evaluation of Acute Oral Toxicity, and Anti-Diabetic Activity of Aloe sabaea Flowers Extract on Alloxan-Induced Diabetic Rats.

The study aimed to conduct chemical profiling, acute in-vivo toxicity evaluation, and the potential anti-diabetic effect of standardized Aloe sabaea flowers ethanolic extracts (ASFEE) on alloxan-induced diabetic rats. The chemical composition was analyzed using GC-MS and TLC techniques. The oral acute toxicity study was performed according to the WHO 2000 and the OECD 420 guidelines. Furthermore, anti-diabetic activity was investigated using two doses of ASFEE (0.2 and 0.5 g/kg/day BW, p.o.) compared with glibenclamide (5 mg/kg/day, p.o.). A molecular docking investigation of the identified components with the PTPN9 enzyme was performed to figure out the proposed anti-diabetic mechanism. GC-MS analysis displayed the existence of 18 compounds; most of the compounds were fatty acids and their esters, and phytosterols. Total phenolic and flavonoid contents were 42.00±1.26 mg GAE/g DW and 22.21±1.55 mg QE/g DW, respectively. The results of the in-vivo toxicity study revealed the absence of noticeable signs of toxicity or mortality at various doses establishing the safety of the tested extract. The estimated LD50 value was higher than 10 g/kg. Antidiabetic action exhibited a noticeable decline in fasting blood glucose (FBG) levels comparable to glibenclamide with no inducing intense hypoglycemia and considerable excess weight.

Pathological characterization and management of Lasiodiplodia theobromae, a hemi-biotroph with an interkingdom host range.

Heart rot disease, caused by Lasiodiplodia theobromae, is destructive for date palms and other woody plants. The disease was reported in several oasis in Egypt, and the pathogen was found in association with infected trees suffering die-back and rachis blight. Seven phylogenetically distinct fungal isolates were selected, and their pathogenicity was confirmed on date palms. The isolates exhibited variable degrees of virulence on inoculated leaves, which confirms the variation. We examined the antifungal effect of microbial bioagents and plant extracts on heart rot disease. The isolates of Trichoderma spp. gave moderate reduction of the pathogen's linear growth (40-60%), while their exudates were ultimately ineffective. Bacillus spp. isolates, except for B. megaterium, were more effective against spore germination as they gave 80-90% reduction on average. Among the examined plant extracts garlic sap gave 98.67% reduction of linear growth followed by artemisia (15.5%) and camphor (24.8%). The extraction methods greatly influenced the antifungal efficiency of each extract as exposure to organic solvents significantly decreased the efficiency of all extracts, while hot water extraction negatively affected garlic sap only. Successful bioagents and plant extracts were further assayed for the suppression of heart rot disease on date palms. Both T. album and T. harzianum gave comparable degrees of suppression as by commercial fungicides. In addition, treatment before or during pathogen inoculation was the most effective as it significantly enhanced the expression of defense-related enzymes. Our findings suggest bio-pesticides possessing a dual role in disease suppression and defense boosters for date palms suffering heart rot disease.

Novel 2-[thio]acetamide linked quinazoline/1,2,4-triazole/chalcone hybrids: Design, synthesis, and anticancer activity as EGFR inhibitors and apoptotic inducers.

Novel triazoloquinazolines carrying the 2-[thio]acetamide entity (4 and 5a-d) and triazoloquinazoline/chalcone hybrids incorporating the 2-[thio]acetamide linker (8a-b and 9a-f) were developed as anticancer candidates. NCI screening of the synthesized compounds at 10 µM concentration displayed growth inhibition not only up to 99.74% as observed for 9a but also a lethal effect could be achieved as stated for compounds 9c (RPMI-8226 and HCT-116) and 8b, 9a, and 9e on the HCT-116 cell line. The antiproliferative activity was determined for the chalcone series on three cell lines: RPMI-8226, HCT-116, and MCF-7. Compounds 8b, 9a, 9b, and 9f were the most active ones. To understand the mechanistic study, the inhibitory effect on the epidermal growth factor receptor (EGFR) kinase was evaluated. The results stated that the activity of compound 8b (IC50 = 0.07 µM) was near that of the reference drug erlotinib (IC50 = 0.052 µM) whereas compound 9b (IC50 = 0.045 µM) was found to be more potent than erlotinib. Both compounds 8b and 9b were selected for cell cycle analysis and apoptotic assays. Moreover, molecular docking results of the selected chalcone hybrids showed high binding scores and good binding affinities especially for 8b and 9b, which were consistent with the biological activity (EGFR).

Dual COX-2 and 15-LOX inhibition study of novel 4-arylidine-2-mercapto-1-phenyl-1H-imidazolidin-5(4H)-ones: Design, synthesis, docking, and anti-inflammatory activity.

Novel arylidene-5(4H)-imidazolone derivatives 4a-r were designed and evaluated as multidrug-directed ligands, that is, inflammatory, proinflammatory mediators, and reactive oxygen species (ROS) inhibitors. All of the tested compounds showed cyclooxygenase (COX)-1 inhibitory effect more than celecoxib and less than indomethacin and also demonstrated an improved inhibitory activity against 15-lipoxygenase (15-LOX). Compounds 4f, 4l, and 4p exhibited COX-2 selectivity comparable to that of celecoxib, while 4k was the most selective COX-2 inhibitor. Interestingly, the screened results showed that compound 4k exhibited a superior inhibition effect against 15-LOX and was found to be the most selective COX-2 inhibitor over celecoxib, whereas compound 4f showed promising COX-2 and 15-LOX inhibitory activities besides its inhibitory effect against ROS production and its lowering effect of both tumor necrosis factor-α and interleukin-6 levels by ∼80%. Moreover, compound 4f attenuated the lipopolysaccharide-mediated increase in NF-κB activation in RAW 264.7 macrophages. The preferred binding affinity of these molecules was confirmed by docking studies. We conclude that arylidene-5(4H)-imidazolone scaffolds provide promising hits for developing new synthons with anti-inflammatory and antioxidant activities.

Triple targeting of mutant EGFRL858R/T790M, COX-2, and 15-LOX: design and synthesis of novel quinazolinone tethered phenyl urea derivatives for anti-inflammatory and anticancer evaluation.

We designed and synthesised novel quinazolinone tethered phenyl urea derivatives (6a-p) that triple target the double mutant EGFRL858R/T790M, COX-2, and 15-LOX. Compounds (6e, 6d, 6j, 6m, and 6n) not only had low micromolar IC50 inhibitory activities against the three targets, but they also showed good selectivity for COX-2 over COX-1 and for EGFRL858R/T790M over wild-type EGFR. Except for 6e and 6n, all of the tested compounds inhibited the NO production significantly more potently than celecoxib, diclofenac, and indomethacin. Compounds 6i and 6k reduced ROS levels more effectively than celecoxib and diclofenac. In terms of inhibiting TNF-α production, 6o-treated cells showed TNF-α level, which is ∼10 times lower than celecoxib. Furthermore, 6e and 6j had the highest anticancer activity against the breast cancer cell line BT-459 with growth inhibition percentages of 67.14 and 70.07%, respectively. Docking studies confirm their favoured binding affinity. The proposed compounds could be promising multi-targeted leads.

Does Ultrasound Guidance Provide Pain Relief During Intrauterine Contraceptive Device Insertion? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate ultrasound guidance effect in pain relief during intrauterine device (IUD) insertion. METHODS: Four different databases were searched from inception till June 2022. We selected randomized controlled trials (RCTs) that compared transabdominal ultrasound guidance versus traditional non-guided IUD insertion among women undergoing IUD placement for contraception. We used Revman software during performing our meta-analysis. Our primary outcome was the pain score during IUD insertion as evaluated by the Visual Analog Scale (VAS). Our secondary outcomes were the procedure insertion time, satisfaction, and incidences of complications and misplaced IUDs. RESULTS: Seven RCTs were retrieved with a total number of 1267 patients. There was a significant reduction in the VAS pain score during IUD insertion among the ultrasound-guided group (MD = -1.91, 95% CI [-3.08, -0.73], P = .001). The procedure insertion time was significantly shorter within the ultrasound guidance group compared with the control group (MD = -1.35, 95% CI [-1.81, -0.88], P < .001). Moreover, more women were significantly satisfied with the procedure among the ultrasound-guided group (P < .001). In addition, ultrasound-guided IUD insertion was linked to significant decline in incidences of complications and misplaced IUDs. CONCLUSION: Ultrasound guidance can be used as a modified technique during IUD insertion as it decreases pain, procedure time, and rates of complications and misplaced IUDs with better patient satisfaction.

Ultrasound detected synovitis, tenosynovitis and erosions in hand and wrist joints: a comparative study between rheumatoid and psoriatic arthritis.

OBJECTIVES: Musculoskeletal ultrasound (MSUS) has been introduced as a valuable simple imaging tool for arthritis. The objective was to assess the role of ultrasound (US) in the differential diagnosis between rheumatoid arthritis (RA) and psoriatic arthritis (PsA) at the wrist and hand joints and tendons. MATERIAL AND METHODS: Thirty-five patients (20 RA and 15 PsA) with symptomatic involvement of at least one of the hand and/or wrist joints for > 6 weeks were included. Bilateral wrists (distal radioulnar, radiocarpal and midcarpal joints), hands (1st-5th metacarpophalangeal [MCP], 2nd-5th proximal interphalangeal [PIP] and 1st-5th distal interphalangeal [DIP] joints), flexor tendons and extensor compartments at the level of the wrist joint were examined sonographically. Synovial hypertrophy, joint effusion, erosions and tenosynovitis were diagnosed according to Outcome Measures in Rheumatology definitions. The findings were correlated with clinical, laboratory and disease activity indices. RESULTS: Among 680 and 510 joints examined in RA and PsA respectively, certain US features such as synovitis and erosions at the DIP were exclusively detected in PsA (p < 0.001). Synovitis was frequently detected at the distal radioulnar joints (DRUJ) in RA in comparison to PsA patients (52.5% vs. 26.7% respectively, p = 0.029). Joint effusion was more frequently detected at radiocarpal and midcarpal joints in RA compared to PsA (p = 0.047, 0.039 respectively), whereas erosions were significantly more frequently detected at radiocarpal joints in RA versus PsA patients (45% vs. 20% respectively, p = 0.029). Tenosynovitis was significantly more frequently detected at the extensor tendons in RA and at the flexor tendons in PsA patients (p = 0.021, 0.022 respectively). CONCLUSIONS: There are significant differences in the musculoskeletal US findings of the hand and wrist that joints help to distinguish between RA and PsA.

Antiviral, antifungal, and insecticidal activities of Eucalyptus bark extract: HPLC analysis of polyphenolic compounds.

In this study, the antiviral, antifungal, and insecticidal and HPLC analysis of polyphenolic compounds of Eucaluptus camaldulensis Dehnh. bark extract (ECBE) were evaluated. Three fungi, namely Fusarium culmorum MN398395, Rhizoctonia solani MN398397, and Botrytis cinerea MN398399 were used to colonize wood blocks of chinaberry that was previously treated with different concentrations of ECBE at 1%, 2%, and 3%. Antiviral evaluations (protective, curative, and inactivating activities) of the extract at 100 µg/mL were assayed against Tobacco mosaic virus (TMV) MG264131 using the half-leaf method to determine the inhibitory percentage towards the number of local lesions. The protective treatment of Nicotiana glutinosa leaves exhibited excellent activity (72.22%) with a 91.1-fold reduction in TMV-CP accumulation in infected tissues. Furthermore, Real-time quantitative PCR revealed that the expression level of PAL and PR-1 (salicylic acid marker) genes were significantly up regulated at four days-post inoculation (dpi) for all treatments compared to untreated leaves. The insecticidal effect was screened by the contact and fumigant methods against Tribolium castaneum (Herbst) and Sitophilus oryzae L. in vitro. In contact assay, all concentrations 1, 5, 10, 20 and 30 ppm caused 100% toxicity to the two tested pests within 24 h, whereas the fumigant assay, gave the highest mortality against T. castaneum and S. oryzae by 20 ppm (61.66%) and 30 ppm (57.77%), respectively after 24 h. The HPLC analysis of ECBE revealed that benzoic acid, quinol, salicylic acid, myricetin, and rutin were the most abundant polyphenolic compounds found in the extract. In conclusion, when the extract concentration increases, the growth of fungal mycelia was decreased compared with the control, especially against F. culmorum. According to the hypotheses of the results, the ECBE recommended to prevent the wood from discoloration, fungal molds by acting as bio-preservative, also trigger the resistance of plants against viral infection and high toxicity against stored-product insects.

X-Ray Crystal Structure of a 2-Amino-3,4-dihydroquinazoline 5-HT3 Serotonin Receptor Antagonist and Related Analogs.

Certain 2-amino-3,4-dihydroquinazolines bind at 5-HT3 serotonin receptors and act as antagonists (e.g. 6-chloro) whereas others bind with little to no affinity and lack functional activity (e.g. 8-chloro). The purpose of this investigation was to gain insight as to why this might be the case. X-Ray crystallographic studies revealed that the N-C-N distances in the examined analogs are nearly identical (1.31 - 1.34 Å), suggesting that differences in N-C-N delocalization does not account for differences in affinity/action. Homology modeling hydrophatic interactions (HINT) analysis revealed that the 6-chloro analog formed a greater number, and more favorable, interactions with the receptor, whereas the 8-chloro analog formed fewer, and unfavorable, interactions. The affinity and activity of the 6-chloro quinazoline relative to its 8-chloro counterpart are unrelated to the N-C-N delocalization pattern but might be related to specific (favorable and unfavorable) interactions of quinazoline substituents with certain receptor features as determined by HINT analysis.

Eco-friendly novel deconvoluted synchronous spectrofluorimetric approach for the determination of favipiravir, levodropropizine and moxifloxacin hydrochloride as an effective therapeutic combination for COVID-19; application in laboratory prepared mixtures and spiked human plasma.

In this work, a green, fast, and simple synchronous spectrofluorimetric approach has been developed to simultaneously determine favipiravir, levodropropizine, and moxifloxacin hydrochloride as co-administered medications for COVID-19 treatment in pure form and spiked human plasma. The synchronous fluorescence spectroscopy technique to analyze the studied drugs at Δλ = 110 nm enabled the determination of levodropropizine at 360 nm. Then, applying Fourier Self-Deconvolution to each spectra to measure favipiravir and moxifloxacin hydrochloride at peak amplitudes of 431 nm and 479 nm, respectively, without any interference. Favipiravir, levodropropizine, and moxifloxacin hydrochloride could be sensitively determined using the described approach over concentration ranges of 20-300 ng/mL, 10-600 ng/mL, and 50-500 ng/mL, respectively. The method's validation was carried out effectively in accordance with guidelines recommended by the ICH. Finally, the Eco-scale and Green Analytical Procedure Index (GAPI) techniques have been used to evaluate the greenness of the proposed method.

Green chemometric-assisted UV-spectrophotometric methods for the determination of favipiravir, cefixime and moxifloxacin hydrochloride as an effective therapeutic combination for COVID-19; application in pharmaceutical form and spiked human plasma.

As pharmaceutical analysis progresses towards environmental sustainability, there is a growing need to enhance the safety and health conditions for analysts. Consequently, the incorporation of chemometrics into environmentally friendly analytical methods represents a promising approach. Favipiravir, cefixime, and moxifloxacin hydrochloride have been currently used in COVID-19 treatment. In this study, we develop spectrophotometric methods depending on chemometric based models to measure the levels of favipiravir, cefixime, and moxifloxacin hydrochloride in pharmaceutical preparations and spiked human plasma. It is challenging to determine favipiravir, cefixime, and moxifloxacin simultaneously because of overlap in their UV absorption spectra. Two advanced chemometric models, partial least square (PLS) and genetic algorithm (GA), have been developed to provide better predictive abilities in spectrophotometric determination of the drugs under study. The described models were created using a five-level, three-factor experimental design. The outcomes of the models have been thoroughly assessed and interpreted, and a statistical comparison with recognized values has been taken into consideration. The analytical eco-scale and the green analytical procedure index (GAPI) evaluation methods were also utilized to determine how environmentally friendly the mentioned models were. The outcomes demonstrated how well the models described complied with the environmental requirements.

Transcriptional responses and secondary metabolites variation of tomato plant in response to tobacco mosaic virus infestation.

The present study focused on the impact of infection with the tobacco mosaic virus (TMV). Specifically, changes in phytochemicals and gene activity related to pathogenesis-related and phenylpropanoid pathway genes in tomato plants (Solanum lycopersicum L.) during a period of 2-14 days post-inoculation (dpi). According to TEM investigation and coat protein sequence analysis, the purified TMV Egyptian AM isolate (PP133743) has a rod-shaped structure with a diameter of around 110 nm. The RT-qPCR analysis revealed that PR-1 showed an initial increase after TMV infection, as seen in the time-course analysis. In contrast, PR-2 was consistently elevated throughout the infection, suggesting a stronger reaction to the virus and suppressing PAL expression at 6 to 14 dpi. The expression levels of HQT and CHS transcripts exhibited alternating patterns of up-regulation and down-regulation at different time intervals. The HPLC and GC-MS analysis of control- and TMV-infected tomato extracts revealed that different phenolic, flavonoid, and fatty acid compounds were increased (such as naringenin, rutin, flavone, ferulic acid, and pyrogallol) or significantly decreased (such as salicylic acid and chlorogenic acid) after TMV infection. The ability of TMV to inhibit most polyphenolic compounds could potentially accelerate the viral life cycle. Consequently, focusing on enhancing the levels of such suppressed compounds may be critical for developing plant viral infection management strategies.

Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract.

The research into the use of plants as plentiful reservoirs of bioactive chemicals shows significant potential for agricultural uses. This study focused on analyzing the chemical composition and potency of an ethanolic extract obtained from the aerial parts (leaves and stems) of Salsola kali against potato pathogenic fungal and bacterial pathogens. The isolated fungal isolates were unequivocally identified as Fusarium oxysporum and Rhizoctonia solani based on morphological characteristics and internal transcribed spacer genetic sequencing data. The antifungal activity of the extract revealed good inhibition efficacy against R. solani (60.4%) and weak activity against F. oxysporum (11.1%) at a concentration of 5,000 µg/mL. The S. kali extract exhibited strong antibacterial activity, as evidenced by the significant inhibition zone diameter (mm) observed in all three strains of bacteria that were tested: Pectobacterium carotovorum (13.33), Pectobacterium atrosepticum (9.00), and Ralstonia solanacearum (9.33), at a concentration of 10,000 µg/mL. High-performance liquid chromatography analysis revealed the presence of several polyphenolic compounds (µg/g), with gallic acid (2942.8), caffeic acid (2110.2), cinnamic acid (1943.1), and chlorogenic acid (858.4) being the predominant ones. Quercetin and hesperetin were the predominant flavonoid components, with concentrations of 1110.3 and 1059.3 µg/g, respectively. Gas chromatography-mass spectrometry analysis revealed the presence of many bioactive compounds, such as saturated and unsaturated fatty acids, diterpenes, and phytosterols. The most abundant compound detected was n-hexadecanoic acid, which accounted for 28.1%. The results emphasize the potential of S. kali extract as a valuable source of bioactive substances that possess good antifungal and antibacterial effects, which highlights its potential for many agricultural uses.

Trichoderma afroharzianum TRI07 metabolites inhibit Alternaria alternata growth and induce tomato defense-related enzymes.

Identifying a viable substitute for the limited array of current antifungal agents stands as a crucial objective in modern agriculture. Consequently, extensive worldwide research has been undertaken to unveil eco-friendly and effective agents capable of controlling pathogens resistant to the presently employed fungicides. This study explores the efficacy of Trichoderma isolates in combating tomato leaf spot disease, primarily caused by Alternaria alternata. The identified pathogen, A. alternata Alt3, was isolated and confirmed through the ITS region (OQ888806). Six Trichoderma isolates were assessed for their ability to inhibit Alt3 hyphal growth using dual culture, ethyl acetate extract, and volatile organic compounds (VOCs) techniques. The most promising biocontrol isolate was identified as T. afroharzianum isolate TRI07 based on three markers: ITS region (OQ820171), translation elongation factor alpha 1 gene (OR125580), and RNA polymerase II subunit gene (OR125581). The ethyl acetate extract of TRI07 isolate was subjected to GC-MS analysis, revealing spathulenol, triacetin, and aspartame as the main compounds, with percentages of 28.90, 14.03, and 12.97%, respectively. Analysis of TRI07-VOCs by solid-phase microextraction technique indicated that the most abundant compounds included ethanol, hydroperoxide, 1-methylhexyl, and 1-octen-3-one. When TRI07 interacted with Alt3, 34 compounds were identified, with major components including 1-octen-3-one, ethanol, and hexanedioic acid, bis(2-ethylhexyl) ester. In greenhouse experiment, the treatment of TRI07 48 h before inoculation with A. alternata (A3 treatment) resulted in a reduction in disease severity (16.66%) and incidence (44.44%). Furthermore, A3 treatment led to improved tomato growth performance parameters and increased chlorophyll content. After 21 days post-inoculation, A3 treatment was associated with increased production of antioxidant enzymes (CAT, POD, SOD, and PPO), while infected tomato plants exhibited elevated levels of oxidative stress markers MDA and H2O2. HPLC analysis of tomato leaf extracts from A3 treatment revealed higher levels of phenolic acids such as gallic, chlorogenic, caffeic, syringic, and coumaric acids, as well as flavonoid compounds including catechin, rutin, and vanillin. The novelty lies in bridging the gap between strain-specific attributes and practical application, enhancing the understanding of TRI07's potential for integrated pest management. This study concludes that TRI07 isolate presents potential natural compounds with biological activity, effectively controlling tomato leaf spot disease and promoting tomato plant growth. The findings have practical implications for agriculture, suggesting a sustainable biocontrol strategy that can enhance crop resilience and contribute to integrated pest management practices.

Evaluation of in-vitro antioxidant activity, acute oral toxicity, and pancreatic and hepatic protective effects of Aloe rubroviolacea flowers extract against CCl4 toxicity in a rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe rubroviolacea (Arabian Aloe) was widely cultured and commonly used in traditional medicine. Aloe species was highly recommended in folk medicine for abdominal pain, intestinal infection, intestinal colic, obesity, and gynaecological pain after childbirth. AIM OF THE WORK: The present work aimed to conduct chemical profiling, in-vitro antioxidant activity, in-vivo oral acute toxicity study of A. rubroviolacea flowers ethanolic extract (ARFEE) along with exploring pancreatic and hepatic protective effects of ARFEE against carbon tetrachloride (CCl4) toxicity in a rat model. Molecular docking study of ARFEE and 3D structure activity relationship was also demonstrated to investigate the proposed antioxidant mechanism. MATERIALS AND METHODS: The chemical composition was analyzed using gas chromatography-mass spectrometry (GC-MS) and thin layer chromatography (TLC) techniques. Total phenolic and flavonoid contents in ARFEE were estimated by Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. In-vitro antioxidant DPPH assay was performed using ascorbic acid as a reference standard. Moreover, In-vivo acute toxicity study using fixed doses of ARFEE (0.1, 0.5, 1, 2 and 3 g/kg orally) was conducted. CCl4 toxicity was induced by using a single dose of CCl4 (1 ml/kg, i.p.) on 5th day, silymarin (50 mg/kg/day, orally) as a standard and two different doses of ARFEE (250, 500 mg/kg, orally) daily for 5 days before CCl4 injection. RESULTS: GC-MS analysis displayed the existence of 36 chemical compounds, the majority of which were fatty acids and their esters, in addition to phytosterols. The total phenolic content of ARFEE was 25.09 ± 1.65 mg of gallic acid equivalent/g extract dry weight (mg GAE/g DW), while the total flavonoid content was 17.48 ± 0.64 mg of quercetin equivalent/g extract dry weight (mg QE/g DW). Our results showed that the ARFEE had a potential in-vitro antioxidant activity as strong as ascorbic acid. No mortality or signs of toxicity were observed after ARFEE intake. Additionally, ARFEE ameliorated CCl4 toxicity on hepatic and pancreatic tissues. Molecular docking study resulted in potent promising natural compounds contained in ARFEE with anti-oxidant potential. CONCLUSION: Based on oral safety, good anti-oxidant and pancreato- and hepato-protective activities of ARFEE against CCl4 toxicity, ARFEE is probably a potent agent for treatment of liver ailments.

Triazolopyrimidine derivatives: An updated review on recent advances in synthesis, biological activities and drug delivery aspects.

Molecules containing triazolopyrimidine core showed diverse biological activities, including anti-Alzheimer, antidiabetes, anticancer, antimicrobial, antituberculosis, antiviral, antimalarial, anti-inflammatory, anti-parkinsonism activities, and treatment of glaucoma. Triazolopyrimidines have around 8 isomeric structures including the most stable 1,2,4-triazolo[1,5-a] pyrimidine ones. Triazolopyrimidines were obtained by using various chemical reactions, among them a) 1,2,4-triazole nucleus annulation to pyrimidine, b) pyrimidines annulation to 1,2,4-triazole structure, c) 1,2,4-triazolo[l,5-a] pyrimidines rearrangement, and d) pyrimido-tetrazine rearrangement. This review discusses synthetic methods, recent pharmacological actions and drug delivery perspectives of triazolopyrimidines.

Productivity and Phytochemicals of Asclepias curassavica in Response to Compost and Silver Nanoparticles Application: HPLC Analysis and Antibacterial Activity of Extracts.

The application of compost and metallic nanoparticles has a significant impact on the productivity and chemical composition of horticulture plants. In two subsequent growing seasons, 2020 and 2021, the productivity of Asclepias curassavica L. plants treated with various concentrations of silver nanoparticles (AgNPs) and compost was assessed. In the pot experiments, the soil was amended with 25% or 50% compost, and the plants were sprayed with 10, 20, and 30 mg/L of AgNPs. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction analysis (XRD), and dynamic light scattering (DLS) were used to characterize AgNPs. The TEM measurements of AgNPs showed that the particles had spherical forms and ranged in size from roughly 5 to 16 nm. Leaf methanol extracts (LMEs) were prepared from the treated plants and assayed against the growth of two soft rot bacteria, Dickeya solani and Pectobacterium atrosepticum. The maximum plant height, diameter, number of branches/plant, total fresh weight (g), total dry weight (g), and leaf area (cm2) was recorded when levels of 25% compost + AgNPs 20 mg/L, 25% compost, or 50% + AgNPs 20 mg/L, 25% compost + AgNPs 30 mg/L or 50% compost + AgNPs 20 mg/L, 50% compost + AgNPs 20 mg/L, 50% compost + AgNPs 30 or 20 mg/L, and 25% compost + AgNPs 30 mg/L, respectively, were applied. The plants treated with 25% or 50% compost + 30 mg/L AgNPs showed a high chlorophyll content, while the plants treated with 50% compost + AgNPs 30 mg/L or 20 mg/L showed the highest extract percentages. The highest inhibition zones (IZs), 2.43 and 2.2 cm, against the growth of D. solani were observed in the LMEs (4000 mg/L) extracted from the plants treated with compost (v/v) + AgNPs (mg/L) at the levels of 50% + 30 and 25% + 30, respectively. The highest IZs, 2.76 and 2.73 cm, against the growth of P. atrosepticum were observed in the LMEs (4000 mg/L) extracted from the plants treated at the levels of 50% + 30 and 25% + 30, respectively. Several phenolic compounds such as syringic acid, p-coumaric acid, chlorogenic acid, cinnamic acid, ellagic acid, caffeic acid, benzoic acid, gallic acid, ferulic acid, salicylic acid, pyrogallol, and catechol, as well as flavonoid compounds such as 7-hydroxyflavone, naringin, rutin, apigenin, quercetin, kaempferol, luteolin, hesperidin, catechin, and chrysoeriol, were identified in the LMEs as analyzed by HPLC with different concentrations according to the treatment of compost + AgNPs used for the plants. In conclusion, the specific criteria that were utilized to measure the growth of A. curassavica revealed the novelty of compost and AgNPs combination treatments, particularly at a concentration of 50% compost + AgNPs 30 mg/L or 20 mg/L, which is better for the growth and phytochemical production of A. curassavica in the field.

Magic shotgun approach to anti-inflammatory pharmacotherapy: Synthesis of novel thienopyrimidine monomers/heterodimer as dual COX-2 and 15-LOX inhibitors endowed with potent antioxidant activity.

Emerging evidence points to the intertwining framework of inflammation and oxidative stress in various ailments. We speculate on the potential impact of the magic shotgun approach in these ailments as an attempt to mitigate the drawbacks of current NSAIDs. Hence, we rationally designed and synthesized new tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine monomers/heterodimer as dual selective COX-2/15-LOX inhibitors with potent antioxidant activity. The synthesized compounds were challenged with diverse in vitro biological assays. Regarding the monomeric series, compound 5k exerted the highest COX-2 inhibitory activity (IC50 = 0.068 µM, SI = 160.441), while compound 5i showed the highest 15-LOX inhibitory activity (IC50 = 1.97 µM). Surpassing the most active monomeric members, the heterodimer 11 stemmed as the most potent and selective one in the whole study (COX-2 IC50 = 0.065 µM, SI = 173.846, 15-LOX IC50 = 1.86 µM). Heterodimer design was inspired by the cross-talk between the partner monomers of the COX-2 isoform. Moreover, some of our synthesized compounds could significantly reverse the LPS-enhanced production of ROS and proinflammatory cytokines (IL-6, TNF-α, and NO) in RAW 264.7 macrophages. Again, the heterodimer showed the strongest suppressor activity against ROS (IC50 = 18.79 µM) and IL-6 (IC50 = 4.15 µM) production outperforming the two references, celecoxib and diclofenac. Regarding NO suppressor activity, compound 5j (IC50 = 18.62 µM) surpassed the two references. Only compound 5a significantly suppressed TNF-α production (IC50 = 19.68 µM). Finally, molecular modeling simulated the possible binding scenarios of our synthesized thienopyrimidines within the active sites of COX-2 and 15-LOX. These findings suggest that those novel thienopyrimidines are promising leads showing pharmacodynamics synergy against the selected targets.