Median Inhibitory Concentration Research Articles

Bioavailability and phytotoxicity of clomazone to corn depend on soil characteristics and can be estimated by in situ pore water

AbstractBACKGROUNDThe injury caused by residual herbicides in soils to subsequent crops has been frequently reported and is largely related to soil physicochemical properties. Elucidating the interactions between herbicide toxicity and soil properties could help assess its phytotoxicity based on local soil characteristics. Here, the influence of soil properties on the accumulation and toxicity of clomazone as a model compound to corn was explored to obtain a universal indicator for estimating the toxicity of herbicides against crops.RESULTSThe phytotoxicity of clomazone to corn differed in the five tested soils with the median inhibitory concentration (IC50) values, according to the added concentration, fluctuating between 2.80 and 26.97 mg/kg. The uptake of clomazone by corn was primarily affected by its sorption onto soils and showed a positive correlation with the concentration of clomazone in in situ pore water (CIPW) (R2 ≥ 0.775, P < 0.001). In contrast to results derived from traditional soil clomazone concentrations (Csoil) determined through organic solvent extraction, consistent IC50 values (1.344–1.626 mg/L) were obtained based on CIPW in all five soils with a much lower coefficient of variation.CONCLUSIONSThese findings indicate that measuring the concentration of clomazone in in situ pore water provides a reliable and comparable method for evaluating its bioavailability and phytotoxicity on corn. Using CIPW rather than Csoil as a herbicide indicator is more accurate for assessing its actual phytotoxicity. These results are important for the scientific application of clomazone and the safe production of corn. © 2024 Society of Chemical Industry.

Antioxidant Properties of Freeze Dried Mix Fruits and Vegetables Product ‘Miss Freezy’ Using Lyophilization Method

Background: The proper processing of fruits and vegetable-based food products will improve appearance, taste, bioactivities, and preservation. Freeze-dried (FD) or lyophilization of foods extends shelf life and preserves food's nutritional value and bioactivities. The objective of this study is to compare the antioxidant properties, nutritional value, and vitamins of fresh fruit-vegetables and the combined FD product. Methods: A combination of fruits (mango, papaya, star-fruit, guava, banana, bengkuang), and vegetables (cucumber), called “Miss Freezy” were cleaned with an ozonizer and processed using the lyophilization method. The antioxidant activities measured included 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), and Hydrogen Peroxide (H2O2) assay. While the proximate analysis measured was the determination of water content, ash content, fat content, protein and carbohydrate content, and vitamin C. Results: The value of antioxidant activity in fruit-vegetable combination FD products was higher than in fresh fruit. The median inhibition concentration (IC50) of DPPH, ABTS, and H2O2 scavenging activities were guava 48.74 µg/ml, guava 128.39 µg/ml, and banana 155.55 µg/ml, respectively. The results showed that the water content of fresh fruits, and vegetables was greater than FD products and inversely proportional to the level of ash, fat, protein, carbohydrates, and vitamin C lower than FD products. Conclusions: Based on the results of antioxidant activities, proximate analysis and vitamin C of the FD product was higher than fresh fruits and vegetables. The FD fruit-vegetable combination product can be used as an alternative snack product that is practical and healthy.

Polyethylene microplastic modulates the toxicity of pentachlorophenol to the microalgae Isochrysis galbana, clone t-ISO

Pentachlorophenol (PCP) and polyethylene microplastic (PE-MP) have been designated as emerging and persistent pollutants, respectively. The combined effects of those pollutants are still unknown, especially to organisms like phytoplankton that may adsorb to their surface. Therefore, the purpose of this study was to investigate for the first time the effects of PE-MP alone and in combination with PCP on the microalgae Isochrysis galbana, clone t-ISO following 72 h of exposure. Photosynthetic pigments amounts, carotenoid, protein, carbohydrate and fatty acids have been assessed. Acute toxicity test showed that the 72 h median inhibition concentration (72 h-EC50) was 148.2, 0.66 and 087 mg L−1 for PE-MP, PCP and their mixture. The utmost effects in growth inhibition rates were noted with 0.5 and 1.25 mg L−1 PCP (23% and 85%, respectively), and 100 and 300 mg L−1 PE-MP (49% and 64%, respectively). Moreover, it was found that those concentrations had a major impact on the photosynthetic pigments, protein, carbohydrate, and fatty acids amounts in algal cells. Furthermore, levels of H2O2 and Malondialdehyde (MDA), as well as the activities of catalase (CAT), superoxide dismutase (SOD), and ascorbate peroxidase (APX), indicated the induction of an oxidative stress in algal cells. It appears that adding PE-MP at a no-effect concentration (25 mg L−1) reduces the toxicity caused by PCP due to its adsorption to polyethylene microplastics.

Quercetin has a protective impact on human umbilical vein endothelial cells against tungsten carbide cobalt nanoparticle-induced cytotoxicity, oxidative stress, apoptosis

Oxidative stress is a pivotal factor in the pathogenesis of various cancer diseases. In fact, oxidative DNA damage is described as the type of damage probably to occur in cancer cells. This study examined the protective impact of the polyphenolic compound quercetin on human umbilical vein endothelial (HUVEC) cells against tungsten carbide cobalt nanoparticles (WC-Co NPs)-induced oxidative stress, cytotoxicity, and apoptosis. One of the most often used models for studying endothelial cells in vitro is the human umbilical vein epithelial cell. Scanning electron microscope (SEM) and transmission electron microscopy (TEM) were used to measure the size of the NPs prior to WC-Co NPs treatment. WC-Co NPs had a polygonal form and measured 45.26 ± 1 nm in size. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),neutral red uptake(NRU) and lactate dehydrogenase (LDH) assays, the cytotoxicity of WC-Co NPs on HUVECs cells was assessed. The cytotoxicity of NPs increased in a concentration-dependent way. The MTT result was used to calculate the median inhibitory concentration (IC50) for HUVEC cells at 24 h, which came out to be 23.14 μg/ml. Intracellular reactive oxygen species(ROS) and lipid peroxidation(LPO) levels were elevated at 17 g/ml WC-Co NPs and then reduced in HUVECs cells upon immediate exposure to 150 µM quercetin (QR). Using JC-1 staining, the loss of mitochondrial membrane potential(MMP) in control, WC-Co NPs alone and WC-Co NPs plus QR exposed cell were evaluated. In HUVECs cells, maximum apoptotic cells were seen at increasing NPs concentrations. Based on the impacts of NPs on HUVECs cells, the data suggests that QR may work on the process of scavenging ROS, which is responsible for DNA repair. Consequently, the above findings highlight the significance of these QR as defenses against DNA damage brought on by oxidative stress, which frequently happens in a number of cancer disorders.

Elucidating the eco-friendly herbicidal potential of microbial metabolites from Bacillus altitudinis.

Microbial herbicides play a vital role in agricultural preservation, amid growing concerns over the ecological impact from extensive development and use of chemical herbicides. Utilizing beneficial microbial metabolites to combat weeds has become a significant focus of research. This study focused on isolating herbicidal active compounds from Bacillus altitudinis D30202 through activity-guided methods. First, the n-butanol extract (n-BE) of B. altitudinis D30202 underwent fractionation using macroporous adsorption resin D101 and Sephadex LH-20, identifying Fr. F as the most potent segment against wild oats (Avena fatua L.). Ultra-performance liquid chromatography - quadrupole time-of-flight mass spectrometry (UPLC - QTOF-MS) identified nine compounds in the active fraction Fr. F. Subsequently, three subfractions (Fr.F-1 to Fr.F-3) were derived from Fr.F via semi-preparative liquid chromatography, resulting in methyl indole-3-acetate (MeIAA) purification. MeIAA, functioning as an auxin analog, exhibited effects of indole-3-acetic acid (IAA) on wild oats' growth, with a root length median inhibitory concentration of 81.06µg/ml. Furthermore, we assessed MeIAA's herbicidal impact on five weed species across diverse families and genera, providing a first-time analysis of MeIAA's mechanism on wild oats. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed structural damage to leaves and roots post-MeIAA treatment. MeIAA treatment increased superoxide anion and hydrogen peroxide levels in wild oat roots, alongside with elevated peroxidase (POD) and superoxide dismutase (SOD) activity, chlorophyll-degrading enzymes (Chlase, MDACase), malondialdehyde (MDA) content, and relative conductivity in leaves. Conversely, it decreased catalase (CAT) activity and chlorophyll content. Therefore, this study provides a new material source and theoretical foundation for ecologically sustainable agricultural weed control.

Insight into the responses of the anammox granular sludge system to tetramethylammonium hydroxide (TMAH) during chip wastewater treatment

Tetramethylammonium hydroxide (TMAH), an extensively utilized photoresist developer, is frequently present in ammonium-rich wastewater from semiconductor manufacturing, and its substantial ecotoxicity should not be underestimated. This study systematically investigated the effects of TMAH on the anammox granular sludge (AnGS) system and elucidated its inhibitory mechanisms. The results demonstrated that the median inhibitory concentration of TMAH for anammox was 84.85 mg/L. The nitrogen removal performance of the system was significantly decreased after long-term exposure to TMAH (0–200 mg/L) for 30 days (p < 0.05), but it showed adaptability to certain concentrations (≤50 mg/L). Concurrently, the stability of the granules decreased dramatically, resulting in the breakdown of AnGS. Further investigations indicated that TMAH exposure increased the secretion of extracellular polymeric substances but weakened their defense function. The increase in reactive oxygen species resulted in damage to the cell membrane. Reduced activity of anammox bacteria, impeded electron transfer, and changes in enzyme activity suggested that TMAH affected the metabolic activity. Microbiological analysis revealed that TMAH caused a decrease in the abundance of anammox bacteria and a weakening of symbiotic interactions within the microbial community. These results provide valuable guidance for the AnGS system application in chip wastewater treatment.

Exploring Tryptophan-based Short Peptides: Promising Candidate for Anticancer and Antimicrobial Therapies

Background: Ultra-short peptides are essential therapeutic agents due to their heightened selectivity and reduced toxicity. Scientific literature documents the utilization of dipeptides, tripeptides, and tetrapeptides as promising agents for combating cancer. We have created a range of tryptophan-based peptides derived from literature sources in order to assess their potential as anticancer drugs. Methods: We present the results of our study on the antibacterial and anticancer effectiveness of 10 ultra-short peptides that were produced utilizing microwave-assisted solid phase peptide synthesis. The synthesized peptides underwent screening for in vitro antibacterial activity using the agar dilution method. Results: HPLC, LC-MS, 1H NMR, and 13C NMR spectroscopy were used to analyze the synthesized peptides. In tests using the HeLa and MCF-7 cell lines, the synthesized peptides' anticancer efficacy was assessed. The study found that two peptides showed potential median inhibitory concentration (IC50) values of 3.9±0.13 μM and 1.8±0.09 μM, respectively, and showed more activity than the reference medication doxorubicin. Conclusion: The antibacterial activity of synthesized peptides 3b and 4b was found to be better than the other synthetic peptides. MIC value of roughly 5–50 μg/mL for peptides 3a, 4c, and 4d showed strong antifungal activity against Candida albicans. The synthesized peptides were also evaluated for their anticancer activity against HeLa and MCF-7 cell lines, and found that peptides 3e and 4e were more potent than other peptides against doxorubicin.

Novel quinazolin-6-yl Isoindolinone: Altering polysaccharide chemstructure for antibacterial efficacy against Staphylococcus aureus

The ongoing development of novel strategies to combat Staphylococcus aureus and eliminate its biofilm formation has gained significant attention for human health. Antibiotic-resistant S. aureus necessitates the development of novel antibacterial agents with new mechanism of action. This study introduced a promising recently synthesized quinazolin-6-yl isoindolinone (IQE-X1), which exhibited potent antibacterial and antibiofilm efficacy with average median inhibitory concentration (IC50) of 3.37 μg mL−1 and minimal inhibitory concentration (MIC) of 12.5 μg mL−1, coupled with its ability to reduce cell surface hydrophobicity. IQE-X1 dose-dependently decreased extracellular polysaccharides (EPS) and its component monosaccharides, including rhamnose, arabinose, glucosamine, galactose, glucose, xylose, mannose, and ribose, accompanied by an increase in capsular polysaccharides (CP) and its individual monosaccharides, especially glucosamine. IQE-X1 demonstrated specificity in modulating the structural profiles of EPS and CP by altering the compositional ratios of their component monosaccharides. The potential mechanism of polysaccharide modulation was preliminarily elucidated through the response of β-N-acetylaminoglucosidase to IQE-X1 and their direct binding interaction. These findings provide new insights into the potential manipulation of the chemstructure of these biologically important macromolecules, EPS and CP, and highlight the antibacterial potential of IQE-X1 as a polysaccharide modulator for the development of more effective polysaccharide-targeted strategies against S. aureus.

Development of leaf-adhesive polyurethane microcapsules loaded with prochloraz for enhanced fungicide efficiency

Leaf-adhesive pesticide microcapsules represent a promising approach to improving pesticide efficacy while minimizing environmental pollution. In this study, we developed a leaf-adhesive polyurethane microcapsule loaded with prochloraz (Pro@CS-OP-10) using a reactive emulsifier (OP-10) via interfacial polymerization. Physicochemical analysis revealed microcapsules with smooth surfaces and uniform distribution, averaging 1.97 μm in size, with an encapsulation efficiency of 96.38 %. Comparative assessments demonstrated superior wetting and adhesion properties of Pro@CS-OP-10 on wheat leaves compared to other commercial formulations. Moreover, the polyurethane shell effectively enhanced the photostability of encapsulated prochloraz and hindered its rapid release. Fungal growth rate experiments indicated prolonged inhibitory effects of Pro@CS-OP-10 on Fusarium graminearum, with median inhibitory concentrations (EC50) on the second and eighth day being 0.018 mg/L and 0.045 mg/L. Therefore, the leaf-adhesive Pro@CS-OP-10 shows great potential as an environmentally friendly fungicidal formulation.

Ecotoxicological effects of triclosan on Lemna minor: bioconcentration, growth inhibition and oxidative stress.

Triclosan (TCS), an emerging pollutant, is a notable contributor to adverse impacts on aquatic organisms due to its widespread use during COVID-19 and hydrophobic properties. There is extensive documented literature on TCS toxicity in commercially important fish species; however, studies on aquatic plants remain limited. In this prelude, the present study aims to evaluate the effect of TCS on Lemna minor, a commercially important aquatic plant species for 7days. The results showed dose-dependent significant alterations in growth, pigments and stress enzymes of L. minor at varied concentrations of TCS (1 to 8mg L-1). Median inhibitory concentration (IC50) was found to be 4.813mg L-1. Total chlorophyll and carotenoid levels decreased 73.11 and 81.83%, respectively after 7days of TCS exposure. A significant increase in catalase and superoxide dismutase activity was observed in TCS exposed groups as compared to the control. Bioconcentration factor was found to be in the range of 5.855 to 37.129 signifying TCS ability to accumulate and transfer through the food chain. Scanning electron microscopy (SEM) analysis showed deformation in the cell surface and alteration of stroma morphology of TCS exposed groups. Furthermore, the Fourier transform infrared spectroscopy (FTIR) study also revealed that higher concentrations of TCS could cause alteration in the functional groups in the plant. This study demonstrates that TCS negatively impacts the growth and metabolism of primary producers, offering crucial insights into its interactions with aquatic plants and establishing baseline information essential for crafting effective mitigation strategies for TCS contamination in aquatic environments.

Three New Steroids from the Roots of Marsdenia tenacissima.

Three undescribed pregnane steroids, 12β-O-4-hydroxybenzoyl tenacigenin D (1), 12β-O-4-hydroxybenzoyl tenacigenin A (2), and 11α-nicotinoyl-17β-marsdenin (3), along with two known analogues (4 and 5), were isolated from the roots of Marsdenia tenacissima. Their structures were elucidated using one- and two-dimensional NMR, high-resolution electron ionization-mass spectrometry, single-crystal X-ray diffraction data, and experimental and density-functional-theory-calculated electronic circular dichroism measurements. All isolated compounds were evaluated for their cytotoxic activities against human lung cancer cells (A549), ovarian carcinoma cells (SKOV-3), gastric cancer cells (MGC 803) and breast cancer cells (MCF-7). Notably, 3 exhibited significant cytotoxic activity against both A549 (median inhibitory concentration (IC50) = 16.79 μM) and SKOV-3 (IC50 = 12.30 μM) cells while exhibiting moderate cytotoxicity on MGC803 and MCF-7 cells.

Comparison of Free‐Hydroxy With 3′,5′‐Di‐O‐Acetyl Ribose of 5‐Alkynyl Dicobalt Hexacarbonyl 2′‐Deoxy‐Furopyrimidines Hybrids: Synthesis, Antiproliferative Activity, and ROS Determination

ABSTRACTSynthesis of 5‐alkynyl furopyrimidine nucleoside analogs, with free‐ribose groups, was carried out, and their biological activity was evaluated. The substituents introduced at the C‐5 included propargyl and homopropargyl alcohols, 4‐methylphenyl (p‐tolyl), and 4‐pentylphenyl substituted alkynyl groups (56%–88%). Subsequently, alkyne function was coordinated to dicobalt hexacarbonyl unit, yielding the corresponding dicobalt hexacarbonyl 5‐alkynyl furopyrimidine nucleosides (51%–75%). All compounds contained 4‐pentylphenyl group attached at the C‐6 position of the bicyclic base, in line with most active antiviral structures. The antiproliferative effect of these modified nucleosides on cancer cells of different phenotypes was determined using in vitro studies. The tested compounds show antiproliferative effects with median inhibitory concentration (IC50) values of 16–23 and 9–15 μM for HeLa and K562 cells, respectively. The determination of reactive oxygen species (ROS) formation in K562 cells in the presence of modified nucleosides may suggest that the mode of action of the examined compounds may be attributed to the induction of oxidative stress.

Comparative Insecticidal Activity and Mechanism of Isocycloseram versus Other GABAergic Insecticides against the Fall Armyworm.

The fall armyworm (FAW) is a serious agricultural pest and has developed resistance to multiple insecticides. It is necessary to introduce novel insecticide(s) for controlling FAW. Isocycloseram is a completely novel isoxazoline insecticide. However, its activity and mode of action against FAW have not been reported. In this study, isocycloseram exhibited a higher insecticidal activity (LC50 = 0.26 mg/kg) than fipronil (LC50 = 7.72 mg/kg) against FAW. The median inhibitory concentration (IC50) of isocycloseram (IC50 = 8.52 nM) was almost equal to that of the desmethyl-broflanilide (IC50 = 7.32 nM) to the SfrRDL1 receptor. The IC50 of isocycloseram to the SfrRDL2 receptor was 11.13 nM, which was obviously less than that of desmethyl-broflanilide, dieldrin, fipronil, fluxametamide. Compared with the SfrRDL2 receptor, the SfrRDL1 receptor exhibited higher sensitivity to GABAergic insecticides. The recombinant SfrGluCl receptor was successfully stimulated by l-glutamate; however, the currents were low and weakly inhibited by isocycloseram at 10 μM. In conclusion, our results provided the theoretical basis for usage of GABAergic insecticides for controlling FAW.

Telomerase related molecular subtype and risk model reveal immune activity and evaluate prognosis and immunotherapy response in prostate cancer

BackgroundProstate cancer ranks among the six most lethal malignancies worldwide. Telomerase, a reverse transcriptase enzyme, plays a pivotal role in extending cellular telomeres and is intimately associated with cell proliferation and division. However, the interconnection between prostate cancer and telomerase-related genes (TEASEs) remains unclear.MethodsSomatic mutations and copy number alterations of TEASEs were comprehensively analyzed. Subsequently, the transcripts of prostate cancer patients in TCGA and GEO databases were integrated to delineate new molecular subtypes. Followed by constructing a risk model containing nine characteristic genes through Lasso regression and Cox prognostic analysis among different subtypes. Various aspects including prognosis, tumor microenvironment (TME), landscape of immunity, tumor mutational burden (TMB), stem cell correlation, and median inhibitory concentration amongst different risk groups were compared. Finally, the expression, prognosis, and malignant biological behavior of ZW10 interactor (ZWINT) in vitro was explored.ResultsTEASEs exhibited a notably high mutation frequency. Three distinct molecular subtypes and two gene subclusters based on TEASEs were delineated, displaying significant associations with prognosis, immune function regulation, and clinical characteristics. Low-risk patients demonstrated superior prognosis and better response to immunotherapy. Conversely, high-risk patients exhibited higher TMB and stronger stem cell correlations. It was also found that the patients’ sensitivity to chemotherapy agents was impacted by the risk score. Finally, ZWINT’s potential as a novel diagnostic and prognostic biomarker for prostate cancer was validated.ConclusionsTEASEs play a pivotal role in modulating immune regulation and immunotherapeutic responses, thereby significantly impacting the diagnosis, prognosis, and treatment strategies for affected patients.

Biocontrol Mechanisms of Three Plant Essential Oils Against Phytophthora infestans Causing Potato Late Blight.

Late blight, caused by the notorious pathogen Phytophthora infestans, poses a significant threat to potato (Solanum tuberosum) crops worldwide, impacting their quality as well as yield. Here, we aimed to investigate the potential use of cinnamaldehyde, carvacrol, and eugenol as control agents against P. infestans and to elucidate their underlying mechanisms of action. To determine the pathogen-inhibiting concentrations of these three plant essential oils (PEOs), a comprehensive evaluation of their effects using gradient dilution, mycelial growth rate, and spore germination methods was carried out. Cinnamaldehyde, carvacrol, and eugenol were capable of significantly inhibiting P. infestans by hindering its mycelial radial growth, zoospore release, and sporangium germination; the median effective inhibitory concentration of the three PEOs was 23.87, 8.66, and 89.65 μl/liter, respectively. Scanning electron microscopy revealed that PEOs caused the irreversible deformation of P. infestans, resulting in hyphal shrinkage, distortion, and breakage. Moreover, propidium iodide staining and extracellular conductivity measurements demonstrated that all three PEOs significantly impaired the integrity and permeability of the pathogen's cell membrane in a time- and dose-dependent manner. In vivo experiments confirmed the dose-dependent efficacy of PEOs in reducing the lesion diameter of potato late blight. Altogether, these findings provide valuable insight into the antifungal mechanisms of PEOs vis-à-vis late blight-causing P. infestans. By utilizing the inherent capabilities of these natural compounds, we could effectively limit the harmful impacts of late blight on potato crops, thereby enhancing agricultural practices and ensuring the resilience of global potato food production.

Evaluation of the Antioxidant and Anti-Inflammatory Activities and Acute Toxicity of Caco Seed (Chrysobalanus icaco L.) in Murine Models.

Chysobalanus icaco L. (C. icaco) is a plant that is native to tropical America and Africa. It is also found in the southeast region of Mexico, where it is used as food and to treat certain diseases. This study aimed to carry out a phytochemical analysis of an aqueous extract of C. icaco seed (AECS), including its total phenol content (TPC), total flavonoid content (TFC), and condensed tannins (CT). It also aimed to examine the antioxidant and metal-ion-reducing potential of the AECS in vitro, as well as its toxicity and anti-inflammatory effect in mice. Antioxidant and metal-ion-reducing potential was examined by inhibiting DPPH, ABTS, and FRAP. The acute toxicity test involved a single administration of different doses of the AECS (0.5, 1, and 2 g/kg body weight). Finally, a single administration at doses of 150, 300, and 600 mg/kg of the AECS was used in the carrageenan-induced model of subplantar acute edema. The results showed that the AECS contained 124.14 ± 0.32 mg GAE, 1.65 ± 0.02 mg EQ, and 0.910 ± 0.01 mg of catechin equivalents/g dried extract (mg EC/g de extract) for TPC, TFC and CT, respectively. In the antioxidant potential assays, the values of the median inhibition concentration (IC50) of the AECS were determined with DPPH (0.050 mg/mL), ABTS (0.074 mg/mL), and FRAP (0.49 mg/mL). Acute toxicity testing of the AECS revealed no lethality, with a median lethal dose (LD50) value of >2 g/kg by the intragastric route. Finally, for inhibition of acute edema, the AECS decreased inflammation by 55%, similar to indomethacin (59%, p > 0.05). These results demonstrated that C. icaco seed could be considered a source of bioactive molecules for therapeutic purposes due to its antioxidant potential and anti-inflammatory activity derived from TPC, with no lethal effect from a single intragastric administration in mice.

Design, synthesis and biological evaluation of aloperine derivatives as potential anticancer agents

Modifications at different positions on the aloperine molecule were performed to improve its anticancer activity and develop anticancer drugs. The in vitro anticancer activities of 44 synthesized compounds were evaluated. The effect of modification positions on anticancer activity was discussed and a structure–activity relationship analysis was established. A novel series of compounds with modifications at the N12 position showed much higher cytotoxicity than aloperine. Among them, compound 22 displayed promising in vitro anticancer activity against PC9 cells with a median inhibitory concentration (IC50) of 1.43 μM. The mechanism studies indicated that compound 22 induced cell apoptosis and cell cycle arrest in PC9 cells. These results demonstrate the potential of aloperine thiourea derivatives in anticancer activity.

Spray-drying and ultrasonication processing of camel whey protein concentrate: Characterization and impact on bioactive properties

The production of whey protein concentrates (WPC) from camel milk whey represents an effective approach to valorize this processing byproduct. These concentrates harbor active ingredients with significant bioactive properties. Camel WPC were spray-dried at inlet temperature of 170, 185 and 200°C, or ultrasonicated (US) for 5, 10, and 15 min, then freeze-dried to obtain fine powder. The effect of both treatments on protein degradation was studied by sodium dodecyl sulfate-PAGE and reverse-phase ultraperformance liquid chromatography techniques. Significantly Substantially enhanced protein degradation was observed after US treatment when compared with spray-drying (SPD). Both SPD and US treatments slightly enhanced the WPC samples' antioxidant activities. The US exposure for 15 min exhibited the highest 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity (12.12 mmol Trolox equivalent per gram). Moreover, US treatment for 10 min exhibited the highest in vitro antidiabetic properties (α-amylase and α-glucosidase inhibition), and dipeptidyl peptidase-IV inhibitory activity among all samples. In addition, the US for 10 min and SPD at 170°C showed the lowest median inhibitory concentration (IC50) values for in vitro antihypercholesterolemic activities in terms of pancreatic lipase and cholesteryl esterase inhibition. Conclusively, these green techniques can be adapted in the preservation and processing of camel milk whey into active ingredients with high bioactive properties.

Effects of Cadmium and Nickel Mixtures on Multiple Endpoints of the Microalga Raphidocelis subcapitata.

It is crucial to investigate the effects of mixtures of contaminants on aquatic organisms, because they reflect what occurs in the environment. Cadmium (Cd) and nickel (Ni) are metals that co-occur in aquatic ecosystems, and information is scarce on their joint toxicity to Chlorophyceae using multiple endpoints. We evaluated the effects of isolated and combined Cd and Ni metals on multiple endpoints of the chlorophycean Raphidocelis subcapitata. The results showed that Cd inhibited cell density, increased reactive oxygen species (ROS) production (up to 308% at 0.075 mg L-1 of Cd), chlorophyll a (Chl a) fluorescence (0.050-0.100 mg L-1 of Cd), cell size (0.025-0.100 mg L-1 of Cd), and cell complexity in all concentrations evaluated. Nickel exposure decreased ROS production by up to 25% at 0.25 mg L-1 of Ni and Chl a fluorescence in all concentrations assessed. Cell density and oxygen-evolving complex (initial fluorescence/variable fluorescence [F0/Fv]) were only affected at 0.5 mg L-1 of Ni. In terms of algal growth, mixture toxicity showed antagonism at low doses and synergism at high doses, with a dose level change greater than the median inhibitory concentration. The independent action model and dose-level-dependent deviation best fit our data. Cadmium and Ni mixtures resulted in a significant increase in cell size and cell complexity, as well as changes in ROS production and Chl a fluorescence, and they did not affect the photosynthetic parameters. Environ Toxicol Chem 2024;43:1855-1869. © 2024 SETAC.

MmpR5 protein truncation and bedaquiline resistance in Mycobacterium tuberculosis isolates from South Africa: a genomic analysis

The antibiotic bedaquiline is a key component of new WHO regimens for drug-resistant tuberculosis; however, predicting bedaquiline resistance from bacterial genotypes remains challenging. We aimed to understand the genetic mechanisms of bedaquiline resistance by analysing Mycobacterium tuberculosis isolates from South Africa. For this genomic analysis, we conducted whole-genome sequencing of Mycobacterium tuberculosis samples collected at two referral laboratories in Cape Town and Johannesburg, covering regions of South Africa with a high prevalence of tuberculosis. We used the tool ARIBA to measure the status of predefined genes that are associated with bedaquiline resistance. To produce a broad genetic landscape of M tuberculosis in South Africa, we extended our analysis to include all publicly available isolates from the European Nucleotide Archive, including isolates obtained by the CRyPTIC consortium, for which minimum inhibitory concentrations of bedaquiline were available. Between Jan 10, 2019, and July, 22, 2020, we sequenced 505 M tuberculosis isolates from 461 patients. Of the 64 isolates with mutations within the mmpR5 regulatory gene, we found 53 (83%) had independent acquisition of 31different mutations, with a particular enrichment of truncated MmpR5 in bedaquiline-resistant isolates resulting from either frameshift mutations or the introduction of an insertion element. Truncation occurred across three Mtuberculosis lineages, and were present in 66% of bedaquiline-resistant isolates. Although the distributions overlapped, the median minimum inhibitory concentration of bedaquiline was 0·25 mg/L (IQR 0·12-0·25) in mmpR5-disrupted isolates, compared with 0·06 mg/L (0·03-0·06) in wild-type M tuberculosis. Reduction in the susceptibility of M tuberculosis to bedaquiline has evolved repeatedly across the phylogeny. In our data, we see no evidence that this reduction has led to the spread of a successful strain in South Africa. Binary phenotyping based on the bedaquiline breakpoint might be inappropriate to monitor resistance to this drug. We recommend the use of minimum inhibitory concentrations in addition to MmpR5 truncation screening to identify moderate increases in resistance to bedaquiline. US Centers for Disease Control and Prevention.