Median Inhibitory Concentration Research Articles

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.

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.

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.

An electrochemiluminescent dual-signal immunosensor based on a Ru(bpy)32+-doped silica nanoparticle/copper nanocluster composite for okadaic acid detection

In this study, a sensitive dual-signal electrochemiluminescence (ECL) immunosensor was developed for okadaic acid (OA) detection utilizing copper nanoclusters (CuNCs) and Ru(bpy)32+-doped silica nanoparticles (RuSiNPs). Interestingly, the CuNCs could simultaneously enhance both cathodic (−0.95 V) and anodic (+1.15 V) ECL signals of RuSiNPs, forming a dual-signal ECL sensing platform. Further, RuSiNPs@CuNCs were used as immunomarkers by covalently conjugating them with an anti-OA monoclonal antibody (mAb) to form probes. Finally, dual ECL signals of the immunosensor were fabricated and showed good linear relationships with OA concentrations in the range of 0.05–70 ng mL−1, having a median inhibitory concentration (IC50) of 1.972 ng mL−1 and a limit of detection of 0.039 ng mL−1. Moreover, the constant ratio of the cathodic and anodic ECL peaks achieved self-calibration of the detection signal and improved the reliability of the results. Finally, we successfully applied the ECL sensor to detect OA in spiked oyster samples.

Purpurogallin carboxylic acid exhibits synergistic effects with 5‑fluorouracil on liver cancer cells in vitro by targeting ABCG2.

Purpurogallin carboxylic acid (PCA) is a natural phenol compound derived from Macleaya microcarpa (Maxim.) Fedde, which exerts particular antioxidant and anti-inflammatory capacities. However, the effects and mechanisms of PCA on liver cancer cells remain unknown. Therefore, network pharmacology and computer virtual docking were used to identify the target-proteins of PCA. In addition, surface plasmon resonance, protease activity and rhodamine excretion assays were carried out to evaluate the effects of PCA on the activity of ATP binding cassette subfamily G member 2 (ABCG2). The synergistic effects of PCA and 5-fluorouracil (5-FU) on liver cancer cell proliferation, cell cycle arrest, colony formation and spheroid formation abilities in vitro were determined by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, western blot analysis, colony formation and spheroid formation assays, respectively. ABCG2 was identified as a potential target of PCA, with a high docking score. The equilibrium dissociation constant of PCA for ABCG2 protein was 1.84 µM, while the median inhibitory concentration of this protein was 3.09 µM. In addition, the results demonstrated that PCA could significantly reduce the drug efflux capacity of liver cancer cells. CCK-8 assays revealed that liver cancer cell treatment with 10 µM PCA and 10 µM 5-FU exhibited the most potent synergistic effects on liver cancer cell proliferation at 48 h. Additionally, cell co-treatment with PCA and 5-FU also significantly attenuated the colony and spheroid formation abilities of liver cancer cells in vitro, while it promoted their arrest at the G1 phase of the cell cycle. Furthermore, ABCG2 silencing in liver cancer cells notably abrogated the synergistic effects of PCA and 5-FU. In conclusion, the present study demonstrated that PCA exhibited synergistic effects with 5-FU on liver cancer cells in vitro via targeting ABCG2. Therefore, PCA combined with 5-FU may be a potential strategy for liver cancer therapy.

Design, synthesis, antifungal evaluation and mechanism study of novel norbornene derivatives as potential laccase inhibitors.

To discover novel fungicide candidates, five series of novel norbornene hydrazide, bishydrazide, oxadiazole, carboxamide and acylthiourea derivatives (2a-2t, 3a-3f, 4a-4f, 5a-5f and 7a-7f) were designed, synthesized and assayed for their antifungal activity toward seven representative plant fungal pathogens. In the in vitro antifungal assay, some title norbornene derivatives presented good antifungal activity against Botryosphaeria dothidea, Sclerotinia sclerotiorum and Fusarium graminearum. Especially, compound 2b exhibited the best inhibitory activity toward B. dothidea with the median effective concentration (EC50) of 0.17 mg L-1, substantially stronger than those of the reference fungicides boscalid and carbendazim. The in vivo antifungal assay on apples revealed that 2b had significant curative and protective effects, both of which were superior to boscalid. In the preliminary antifungal mechanism study, 2b was able to injure the surface morphology of hyphae, destroy the cell membrane integrity and increase the intracellular reactive oxygen species (ROS) level of B. dothidea. In addition, 2b could considerably inhibit the laccase activity with the median inhibitory concentration (IC50) of 1.02 μM, much stronger than that of positive control cysteine (IC50 = 35.50 μM). The binding affinity and interaction mode of 2b with laccase were also confirmed by molecular docking. This study presented a promising lead compound for the study of novel laccase inhibitors as fungicidal agrochemicals, which demonstrate significant anti-B. dothidea activity and laccase inhibitory activity. © 2024 Society of Chemical Industry.

Protective effect of Ganoderma lucidum-fermented crop extracts against hydrogen peroxide- or β-amyloid-induced damage in human neuronal SH-SY5Y cells

BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of stacked β-amyloid peptides in the brain and associated with the generation of oxidative stress. So far, there is no cure for AD or a way to stop its progression. Although the neuroprotective effects of Ganoderma lucidum aqueous extract and G. lucidum-derived triterpenoids and polysaccharides have been reported, the influence of G. lucidum-fermented crops on AD still lacks clarity.MethodsThis study aimed to investigate the protective effect of G. lucidum-fermented crop extracts against hydrogen peroxide- or β-amyloid peptide (Aβ25-35)-induced damage in human neuroblastoma SH-SY5Y cells.ResultsVarious extracts of G. lucidum-fermented crops, including extract A: 10% ethanol extraction using microwave, extract B: 70˚C water extraction, and extract C: 100˚C water extraction followed by ethanol precipitation, were prepared and analyzed. Extract B had the highest triterpenoid content. Extract C had the highest total glucan content, while extract A had the highest gamma-aminobutyric acid (GABA) content. The median inhibitory concentration (IC50, mg/g) for DPPH and ABTS scavenging activity of the fermented crop extracts was significantly lower than that of the unfermented extract. Pretreatment with these extracts significantly increased the cell viability of SH-SY5Y cells damaged by H2O2 or Aβ25-35, possibly by reducing cellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Moreover, extract B markedly alleviated the activity of acetylcholinesterase (AChE), which is crucial in the pathogenesis of AD.ConclusionThese results clearly confirmed the effects of G. lucidum-fermented crop extracts on preventing against H2O2- or Aβ25-35-induced neuronal cell death and inhibiting AChE activity, revealing their potential in management of AD.

Preparation of limonin monoclonal antibody and establishment of a sensitive icELISA for analyzing limonin in citrus and herbal samples

Limonin is an intensely bitter and highly oxidized tetracyclic triterpenoid secondary metabolite, which is abundant in the Rutaceae and Meliaceae, especially in Citrus. In order to detect limonin content in complex substrates such as citrus and traditional Chinese medicine, monoclonal antibodies specifically recognizing limonin were prepared and an indirect competitive enzyme-linked immunosorbent assay (icELISA) was established. The median inhibition concentration (IC50) was 5.40 ng/mL and the linear range was 1.25–23.84 ng/mL. The average recoveries from citrus peel and pulp samples were 95.9%–118.8% and 77.5%–113.1%, respectively. Moreover, the contents of limonin in 6 citrus samples and 4 herbal samples were analyzed by icELISA and UPLC-MS, and the results of the two methods were consistent. This validation is sufficient to demonstrate that the developed immunoassay is applicable for the detection of limonin in citrus and herbal samples and has the advantage of high efficiency, sensitivity, and convenience.

Comprehensive analysis of exosome gene LYPD3 and prognosis/immune cell infiltration in lung cancer.

Lung cancer (LC) is a leading cause of cancer-associated mortality worldwide, with high incidence and mortality rates. Ly6/PLAUR domain containing 3 (LYPD3) is a tumorigenic and highly glycosylated cell surface protein that has been rarely reported in LC. This study aimed to explore the prognostic role and immune cell infiltration of LYPD3 in LC. We used ExoCarta, a database of exosomal proteins and RNA, to select exosomes in LC. The Tumor Immune Estimation Resource (TIMER) and Human Protein Atlas (HPA) databases were utilized to compare the expression of LYPD3 in LC. We applied Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (KM) plotter to evaluate the prognostic prediction performance of LYPD3. Biological processes (BPs), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and gene set enrichment analysis (GSEA) analyses were performed to illustrate the possible role of LYPD3 in LC. The correlations between LYPD3 and immune cell infiltration were explored using Tumor and Immune System Interaction Database (TISIDB), GEPIA2, and TIMER. R software was used for statistical analysis and mapping. A total of 904 exosome molecules were screened in LC. Further analysis showed that the up-regulation of LYPD3 in these 904 exosome molecules was associated with poor prognosis in LC. Pan-cancer analyses revealed that the expression of LYPD3 varied in many cancers, particularly in LC. Clinical correlation analysis indicated that LYPD3 was associated with stage and T classification in LC. We observed that LYPD3 co-expression genes were associated with cell cycle, DNA replication, proteasome, and regulation of the actin cytoskeleton by GSEA. Moreover, LYPD3 was associated with immune modulators. Immunophenoscores (IPS) and IPS-CTLA4 were significantly different between the high LYPD3 group and low LYPD3 group. Additionally, the median half maximal inhibitory concentration (IC50) of bexarotene, cyclopamine, etoposide, and paclitaxel in LYPD3 high group was significantly lower than that in LYPD3 low group. LYPD3 is involved in many BPs of LC, such as regulating immune cell infiltration and affecting prognosis. Therefore, LYPD3 may have potential value as a biomarker for prognosis and immunotherapy in LC.

Identification of Trichderma harzianum in postharvest Agaricus bisporus and a novel control approach using eucalyptus essential oil emulsion

Pathogenic infections have been a key factor leading to mushroom deterioration. However, few studies have focused on the isolation, identification, and control of pathogens causing infections in mushroom. In this study, the Trichoderma harzianum strain TPS2 was screened from the tissues of infected Agaricus bisporus. To inhibit the pathogenic microorganism, the eucalyptus essential oil (EEO)-tamarind gum (TG) emulsion was prepared and its antimicrobial mechanism and preservative effect of postharvest Agaricus bisporus were explored through emulsion fumigation. According to the in vitro experiment results, the EEO-TG emulsion induced the accumulation of reactive oxygen species, lipid peroxidation of the cell membrane, and destruction of cell membrane integrity. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results further revealed that the EEO-TG emulsion damaged the membrane permeability of T. harzianum, thereby resulting in the increased leakage of mycelial cell contents and achieving the antimicrobial effect. As the essential oil concentration in the EEO-TG emulsion increased, the effect on T. harzianum intensified. The ratio of EEO to TG at 1:10 was the minimum inhibitory concentration (MIC100), and the median inhibitory concentration (MIC50) was 1:40. In situ experiments, mushrooms fumigated with the EEO-TG emulsion exhibited high firmness, high whiteness, low electrical conductivity, and low weight loss, along with effective inhibition of the respiratory intensity and reduction in the excessive loss of nutrients. Therefore, the EEO-TG emulsion is of great significance in preventing postharvest diseases symptoms and delaying the senescence of mushrooms.

Are carfentanil and acrylfentanyl naloxone resistant?

The rapid rise in deaths since 2012 due to opioid poisoning is correlated with the proliferation of potent synthetic opioid agonists such as fentanyl, acrylfentanyl, and carfentanil. The efficacy of frontline antidotes such as naloxone in reversing such poisoning events has been questioned, and the possibility of naloxone-resistant synthetic opioids has been raised. In this manuscript, we applied in vitro techniques to establish the median effective inhibitory concentrations for fentanyl, acrylfentanyl, and carfentanil and subsequently evaluate naloxone's ability to reverse agonist-receptor interactions.

Steroid Drugs Inhibit Bacterial Respiratory Oxidases and Are Lethal Toward Methicillin-Resistant Staphylococcus aureus.

Cytochrome bd complexes are respiratory oxidases found exclusively in prokaryotes that are important during infection for numerous bacterial pathogens. In silico docking was employed to screen approved drugs for their ability to bind to the quinol site of Escherichia coli cytochrome bd-I. Respiratory inhibition was assessed with oxygen electrodes using membranes isolated from E. coli and methicillin-resistant Staphylococcus aureus strains expressing single respiratory oxidases (ie, cytochromes bd, bo', or aa3). Growth/viability assays were used to measure bacteriostatic and bactericidal effects. The steroid drugs ethinylestradiol and quinestrol inhibited E. coli bd-I activity with median inhibitory concentration (IC50) values of 47 ± 28.9 µg/mL (158 ± 97.2 µM) and 0.2 ± 0.04 µg/mL (0.5 ± 0.1 µM), respectively. Quinestrol inhibited growth of an E. coli "bd-I only" strain with an IC50 of 0.06 ± 0.02 µg/mL (0.2 ± 0.07 µM). Growth of an S. aureus "bd only" strain was inhibited by quinestrol with an IC50 of 2.2 ± 0.43 µg/mL (6.0 ± 1.2 µM). Quinestrol exhibited potent bactericidal effects against S. aureus but not E. coli. Quinestrol inhibits cytochrome bd in E. coli and S. aureus membranes and inhibits the growth of both species, yet is only bactericidal toward S. aureus.

Chemical composition and antimicrobial activity of essential oil of Alpinia menghaiensis S.Q. Tong & Y.M. Xia in S.Q. Tong from Vietnam

The chemical constituents and antimicrobial activity of the essential oil isolated from the rhizomes of Alpinia menghaiensis S.Q. Tong & Y.M. Xia in S.Q. Tong from Vietnam was studied and reported. The techniques of gas chromatography (GC) and gas chromatography coupled with mass spectrometry (GC/MS) were used to characterize the chemical constituents of the essential oil while the microdilution assay was used to evaluate the antimicrobial activity. The main compounds identified in the rhizome essential oil consist of β-pinene (46.5%), β-phellandrene (25.7%) and α-pinene (8.5%). The studied essential oil inhibited the growth of Pseudomonas aeruginosa ATCC27853 with minimum inhibitory concentrations (MIC) value of 15.32 μg/mL ±0.01, and median inhibitory concentration (IC50) value of 32.0 ±0.01 μg/mL. The essential oil also displayed activity against Staphylococcus aureus ATCC25923 (MIC 31.57 ±0.01 μg/mL) and Bacillus cereus ATCC14579 (MIC, 34.21 μg/mL ±0.01 μg/mL), and IC50 value of 64.0 ±0.01 μg/mL. This is the first report on the rhizome oil composition, as well as the antimicrobial of essential oils from A. menghaiensis. The paper discusses further the comparative analysis of essential oils from A. menghaiensis.

Bioflocculation of pollutants in wastewater using flocculant derived from Providencia huaxiensis OR794369.1

BackgroundWater pollution has become a major environmental and health concern due to increasing population and industrialisation. Microbial flocculants are promising agents for treatment of contaminated water owing to their effectiveness, eco-friendliness, and high biosafety levels. In this study, culture conditions of Providencia huaxiensis OR794369.1 were optimised and its bioflocculant was extracted, characterised and used to treat wastewater.ResultsThe maximum flocculating activity of 92% and yield of 3.5 g/L were obtained when cultivation conditions were: 3% inoculum size, starch, casein, initial pH of 6, cultivation temperature of 30 oC and 72 h of fermentation. The bioflocculant is an amorphous glycoprotein biomolecule with 37.5% carbohydrates, 27.9% protein, and 34.6% uronic acids. It is composed of hydroxyl, amino, alkanes, carboxylic acid and amines groups as its main functional structures. It was found to be safe to use as it demonstrated non-cytotoxic effects on bovine dermis and African green monkey kidney cells, illustrating median inhibitory concentration (IC50) values of 180 and > 500 µg/mL on both cell lines, respectively. It demonstrated the removal efficiencies of 90% on chemical oxygen demand (COD), 97% on biological oxygen demand (BOD) and 72% on Sulphur on coal mine wastewater. It also revealed the reduction efficacies of 98% (COD) and 92% (BOD) and 70% on Sulphur on domestic wastewater.ConclusionThe bioflocculant was effective in reducing pollutants and thus, illustrated potential to be used in wastewater treatment process as an alternative.

PH-responsive degradable mesoporous organosilica nanoparticle for tumor targeting and phototherapy combined with chemotherapy

In the context of the tumor microenvironment, the design of a high concentration glutathione (GSH) driven degradation drug delivery system (ID@MON-HA) is according to a different quantity of GSH to normal tissues. This system involves loading doxorubicin (DOX) and new indocyanine green (IR820) onto mesoporous organosilica nanoparticles (MON). The disulfide linkages in MON are broken in response to high amounts of GSH in tumor cells, resulting in the degradation of the overall structure and preventing carrier accumulation. To connect the hyaluronic acid (HA) and the carrier with encapsulated drugs, a pH-sensitive Schiff based bond is utilized. Furthermore, MON specifically target to tumor sites due to the selective binding of HA to tumor cells that overexpress the CD44 receptor. Experiments have shown that increased GSH concentrations and pH levels below physiological can accelerate drug release. Additionally, in vitro cellular experiments have demonstrated that combining chemotherapy and phototherapy enhances the suppression of tumor cells (median inhibition concentration IC50 = 1.53 μg mL_1). These findings indicate that the study offers an acceptable approach for developing degradable nanoplatforms for tumor combination therapy.

Identification of natural xanthine oxidase inhibitors: Virtual screening, anti-xanthine oxidase activity, and interaction mechanism

Xanthine oxidase (XO) is a crucial target for hyperuricemia treatment(s). Naturally occurred XO inhibitors with minimal toxicity and high efficacy have attracted researchers' attention. With the goal of quickly identifying natural XO inhibitors, an integrated computational screening strategy was constructed by molecular docking and calculating the free energy of binding. Twenty-seven hits were achieved from a database containing 19,377 natural molecules. This includes fourteen known XO inhibitors and four firstly-reported inhibitors (isolicoflavonol, 5,7-dihydroxycoumarin, parvifolol D and clauszoline M, IC50 < 40 μM). Iolicoflavonol (hit 8, IC50 = 8.45 ± 0.68 μM) and 5,7-dihydroxycoumarin (hit 25, IC50 = 10.91 ± 0.71 μM) displayed the great potency as mixed-type inhibitors. Docking study and molecular dynamics simulation revealed that both hits could interact with XO's primarily active site residues ARG880, MOS1328, and ASN768 of XO. Fluorescence spectroscopy studies showed that hit 8 bound to the active cavity region of XO, causing changes in XO's conformation and hydrophobicity. Hits 8 and 25 exhibit favorable Absorption, Distribution, Metabolism, and Excretion (ADME) properties. Additionally, no cytotoxicity against human liver cells was observed at their median inhibition concentrations against XO. Therefore, the present study offers isolicoflavonol and 5,7-dihydroxycoumarin with the potential to be disease-modifying agents for hyperuricemia.

Chemical composition, antimicrobial and larvicidal activities of essential oils of two Syzygium species from Vietnam.

The present study is the first to investigate the chemical composition, antimicrobial and larvicidal activities of the essential oils from the leaves of Syzygium attopeuense (Gagnep.) Merr. & L.M.Perry and Syzygium tonkinense (Gagnep.) Merr. & L.M.Perry collected in Vietnam. The essential oils were extracted by hydrodistillation and analyzed by GC and GC-MS. The study indicated the presence of a high percentage of sesquiterpenes in both investigated essential oils. The major components of S. attopeuense essential oil were bicyclogermacrene (24.26%), (E)-caryophyllene (11.72%), and (E)-β-ocimene (6.75%), whereas S. tonkinense essential oil was dominated by (E)-caryophyllene (80.80%). The antimicrobial activity of essential oils was evaluated by broth microdilution assay to determine the minimum inhibitory concentration (MIC) and median inhibitory concentration (IC50). Both essential oils exhibited remarkable inhibitory activity against all tested Gram-positive bacteria and yeast than Gram-negative bacteria. Among them, essential oils of S. attopeuense and S. tonkinense possessed the strongest activity against Enterococcus faecalis (MIC = 4.00 μg/mL; IC50 = 1.69 μg/mL) and Candida albicans (MIC = 16.00 μg/mL; IC50 = 8.67 μg/mL), respectively. Furthermore, the larvicidal activity of essential oils was tested using fourth-instar larvae of Aedes aegypti. Results from the larvicidal test revealed that both essential oils had an excellent inhibitory effect against A. aegypti larvae with LC50 values from 25.55 to 30.18 μg/mL and LC90 values from 33.00 to 39.01 μg/mL. Our findings demonstrate that the essential oil extracted from S. attopeuense and S. tonkinense are potential sources of natural antimicrobials and can act as inexpensive mosquito larvicidal agents.