Strong Activity Research Articles

Hypothesis of a CD137/Eomes activating axis for effector T cells in HPV oropharyngeal cancers

Chronic Human Papilloma Virus (HPV) infection is supplanting alcohol and tobacco intoxications as the leading cause of oropharyngeal cancer in developed countries. HPV-related squamous cell carcinomas of the oropharynx (HPV + OSC) present better survival and respond better to radiotherapy and chemotherapy. Regulatory T cells (TREG) are mainly described as immunosuppressive and protumoral in most solid cancers. However, TREG are paradoxically associated with a better prognosis in HPV + OSCs. The transcription factor FoxP3 is the basis for the identification of TREG. Among CD4 + FoxP3 + T cells, some have effector functions. A medical hypothesis is formulated here: the existence of a CD137 (4.1BB)-Eomesodermin (Eomes) activated pathway downstream of TCR-specific activation in a subpopulation of CD4 + FoxP3 + T cells may explain this effector function. Evidence suggest that this axis may exist either in CD4 + FoxP3 + T cells or CD8 + T cells. This pathway could lead T cells to strong antitumor cytotoxic activity in a tumor-specific manner. Furthermore, CD137 is one of the most expected targets for the development of agonist immunotherapies. The identification of CD137 + Eomes + FoxP3+/- T cells could be a key element in the selective activation of the most anti-tumor cells in the HPV + OSC microenvironment.

Green and efficient radiation-based preparation of crosslinked poly(vinyl pyrrolidone)-iodine (PVP-I)-introduced polypropylene (PP) sheets for antibacterial wound dressing application

In this study, we developed an efficient method to prepare a crosslinked poly(vinyl pyrrolidone)/poly(ethylene glycol) diacrylate) (PVP/PEGDA) copolymer-grafted non-woven polypropylene (PP) sheet for which water can be used as a green solvent while providing a large amount of grafting functional groups on the PP matrix without diminishing mechanical properties. It was demonstrated that subsequent iodine complexation of the PP-g-PVP/PEGDA produces a strong antibacterial activity desirable for wound dressings. Efficient functionalization of hydrophobic non-woven PP sheet was achieved using electron beam (EB)-induced graft polymerization of vinyl pyrrolidone (VP) with the addition of hydrophilic crosslinker (PEGDA), resulting in the PP-g-PVP/PEGDA. In this preparation method, the grafting degree was remarkably increased up to 3-fold, even in the water solvent, and was found to be controlled by the concentration of VP and PEGDA. To impart antibacterial activity, the PP-g-PVP/PEGDA subsequently underwent iodine complexation, yielding PP-g-PVP/PEGDA-I. Structural analysis and water absorptivity studies confirmed that excellent water-absorbing PVP/PEGDA-I complexes were successfully introduced in the non-woven PP sheet without significant change in the porous structure of the PP sheet. Moreover, the PP-g-PVP/PEGDA-I exhibited strong antibacterial activities against Gram-negative E. coli, Gram-positive S. aureus, and MRSA bacterial species in a time-killing assay, and the activities showed high dependence on the grafting degree. This finding demonstrates that the PP-g-PVP/PEGDA-I can effectively and immediately inactivate external bacteria upon invasion. This green and efficient strategy is thus promising to produce PVP-I complex-based wound dressings with rapid antibacterial activity.

Zebrafish ANGPT4, member of fibrinogen-related proteins, is an LTA-, LPS- and PGN-binding protein with a bacteriolytic activity

Fibrinogen-related proteins (FREPs) are a family of glycoproteins that contain a fibrinogen-like (FBG) domain. Many members of FREPs have been shown to play an important role in innate immune response in both vertebrates and invertebrates. Here we reported the immune functional characterization of ANGPT4, member of FREPs, in zebrafish Danio rerio. Quantitative real time PCR showed that the expression of zebrafish ANGPT4 gene is up-regulated by the challenge with lipoteichoic acid (LTA) or lipopolysaccharides (LPS), hinting its involvement in innate immune response. The recombinant ANGPT4 (rANGPT4) could bind to both gram-positive bacteria Staphylococcus aureus and Bacillus subtilis and the gram-negative bacteria Escherichia coli and Aeromonas hydrophila as well as the pathogen-associated molecular patterns (PAMPs) on the bacterial surfaces including LTA, LPS and peptidoglycan (PGN), suggesting it capable of identifying pathogens via LTA, LPS and PGN. In addition, rANGPT4 also displayed strong bacteriolytic activities against both gram-positive and -negative bacteria tested via inducing membrane depolarization and intracellular ROS production. Moreover, the bacterial clearance assay in vivo showed that the rANGPT4 could also accelerate the clearance of bacteria in zebrafish embryos/larvae. Finally, we showed that the eukaryotically expressed recombinant ANGPT4 maintained antibacterial activity and binding activity to bacteria and LTA, LPS and PGN. All these suggested that ANGPT4 could not only capable of recognizing pathogens via LTA, LPS and PGN, but also capable of killing the Gram-positive and Gram-negative bacteria, in innate immune response. This work also provides further information to understand the biological roles of FREPs and the innate immunity in vertebrates.

Ethanolic extract from fruiting bodies of Cordyceps militaris HL8 exhibits cytotoxic activities against cancer cells, skin pathogenic yeasts, and postharvest pathogen Penicillium digitatum.

Cordyceps militaris is a well-known medicinal mushroom in Asian countries. This edible fungus has been widely exploited for traditional medicine and functional food production. C. militaris is a heterothallic fungus that requires both the mating-type loci, MAT1-1 and MAT1-2, for fruiting body formation. However, recent studies also indicated two groups of C. militaris, including monokaryotic strains carrying only MAT1-1 in their genomes and heterokaryotic strains harboring both MAT1-1 and MAT1-2. These strain groups are able to produce fruiting bodies under suitable cultivating conditions. In previous work, we showed that monokaryotic strains are more stable than heterokaryotic strains in fruiting body formation through successive culturing generations. In this study, we report a high cordycepin-producing monokaryotic C. militaris strain (HL8) collected in Vietnam. This strain could form normal fruiting bodies with high biological efficiency and contain a cordycepin content of 14.43mg/g lyophilized fruiting body biomass. The ethanol extraction of the HL8 fruiting bodies resulted in a crude extract with a cordycepin content of 69.15mg/g. Assays of cytotoxic activity on six human cancer cell lines showed that the extract inhibited the growth of all these cell lines with the IC50 values of 6.41-11.51µg/mL. Notably, the extract significantly reduced cell proliferation and promoted apoptosis of breast cancer cells. Furthermore, the extract also exhibited strong antifungal activity against Malassezia skin yeasts and the citrus postharvest pathogen Penicillium digitatum. Our work provides a promising monokaryotic C. militaris strain as a bioresource for medicine, cosmetics, and fruit preservation.

Novel biologically active paddlewheel-like palladium thiocyanate complex catalyzed cyanation of alkyl bromide utilizing Q-tube system: A green perspective

A novel paddlewheel-like complex of [Pd(SCN)2(3-Acpy)2], (1) was produced at ambient temperature by adding an aqueous solution of palladium chloride to an aqueous acetonitrile solution of 3-acetylpyridine (3-Acpy) and potassium thiocyanate. Elemental analysis, Fourier-transform infrared (FT-IR), ultraviolet–visible (UV–vis), and nuclear magnetic resonance (NMR) spectroscopic methods were used to characterize complex 1 comprehensively. Single crystal X-ray diffraction was used to analyze the crystal structure of complex 1. The palladium atom is bonded to two 3-Acpy ligands and two thiocyanates groups in trans mode giving square planer geometry in complex 1. The discrete units of paddlewheel-like complex 1 through hydrogen bonding extend to form a 3D supramolecular network structure. The synthesized and characterized new palladium complex 1 was utilized as a precatalyst for the cyanation of alkyl bromide using potassium ferrocyanide as a benign cyanide source reagent. The suggested catalytic test reaction under high-pressure conditions via a Q-tube system in green solvent cyclopentyl methyl ether introduced high yields and a short reaction time. Moreover, the cytotoxic activity of complex 1 was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against HePG-2 of liver cancer and MCF7 of breast cancer cell lines. According to the findings, complex 1 has significant strong activity against the cancer cell lines HePG-2 and MCF-7. Additionally, the luminescence spectra of complex 1 were investigated.

Lytic activity of phages against bacterial pathogens infecting diabetic foot ulcers

Complications of diabetes, such as diabetic foot ulcers (DFUs), are common, multifactorial in origin, and costly to treat. DFUs are the cause of nearly 90% of limb amputations among persons with diabetes. In most chronic infections such as DFU, biofilms are involved. Bacteria in biofilms are 100–1000 times more resistant to antibiotics than their planktonic counterparts. Multidrug-resistant (MDR) Staphylococcus aureus and Pseudomonas aeruginosa infections in DFUs may require alternative therapeutic agents such as bacteriophages ("phages"). This study describes the lytic activity of phage cocktails AB-SA01 (3-phage cocktail) and AB-PA01 (4-phage cocktail), which target S. aureus and P. aeruginosa, respectively. The host range and lytic effect of AB-SA01 and AB-PA01 on a planktonic culture, single-species biofilm, and mixed-species biofilm were evaluated. In vitro testing showed that 88.7% of S. aureus and 92.7% of P. aeruginosa isolates were susceptible to AB-SA01 and AB-PA01, respectively, in the planktonic state. The component phages of AB-SA01 and AB-PA01 infected 66% to 94.3% of the bacterial isolates tested. Furthermore, AB-SA01 and AB-PA01 treatment significantly (p < 0.05) reduced the biofilm biomass of their hosts, regardless of the antibiotic-resistant characteristics of the isolates and the presence of a non-susceptible host. In conclusion, the strong lytic activity, broad host range, and significant biofilm biomass reduction of AB-SA01 and AB-PA01 suggest the considerable potential of phages in treating antibiotic-resistant S. aureus and P. aeruginosa infections alone or as coinfections in DFUs.

Antioxidant Activity of Plant Extracts at Chattogram Hill Tracts, Chattogram, Bangladesh

In recent years, researchers have focused on natural antioxidants because they are good for human health. Most scientists believe that around two-thirds of the plants in the world have medicinal value and good antioxidant activity. The goal of this work was to estimate antioxidant activities of plant extracts, collected from Chattogram Hill Tracts, Chattogram. Different types of Plant leaves were extracted with different solvents like water, ethanol, methanol, and Pet ether. These extracts were then tested to see if they have any antioxidant properties using a method called DPPH radical scavenging. The present study found that all plant extracts exhibited remarkable antioxidant activity among them water extract of plants had the highest level of antioxidants followed by ethanol followed by methanol then Petroleum ether extracts. The high antioxidant activity of these might be due to the presence of hydroxyl groups containing substance in polar solvent extract and these hydroxyl groups can damage free radicals and possess the necessary resources for radical scavenging. This study confirms that many plant extracts have very strong antioxidant activity, which can help treat diseases caused by free radicals in the body.

Studies on the in vitro mechanism and in vivo therapeutic effect of the antimicrobial peptide ACP5 against Trichophyton mentagrophytes

Trichophyton mentagrophytes is a zoophilic dermatophyte that can cause dermatophytosis in humans and animals. Antimicrobial peptides (AMPs) are considered as a promising agent to overcome the drug-resistance of T. mentagrophytes. Our findings suggest that cationic antimicrobial peptide (ACP5) not only possesses stronger activity against T. mentagrophytes than fluconazole, but also shows lower toxicity to L929 mouse fibroblast cells than terbinafine. Notably, its resistance development rate after resistance induction was lower than terbinafine. The present study aimed to evaluate the fungicidal mechanism of ACP5 in vitro and its potential to treat dermatophyte infections in vivo. ACP5 at 1 ×MIC completely inhibited T. mentagrophytes spore germination in vitro. ACP5 severely disrupts the mycelial morphology, leading to mycelial rupture. Mechanistically, ACP5 induces excessive ROS production, damaging the integrity of the cell membrane and decreasing the mitochondrial membrane potential, causing irreversible damage in T. mentagrophytes. Furthermore, 1% ACP5 showed similar efficacy to the commercially available drug 1% terbinafine in a guinea pig dermatophytosis model, and the complete eradication of T. mentagrophytes from the skin by ACP5 was verified by tissue section observation. These results indicate that ACP5 is a promising candidate for the development of new agent to combat dermatophyte resistance.

Computational design and engineering of self-assembling multivalent microproteins with therapeutic potential against SARS-CoV-2

Multivalent drugs targeting homo-oligomeric viral surface proteins, such as the SARS-CoV-2 trimeric spike (S) protein, have the potential to elicit more potent and broad-spectrum therapeutic responses than monovalent drugs by synergistically engaging multiple binding sites on viral targets. However, rational design and engineering of nanoscale multivalent protein drugs are still lacking. Here, we developed a computational approach to engineer self-assembling trivalent microproteins that simultaneously bind to the three receptor binding domains (RBDs) of the S protein. This approach involves four steps: structure-guided linker design, molecular simulation evaluation of self-assembly, experimental validation of self-assembly state, and functional testing. Using this approach, we first designed trivalent constructs of the microprotein miniACE2 (MP) with different trimerization scaffolds and linkers, and found that one of the constructs (MP-5ff) showed high trimerization efficiency, good conformational homogeneity, and strong antiviral neutralizing activity. With its trimerization unit (5ff), we then engineered a trivalent nanobody (Tr67) that exhibited potent and broad neutralizing activity against the dominant Omicron variants, including XBB.1 and XBB.1.5. Cryo-EM complex structure confirmed that Tr67 stably binds to all three RBDs of the Omicron S protein in a synergistic form, locking them in the “3-RBD-up” conformation that could block human receptor (ACE2) binding and potentially facilitate immune clearance. Therefore, our approach provides an effective strategy for engineering potent protein drugs against SARS-CoV-2 and other deadly coronaviruses.Graphical

A Time Point Proteomic Analysis Reveals Protein Dynamics of Plasmodium Oocysts

The oocyst is a sporogonic stage of Plasmodium development that takes place in the mosquito midgut in about 2 weeks. The cyst is protected by a capsule of unknown composition, and little is known about oocyst biology. We carried out a proteomic analysis of oocyst samples isolated at early, mid, and late time points of development. Four biological replicates for each time point were analyzed, and almost 600 oocyst-specific candidates were identified. The analysis revealed that, in young oocysts, there is a strong activity of protein and DNA synthesis, whereas in mature oocysts, proteins involved in oocyst and sporozoite development, gliding motility, and invasion are mostly abundant. Among the proteins identified at early stages, 17 candidates are specific to young oocysts. Thirty-four candidates are common to oocyst and the merosome stages (sporozoite proteins excluded), sharing common features as replication and egress. Western blot and immunofluorescence analyses of selected candidates confirm the expression profile obtained by proteomic analysis.

Bacteria-targeted magnolol-loaded multifunctional nanocomplexes for antibacterial and anti-inflammatory treatment

Natural plant-derived small molecules have shown great potential for their antimicrobial and anti-inflammatory properties. In this study, we successfully developed a nanocomplex consisting of magnolol (Mag), a surfactant with an 18 carbon hydrocarbon chain and multi-amine head groups (C18N3), and a peptide (cyclic 9-amino acid peptide (CARG)) with targeting capabilities for Staphylococcus aureus (S. aureus). The obtained Mag/C18N3/CARG nanocomplexes exhibited strong antibacterial activity against S. aureus. Furthermore, they demonstrated anti-inflammatory effects by reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β from macrophage inflammatory cells. This was achieved through downregulating the activation of NF-κB, KEAP1, and NRF2 signaling pathways. In a murine skin infection model, the Mag/C18N3/CARG nanocomplexes effectively suppressed the growth of S. aureus in the infected area and promoted wound healing. Additionally, in a mouse model of acute kidney injury (AKI), the nanocomplexes significantly reduced the levels of blood urea nitrogen and creatinine, leading to a decrease in mortality rate. These findings demonstrate the potential of combining natural plant-derived small molecules with C18N3/CARG assemblies as a novel approach for the development of effective and safe antibacterial agents.

Biosynthetic ability of diverse basidiomycetous yeast strains to produce the natural antioxidant ergothioneine

Sixteen strains of basidiomycetous yeasts were evaluated for their capability to produce ergothioneine (EGT), an amino acid derivative with strong antioxidant activity. The cells were cultured in either two synthetic media or yeast mold (YM) medium for 72 h, after which cytosolic constituents were extracted from the cells with hot water. After analyzing the extracts via liquid chromatography-mass spectrometry (LC-MS), we found that all strains produced varying amounts of EGT. The EGT-producing strains, including Ustilago siamensis, Anthracocystis floculossa, Tridiomyces crassus, Ustilago shanxiensis, and Moesziomyces antarcticus, were subjected to flask cultivation in YM medium. U. siamensis CBS9960 produced the highest amount of EGT at 49.5 ± 7.0 mg/L after 120 h, followed by T. crassus at 30.9 ± 1.8 mg/L. U. siamensis was also cultured in a jar fermenter and produced slightly higher amounts of EGT than under flask cultivation. The effects of culture conditions, particularly the addition of precursor amino acids, on EGT production by the selected strains were also evaluated. U. siamensis showed a 1.5-fold increase in EGT production with the addition of histidine, while U. shanxiensis experienced a 1.8-fold increase in EGT production with the addition of methionine. These results suggest that basidiomycetous yeasts could serve an abundant source for natural EGT producers.

Sustainable Finished Leather Preservation

Part 1 of the current paper described the green synthesis of myrobalan capped copper nanoparticles for the preservation of the finished leather. In Part II of the current study, Copper Nanoparticles (CuNPs) were synthesized using green synthesis with wattle (tannin) extract as a reducing agent. Green synthesis is the preferred approach for the synthesis of metal nanoparticles due to its eco-friendly and cost-effectiveness for the preservation of finished leather. To improve the antibacterial qualities of leather with different types of finishes, the resin finished leather was coated with synthesized wattle copper nanoparticles (W-CuNPs). The chemical constituents of wattle induce the reduction of Cu2+ ions to CuNPs with the capping process and also remain as a stabilizing agent for the capping process. The formation of W-CuNPs was confirmed by UV-Spectroscopy at an absorbance of 467 nm. The identified functional groups such as -OH, C=C, and C-N were analyzed by Fourier transform infrared spectrum (FT-IR) which are responsible for the reduction and stabilization of copper nanoparticles. The spherical shape of the nanoparticles was ascertained by Scanning Electron Microscope (SEM), whereas Energy dispersive X-ray (EDX) studies confirmed the presence of copper with 65%. The average particle size of W-CuNPs was found to be 96 nm. The zeta potential value of -24 mv affirmed the stability of the W-CuNPs. The maximum zone of inhibition was 12 mm against Gram-positive (Bacillus subtilis) and 11 mm against Gram-negative (Serratia marcescens) bacteria on W-CuNPs coated finished leather, which exhibits strong antimicrobial activity. Hence, CuNPs synthesized by wattle extract have the potential to preserve the finished leather and its products as an antibacterial agent.

Strong Activity and No Resistance Induction Exerted by Cell-Free Supernatants from Lacticaseibacillus rhamnosus against Mono-Species and Dual-Species Biofilms of Wound Pathogens in In Vivo-like Conditions.

It is widely agreed that microbial biofilms play a major role in promoting infection and delaying healing of chronic wounds. In the era of microbial resistance, probiotic strains or their metabolic products are emerging as an innovative approach for the treatment of hard-to-heal (chronic) wounds due to their antimicrobial, healing, and host immune-modulatory effects. In this study, we aimed to investigate the potential of cell-free supernatants (CFS) from Lacticaseibacillus rhamnosus GG against mono- and dual-species biofilms of wound pathogens in a 3D in vitro infection model. Mature biofilms of Pseudomonas aeruginosa and Staphylococcus aureus were obtained on collagen scaffolds in the presence of a simulant wound fluid (SWF) and treated with CFS at different doses and time intervals. At 1:4 dilution in SWF, CFS caused a marked reduction in the colony forming-unit (CFU) numbers of bacteria embedded in mono-species biofilms as well as bacteria released by the biofilms in the supernatant. CFU count and electron microscopy imaging also demonstrated a marked antibiofilm effect against dual-species biofilms starting from 8 h of incubation. Furthermore, CFS exhibited acceptable levels of cytotoxicity at 24 h of incubation against HaCaT cells and, differently from ciprofloxacin, failed to induce resistance after 15 passages at sub-inhibitory concentrations. Overall, the results obtained point to L. rhamnosus GG postbiotics as a promising strategy for the treatment of wound biofilms.

Strain-specific features of Pleurotus ostreatus growth in vitro and some of its biological activities

BackgroundThe production of Pleurotus ostreatus mycelium as a promising object for use in food and other industries is hampered by a lack of information about the strain-specificity of this fungus mycelium growth and its acquisition of various biological activities. Therefore, this research aimed to investigate mycelial growth of different P. ostreatus strains on varies solid and liquid media as well as to evaluate strains antagonistic, antibacterial, antiradical scavenging activities, and total phenolic content.ResultsPotato Dextrose Agar medium was suitable for all strains except P. ostreatus strain 2460. The best growth rate of P. ostreatus 2462 strain on solid culture media was 15.0 ± 0.8 mm/day, and mycelia best growth on liquid culture media—36.5 ± 0.2 g/l. P. ostreatus strains 551 and 1685 were more susceptible to positive effect of plant growth regulators Ivin, Methyur and Kamethur. Using of nutrient media based on combination of natural waste (amaranth flour cake and wheat germ, wheat bran, broken vermicelli and crumbs) has been increased the yield of P. ostreatus strains mycelium by 2.2–2.9 times compared to the control. All used P. ostreatus strains displayed strong antagonistic activity in co-cultivation with Aspergillus niger, Candida albicans, Issatchenkia orientalis, Fusarium poae, Microdochium nivale in dual-culture assay. P. ostreatus 2462 EtOAc mycelial extract good inhibited growth of Escherichia coli (17.0 ± 0.9 mm) while P. ostreatus 2460 suppressed Staphylococcus aureus growth (21.5 ± 0.5 mm) by agar well diffusion method. The highest radical scavenging effect displayed both mycelial extracts (EtOH and EtOAc) of P. ostreatus 1685 (61 and 56%) by DPPH assay as well as high phenolic content (7.17 and 6.73 mg GAE/g) by the Folin-Ciocalteu’s method. The maximal total phenol content (7.52 mg GAE/g) demonstrated of P. ostreatus 2461 EtOH extract.ConclusionsIt is found that the growth, antibacterial, antiradical scavenging activity as well as total phenolic content were dependent on studied P. ostreatus strains in contrast to antagonistic activity. The proposed culture mediums of natural waste could be an alternative to commercial mediums for the production mycelial biomass of P. ostreatus strains.

Antimicrobial and anti-biofilm activity of a thiazolidinone derivative against Staphylococcus aureus in vitro and in vivo.

Staphylococcus aureus (S. aureus) causes many infections with significant morbidity and mortality. S. aureus can form biofilms, which can cause biofilm-associated diseases and increase resistance to many conventional antibiotics, resulting in chronic infection. It is critical to develop novel antibiotics against staphylococcal infections, particularly those that can kill cells embedded in biofilms. This study aimed to investigate the bacteriocidal and anti-biofilm activities of thiazolidinone derivative (TD-H2-A) against S. aureus. A total of 40 non-duplicate strains were collected, and the minimum inhibitory concentrations (MICs) of TD-H2-A were determined. The effect of TD-H2-A on established S. aureus mature biofilms was examined using a confocal laser scanning microscope (CLSM). The antibacterial effects of the compound on planktonic bacteria and bacteria in mature biofilms were investigated. Other characteristics, such as cytotoxicity and hemolytic activity, were researched. A mouse skin infection model was used, and a routine hematoxylin and eosin (H&E) staining was used for histological examination. The MIC values of TD-H2-A against the different S. aureus strains were 6.3-25.0 µg/mL. The 5 × MIC TD-H2-A killed almost all planktonic S. aureus USA300. The derivative was found to have strong bacteriocidal activity against cells in mature biofilms meanwhile having low cytotoxicity and hemolytic activity against Vero cells and human erythrocytes. TD-H2-A had a good bacteriocidal effect on S. aureus SA113-infected mice. In conclusion, TD-H2-A demonstrated good bacteriocidal and anti-biofilm activities against S. aureus, paving the way for the development of novel agents to combat biofilm infections and multidrug-resistant staphylococcal infections.IMPORTANCEStaphylococcus aureus, a notorious pathogen, can form a stubborn biofilm and develop drug resistance. It is crucial to develop new anti-infective therapies against biofilm-associated infections. The manuscript describes the new antibiotic to effectively combat multidrug-resistant and biofilm-associated diseases.

Green synthesis and anti-tumor activity of curcumin @ ZnO/CuO nanoparticles

Both zinc oxide and copper oxide nanoparticles are promising biologically active materials. Green synthesis approach was used to prepare mixed ZnO/CuO nanoparticles loaded with curcumin extract. The isolated mixed oxides loaded with curcumin (curcumin @ ZnO/CuO) was characterized by UV–visible spectra, FTIR spectra, X-ray powder diffractions (XRD),Transmittance electron microscope (TEM), Energy dispersive x-ray (EDX) and x-ray photoelectron spectroscopy (XPS) spectra. X-ray powder diffractions indicated that ZnO has wurtzite structure and CuO crystallizes in a monoclinic system. XPS confirmed the existence of both CuO and ZnO nanoparticles. TEM results indicated the formation of quantum dots of curcumin @ ZnO/CuO with size in the range 6–10 nm. The optical band gaps of curcumin @ ZnO/CuO were determined and found to be 3.4 and 4.05 eV, which are higher than the bulk. The effects of curcumin @ ZnO/CuO on hepatocellular (HEPG-2) and colorectal (HCT-116) carcinoma were estimated by cell viability, cell cycle and anti-apoptotic factors (caspase-3/7, topoisomerase 2beta and annexin). Strong cytotoxicity activity and apoptosis of tumor cells were observed for curcumin @ ZnO/CuO. The cytotoxicity of the current compounds showed higher activity in comparison with other compounds that were previously studied.

Purification, identification and molecular docking of dual-functional peptides derived from corn protein hydrolysates with antioxidant and antiadhesive activity against Helicobacter pylori.

More than 50% of the world's population is infected with Helicobacter pylori, which is classified as a group I carcinogen by the World Health Organization (WHO). Corn protein dual-functional peptides were identified and functionally analyzed in vitro and in silico. Two novel dual-functional peptides were identified as Cys-Gln-Asp-Val-Pro-Leu-Leu (CQDVPLL, CQ7) and Thr-Ile-Phe-Pro-Gln-Cys (TIFPQC, TI6) using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS). The antiadhesive effects against H. pylori of CQ7 and TI6 were 45.17 ± 2.41% and 48.62 ± 1.84% at 4 mg mL-1 , respectively. In silico prediction showed that CQ7 and TI6 had good physicochemical properties. Molecular docking demonstrated that CQ7 and TI6 could bind to the adhesins BabA and SabA by hydrophobic interactions and hydrogen bonds, preventing H. pylori infection. Moreover, CQ7 showed strong antioxidant activity due to its unique amino acid composition. The present study demonstrated that the identified peptides, CQ7 and TI6, possess antioxidant and antiadhesive effects, preventing H. pylori infection and alleviating oxidative injury to the gastric mucosa. © 2023 Society of Chemical Industry.

The intestinal delivery systems of ferulic acid: Absorption, metabolism, influencing factors, and potential applications

AbstractFerulic acid (FA) is a hydroxycinnamic acid known for its strong antioxidant activity and potential benefits for intestinal health. However, its poor water solubility and instability limit its effectiveness. To address these issues, different ways have been explored to protect FA against degradation and further exert its potential benefits. This review discusses the absorption and metabolism of FA in the gut, as well as its potential impact on intestinal health. It also compares different intestinal delivery systems, such as nanoparticles, electrospun nanofibers, microcapsules, cross‐linked polymer gels, and Pickering emulsions, which can improve the solubility, stability, and bioavailability of FA in the gastrointestinal tract. This comprehensive review provides valuable insights for using FA in food, pharmaceutical, and nutraceuticals products.

1,3-Disubstituted-1,2,4-triazin-6-ones with potent activity against androgen receptor-dependent prostate cancer cells

Synthesis and biological evaluation of a small, focused library of 1,3-disubstituted-1,2,4-triazin-6-ones for in vitro inhibitory activity against androgen-receptor-dependent (22Rv1) and androgen-receptor independent (PC3) castration-resistant prostate cancer (CRPC) cells led to highly active compounds with in vitro IC50 values against 22Rv1 cells of <200 nM, and with apparent selectivity for this cell type over PC3 cells. From metabolic/PK evaluations of these compounds, a 3–benzyl-1–(2,4-dichlorobenzyl) derivative had superior properties and showed considerably stronger activity, by nearly an order of magnitude, against AR–dependent LNCaP and C4–2B cells compared to AR–independent DU145 cells. This lead compound decreased AR expression in a dose and time dependent manner and displayed promising therapeutic effects in a 22Rv1 CRPC xenograft mouse model. Computational target prediction and subsequent docking studies suggested three potential known prostate cancer targets: p38a MAPK, TGF-β1, and HGFR/c–Met, with the latter case of c–Met appearing stronger, owing to close structural similarity of the lead compound to known pyridazin-3-one derivatives with potent c-Met inhibitory activity. RNA-seq analysis showed dramatic reduction of AR signalling pathway and/or target genes by the lead compound, subsequently confirmed by quantitative PCR analysis. The lead compound was highly inhibitory against HGF, the c–Met ligand, which fitted well with the computational target prediction and docking studies. These results suggest that this compound could be a promising starting point for the development of an effective therapy for the treatment of CRPC.