Lactobacillus Plantarum and its Derived Bacteriocin Exhibits Potent Antitumor Activity against Esophageal Cancer Cells.

Esophageal cancer presents a challenge in gastroenterology and traditional chemotherapy and radiation therapy have less therapeutic activity with severe side effects. Thus, there is need for effective and safer alternatives. Probiotics, particularly Lactobacillus plantarum (L. plantarum) and its bacteriocins, might prevent or treat esophageal tumors. We aimed to investigate the use of L. plantarum and its bacteriocin as esophageal cancer therapy. First, we obtained 100 isolates of Lactobacillus spp. from dairy product samples. They screened for bacteriocin production and identified by PCR and gel electrophoresis for 16S ribosomal RNA gene. Bacteriocin was partially purified and tested against two different pathogens. Both L. plantarum and its bacteriocin were examined for cytotoxicity in vitro against esophageal cancer cell line (SK-GT4) and normal rat embryo fibroblast (REF) cells by MTT assay. Apoptosis was determined using an acridine orange /propidium iodide assay. The results showed that the isolate gives a high bacteriocin production about (2000AU/ml). In addition to antimicrobial activity, there was significant anticancer activity. L. plantarum had an IC50 of 51.01 CFU/ml and bacteriocin IC50 of 281.9 AU/ml against cancer cells. Both showed no cytotoxicity towards normal REF cells. Furthermore, there was a significant increase in apoptosis induction and in caspase-3 activity in cancer cells treated with L. plantarum and bacteriocin compared to untreated cells. In conclusion, L. plantarum and its bacteriocin show potent killing effect against esophageal cancer cells with no effect against normal cells indicating safety and selectivity with activation of apoptosis via caspase-3 induction suggesting potential clinical advantage.

Preliminary Study on Pharmacokinetics and Antitumor Pharmacodynamics of Folic Acid Modified Crebanine Polyethyleneglycol-Polylactic Acid Hydroxyacetic Acid Copolymer Nanoparticles.

Purpose: Liver cancer is associated significantly with morbidity and mortality. The combination of low-intensity ultrasound with nanomedicine delivery systems holds promise as an alternative for the treatment for liver cancer. This study focuses on the utilization of folic acid (FA) modified nanoparticles, which are loaded with fluorescent dye DiR and liquid fluorocarbon (PFP). These nanoparticles have the potential to enhance liver cancer targeting under ultrasound stimulation and future applications in vivo. Methods: The pharmacokinetics and tissue distribution of folic acid-modified Crebanine polyethylene glycol-polylactic acid copolymer nanoparticles (FA-Cre@PEG-PLGA NPs) were investigated. The pharmacokinetic parameters, liver targeting, and in vivo distribution were assessed. Additionally, the inhibitory impacts of FA-Cre@PEG-PLGA NPs in combination with ultrasonic irradiation on the proliferation and acute toxicity of H22 cells of mouse hepatoma were investigated in vitro. The tumor targeting and anti-tumor efficacy of FA-Cre@PEG-PLGA NPs were assessed utilizing a small animal in vivo imaging system and an in situ hepatocellular carcinoma transplantation model, respectively. Results: The pharmacokinetic studies and tissue distribution tests demonstrated that FA-Cre@PEG-PLGA NPs conspicuously prolonged the half-life and retention time of the drug in rats, and the liver targeting effect was pronounced. Additionally, the in vivo acute toxicity test indicated that FA-Cre@PEG-PLGA NPs had minimal adverse reactions and could fulfill the aim of attenuating the drug. The outcomes of the animal experiments further substantiated that FA-Cre@PEG-PLGA NPs had a longer retention time at the tumor site, a superior anti-tumor effect, and less damage to liver and kidney tissue. Conclusion: The integration of FA-Cre@PEG-PLGA NPs with ultrasound irradiation demonstrated exceptional safety and potent anti-tumor efficacy in vivo, presenting a promising therapeutic strategy for the treatment of liver cancer through the combination of ultrasound technology with a nanomedicine delivery system.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) from Garcinia oblongifolia and their antitumoractivity.

Two new polycyclic polyprenylated acylphloroglucinols, along with four previously known compounds, were isolated and identified from the fruits of Garcinia oblongifolia. The structures of these compounds were elucidated through a combination of spectroscopic techniques, including MS, UV, IR, and 1D/2D NMR, as well as their chemical properties. Additionally, the cytotoxic activities of compounds 1‒6 against the H134B cell line were evaluated using the MTT assay, revealing that compounds 1 and 2 exhibit promising antitumor activity.

Targeted isolation of barrigenol-like triterpenoids from the husks of Xanthoceras sorbifolia Bunge based on feature-based molecular networking and their antitumor activities.

The husks of Xanthoceras sorbifolia Bunge have gradually attracted widespread attention in recent years due to the abundant resources and ideal pharmacological activities, with barrigenol-like triterpenoid saponins being its biological constituents. In this study, a feature-based molecular networking (FBMN) was utilized to perform the targeted isolation of triterpenoids. As a result, six undescribed barrigenol-type saponins (1-6) along with fourteen known analogues (7-22) were isolated from the extract of X. sorbifolia husk. Their structures were determined through a comprehensive analysis of NMR and HRMS spectroscopic data. Among them, compounds 1-3 are a specific type of saponin featuring a fucose moiety attached at C-21. The antitumor activities of isolated compounds were evaluated and compounds 7, 9 and 10 showed significant inhibitory activities against A549 and HepG2 cell lines in a dose-dependent manner.

Copper nanoparticles biosynthesis by Priestia megaterium and its application as antibacterial and antitumor agents.

The growth of material science and technology places high importance on creating better processes for synthesizing copper nanoparticles. Thus, an easy, ecological, and benign process for producing copper nanoparticles (CuNPs) has been developed using Priestia sp. bacteria utilizing a variety of low-cost agro-industrial wastes and byproducts. The biosynthesis of CuNPs was conducted using glucose medium and copper ions salt solution, then it was replaced by utilizing low-cost agro-industrial wastes. UV-visible spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), High-resolution transmission electron microscope (HR-TEM), Attenuated Total Reflectance and Fourier transform infrared (ATR-FTIR), and zeta potential were used to characterize the biosynthesized CuNPs. The cytotoxicity of CuNPs using Vero -CCL-81 cell lines, and antibacterial and antitumor properties using human colon epithelial colorectal adenocarcinoma Caco-2-HTB-37 cell lines were assessed. The UV-visible and DLS studies revealed CuNPs formation, with a maximum concentration of 6.19 ppm after 48 h, as indicated by a 0.58 Surface plasmon resonance (SPR) within 450 nm and 57.73 nm particle size. The 16S rRNA gene analysis revealed that Priestia sp. isolate is closely related to Priestia megaterium and has been deposited in the NCBI GenBank with accession number AMD 2024. The biosynthesis with various agro-industrial wastes indicated blackstrap sugar cane molasses being the most effective for reducing CuNPs size to 3.12 nm owing to various reducing and stabilizing active compounds. The CuNPs were free of contaminants, with a sphere-shaped structure and a cytotoxicity assessment with an IC50 of 367.27 µg/mL. The antibacterial activity exhibited by the most susceptible bacteria were Bacillus cereus ATCC 11788 and Staphylococcus aureus ATCC 6538 with inhibition zones of 26.0 mm and 28.0 mm, respectively. The antitumor effect showed an IC50 dose of 175.36 µg/mL. Based on the findings, the current work sought to lower product costs and provide a practical solution to the environmental contamination issues brought on by the buildup of agricultural wastes. In addition, the obtained CuNPs could be applied in many fields such as pharmaceuticals, water purification, and agricultural applications as future aspects.

A Polyurethane Electrospun Membrane Loaded with Bismuth Lipophilic Nanoparticles (BisBAL NPs): Proliferation, Bactericidal, and Antitumor Properties, and Effects on MRSA and Human Breast Cancer Cells.

Electrospun membranes (EMs) have a wide range of applications, including use as local delivery systems. In this study, we manufactured a polyurethane Tecoflex™ EM loaded with bismuth-based lipophilic nanoparticles (Tecoflex™ EMs-BisBAL NPs). The physicochemical and mechanical characteristics, along with the antitumor and bactericidal effects, were evaluated using a breast cancer cell line and methicillin-susceptible and resistant Staphylococcus aureus (MRSA). Drug-free Tecoflex™ EMs and Tecoflex™ EMs-BisBAL NPs had similar fiber diameters of 4.65 ± 1.42 µm and 3.95 ± 1.32 µm, respectively. Drug-free Tecoflex™ EMs did not negatively impact a human fibroblast culture, indicating that the vehicle is biocompatible. Tecoflex™ EMs-BisBAL NPs increased 94% more in size than drug-free Tecoflex™ EMs, indicating that the BisBAL NPs enhanced hydration capacity. Tecoflex™ EMs-BisBAL NPs were highly bactericidal against both methicillin-susceptible S. aureus and MRSA clinical isolates, inhibiting their growth by 93.11% and 61.70%, respectively. Additionally, Tecoflex™ EMs-BisBAL NPs decreased the viability of MCF-7 tumor cells by 86% after 24 h exposure and 70.1% within 15 min. Regarding the mechanism of action of Tecoflex™ EMs-BisBAL NPs, it appears to disrupt the tumor cell membrane. In conclusion, Tecoflex™ EMs-BisBAL NPs constitute an innovative low-cost drug delivery system for human breast cancer and postoperative wound infections.

Alginate sulfonamide hydrogel beads for 5-fluorouracil delivery: antitumor activity, cytotoxicity assessment, and theoretical investigation.

This study focused on grafting a new monomer (E)-N-(4-(3-(4-bromophenyl) acryloyl) phenyl)-4-methyl benzene sulfonamide (Br-PS) onto sodium alginate (Alg) using a free radical polymerization method. The optimal parameters for the grafting polymerization reaction were investigated, including initiator and monomer concentrations, polymerization reaction duration, and temperature. Additionally, the conversion, graft, and solid content percentages were calculated. The resulting novel poly (Br-PS)-g-Alg was thoroughly analyzed using Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM). Moreover, poly (Br-PS)-g-Alg was tested for cytotoxicity and selectivity values on lung cancer cell line (A549), breast cancer cell line (MDA-MB-231), and a normal cell line (MDCK) using the neutral red uptake test. Poly (Br-PS)-g-Alg demonstrated more inhibitory impact (IC50 = 33.37 and 40.9 µg/mL) and high selectivity (selectivity index = 4.83 and 3.94) on the A549 and MDA-MB-231 cell lines, respectively. Furthermore, uniform beads of creative poly (Br-PS)-g-Alg were fabricated, and their swelling rate in various media was studied. These beads could potentially serve as drug carriers for 5-fluorouracil (5-FU). Release experiments in simulated gastric (SGF) and intestinal fluids (SIF) showed a slower 5-FU release pattern in SGF compared to SIF. The proposed structures of poly (Br-PS)-g-Alg were theoretically verified using density functional theory with DFT/B3LYP/6-31(G) basis set, revealing distinct interactions due to the presence of different functional groups. The findings of this study could significantly impact the development of new drug delivery systems.

Mitochondrion-targeted selenium nanoparticles stabilized by Sargassum fusiforme polysaccharides increase reactive oxygen species-mediated antitumour activity.

Authors prepared a nanoselenium particle stabilized with Sargassum fusiforme polysaccharide (SFPS-Tw-SeNPs) and confirmed that it could effectively inhibit the proliferation of A549 lung cancer cells in vitro. The aim of this study was to investigate its anti-lung cancer effect in vitro and in vivo and its possible mechanism. In cell experiments, AO/EB staining revealed that SFPS-Tw-SeNPs could induce the apoptosis of A549 cells and produce red fluorescence by inserting into DNA through damaged cell membranes, increasing the production of reactive oxygen species (ROS). SFPS-Tw-SeNPs that is loaded with coumarin-6 entered the cells in a concentration-dependent and time-dependent manner, acting on the mitochondria, reducing the mitochondrial membrane potential, increasing the Bax/Bcl-2 ratio, and increasing the expression of Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP and Cytochrome C-induced apoptosis in cells. In addition, the SFPS-Tw-SeNPs blocked the PI3K/AKT signalling pathway, downregulated the expression of Cyclin-A and CDK2, upregulated the expression of P21, and arrested the cell in the G1 phase. In animal experiments, SFPS-Tw-SeNPs treatment significantly inhibited the growth of A549 tumour xenografts but did not significantly negatively affect the body of the animals. Overall, SFPS-Tw-SeNPs have the potential to be developed as a pharmaceutical drug to prevent and treat non-small cell lung cancer.

Synthesis and evaluation of anticancer activity of new 4,5,6,7-tetrabromo-1H-benzimidazole derivatives.

An efficient method for the synthesis of new 4,5,6,7-tetrabromo-1H-benzimidazole derivatives has been developed. New ketones were obtained by N-alkylation of TBBi or 2-Me-TBBi with various phenacyl halides and then reduced to the corresponding alcohols. All compounds were obtained with satisfactory yields in the range of 40-91 %. The synthesized compounds appeared a weak CK2 and PIM-1 inhibitors but exhibit an interesting cytotoxic activity against cancer cell lines, i.e. MCF-7, PC-3, CCRF-CEM, K-562. 1-Phenyl-2-(4,5,6,7-tetrabromo-1H-benzimidazol-1-yl)ethanone 3aA exhibits the highest cytotoxic activity with IC50 value of 5.30 µM for MCF-7 and 6.80 µM for CCRF-CEM. Moreover, this compound shows the highest selectivity against both MCF-7 and CCRF-CEM with SI selectivity coefficients (against MRC-5 and Vero cells) equal 5.45 and 4.30 for MCF-7 and 4.25 and 3.35 for CCRF-CEM, respectively. Furthermore, it was shown that compound 3aA exhibits very good pro-apoptotic properties, through induction of the mitochondrial apoptotic pathway in CCRF-CEM cells. These results correlate with data showing the effect of 3aA on intracellular level of CK2α protein and CK2-mediated phosphorylation of Ser529 in NF-κBp65. Study of the effect of compound 3aA on mRNA levels of CK2α and CK2α' showed no significant differences in gene expression levels in control CCRF-CEM and cells treated with 3aA, indicating 3aA action at the protein level.

Synthesis and Antitumour Activity of Hybrid Compounds Based on 4-Aminophenylarsonic Acid and Spatially Hindered Phenols.

One of the main modern approaches to the creation of effective drugs is the design of new biologically active substances containing two or more pharmacophore groups in their structure. In recent years, there have been many publications on the synthesis and study of biological activity, including antitumour activity, of new organo-arsenic compounds. It is known that spatially hindered phenols can also have antitumor activity, so the synthesis and study of hybrid compounds based on organo-arsenic compounds and spatially hindered phenols is a relevant area of research. In this work, the modification of 4-aminophenylarsonic acid with 3,5-di-tert-butyl-4-hydroxybenzylacetate was carried out. In contrast to a similar transformation of 2-aminophenylarsonic acid, in this case it was possible to obtain both mono- and di-benzyl derivatives of the acid. Using the Zandmeyer method, the oxime isatin containing an arsonic acid fragment in the fifth position of the heterocycle was synthesised. Azo derivatives containing fragments of para-aminophenylarsonic acid and sterically hindered phenols were obtained. 4-((3,5-Di-tert-butyl-2-hydroxyphenyl)diazenyl)phenylarsonic acid was isolated in pure form. At the same time, it was found that the reaction of the diazonium azo salt of 4-aminophenylarsonic acid with 2-hydroxymethyl-4-tert-butylphenol proceeds in two directions. In addition to the classical diazotisation reaction at the 6-position of 2-hydroxymethyl-4-tert-butylphenol, a diazotisation accompanied by a dehydroxymethylation process occurs. The obtained compounds showed cytotoxic activity against human tumor cell lines M-HeLa (cervical epithelioid carcinoma) and HuTu 80 (duodenal adenocarcinoma cells). The most promising is the sodium salt of 4-((3,5-di-tert-butyl-2-hydroxyphenyl)diazenyl)phenylarsonic acid, which is superior to Tamoxifen and 5-fluorouracil in terms of selectivity index towards M-HeLa and HuTu 80 cells.

Novel tris-bipyridine based Ru(II) complexes as type-I/-II photosensitizers for antitumor photodynamic therapy through ferroptosis and immunogenic cell death.

Ru(II) complexes have attracted attention as photosensitizers for their promising photodynamic properties. Herein, novel tris-bipyridine based Ru(II) complexes (6a-e) were synthesized by introducing saturated heterocycles to improve photodynamic properties and lipid-water partition coefficients. Among them, 6d demonstrated significant phototoxicity towards three cancer cells, with IC50 values of 5.66-7.17 µM, exceeding values in dark (IC50s > 100 µM). Under hypoxic conditions, 6d maintained excellent photodynamic activity in A549 cells, with PI values exceeding 24, highlighting its potential for highly effective type-I/-II photodynamic therapy by inducing ROS generation, oxidative stress, and mitochondrial damage. Additionally, it induced ferroptosis and immunogenic cell death of A549 cells by regulating the expression of relevant markers. Finally, 6d remarkably inhibited the growth of A549 transplanted tumor growth by 95.4 %. This Ru(II) complex shows great potential for cancer treatment with its potent photodynamic activity and diverse mechanisms of tumor cell death.

Sm(â ¢), Gd(â ¢), and Eu(â ¢) complexes with 8-hydroxyquinoline derivatives as potential anticancer agents via inhibiting cell proliferation, blocking cell cycle, and inducing apoptosis in NCI-H460 cells.

Four lanthanide complexes with 8-hydroxyquinoline-2-aldehyde-2-hydrazinopyridine (H-L1), 8-hydroxyquinoline-2-aldehyde-2-hydrazimidazole (H-L2): [Sm(L1)2][Sm(L1)(NO3)3]·CHCl3·2CH3OH (1), [Gd(L1)2][Gd(L1)(NO3)3]·CHCl3·2CH3OH (2), [Sm(L2)(NO3)2]2·CH3OH (3), and [Eu(L2)(NO3)2]2·CH3OH (4) were synthesized and characterized. In vitro cytotoxicity evaluation showed that the ligands and four lanthanide complexes exhibited cytotoxicity to the five tested tumor cell lines. Among them, complex 1 showed the best antiproliferative activity against NCI-H460 tumor cells. Mechanistic studies demonstrated that complex 1 arrested the cell cycle of NCI-H460 cells in G1 phase and induced mitochondria-mediated apoptosis, which resulted in the loss of mitochondrial membrane potential, enhanced intracellular Ca2+ levels and reactive oxygen species generation. In addition, complex 1 affected the expression levels of intracellular apoptosis-related proteins and activated the caspase-3/9 in NCI-H460 cells. Therefore, complex 1 is a potential anticancer agent.

[Cytotoxicity Studies of 5-Arylaminouracil Derivatives].

We have previously shown that 5-arylaminouracil derivatives can inhibit HIV-1, herpesviruses, mycobacteria, and other pathogens through various mechanisms. The purpose of this study was to evaluate the potential of 5-arylaminouracils and their derivatives against leukemia, neuroblastoma, and glial brain tumors. 5-Aminouracils with various substituents and their 5'-norcabocyclic and ribo derivatives were screened for cytotoxicity against two neuroblastoma cell lines (SH-SY5Y and IMR-32), K-562 lymphoblastic cells, HL-60 promyeoloblastic cells, and low-passage variants of well-differentiated glioblastoma multiforme (GBM5522 and GBM6138). Cytotoxicity assessment by the standard MTT test showed that most of the compounds lack significant toxicity towards the above cells. However, 5-(4-isopropylphenylamine)uracil and 5-(4-tert-butylphenylamine)uracil exhibited a dose-dependent toxic effect towards the GBM6138 cell line with half-maximal inhibitory concentrations (IC50) of 9 and 2.3 µÐœ, respectively. Antitumor activity was for the first time demonstrated for compounds of this type and can serve as a starting point for further research.

Two new compounds from the capitula of Chrysanthemum morifolium cv. Fubaiju.

A new germacrane-type sesquiterpenoid (1) and a new alkamide (2), as well as six known compounds (3-8) were isolated from the capitula of Chrysanthemum morifolium cv. Fubaiju. The new structures were elucidated by comprehensive spectroscopic analysis and quantum chemical calculations. The known structures were characterised via 1D NMR data compared with the already existing literature data. Among the isolates, compound 5 showed inhibitory activity against human lung cancer A549 cells and human hepatoma HepG2 cells with the IC50 values of 19.50 ± 1.23 and 23.24 ± 1.30 µM, respectively, and compound 8 exhibited inhibitory effect on RSV infection with IC50 value of 12.50 ± 1.02 µM.

A biodegradable Fe-0.6Se alloy with superior strength and effective antibacterial and antitumor capabilities for orthopedic applications.

Iron-selenium (Fe-Se) alloys have potential as attractive biodegradable bone-implant materials, given the antitumor properties of Se in cancer prevention and therapy. However, the fabrication of Fe-Se alloys is challenging due to the volatility of elemental Se and the significantly different melting points of Se and Fe. In this study, we successfully fabricated Fe-xSe (x = 0.2, 0.4, 0.6, 0.8, and 1 wt.%) alloys using suction casting, with FeSe compounds as the Se source. The microstructures, tensile properties, corrosion behavior, biocompatibility, antibacterial ability, and antitumor properties of the Fe-Se alloys were evaluated. The microstructures of the Fe-Se alloys were composed of α-Fe and FeSe phases. Among the Fe-Se alloys, Fe-0.6Se showed the best combination of tensile properties, with a yield strength of 1096.5 ± 7.2 MPa, an ultimate tensile strength of 1271.6 ± 6.3 MPa, and a fracture strain of 15.6 ± 3.3 %, and a degradation rate of 56.9 ± 0.4 µm/year. Moreover, the Fe-0.6Se alloy showed superb antibacterial ability against S. aureus, antitumor activity against 143B osteosarcoma cells, and osteogenicity and biocompatibility toward pre-osteoblast MC3T3-E1 cells. In summary, adding 0.2-1.0 wt.% Se to Fe does not affect the growth of healthy cells but effectively inhibits the growth and reproduction of tumor cells, and the Fe-0.6Se alloy is promising for orthopedic applications owing to its unique combination of mechanical and biofunctional properties. STATEMENT OF SIGNIFICANCE: This work reports on Fe-xSe (x = 0.2, 0.4, 0.6, 0.8, and 1 wt.%) alloys fabricated using suction casting. The microstructures of the Fe-Se alloys were composed of α-Fe and FeSe phases. Among the Fe-Se alloys, the Fe-0.6Se showed the best combination of tensile properties, with a yield strength of 1058.6 ± 3.9 MPa, an ultimate tensile strength of 1134.1 ± 2.9 MPa, and a fracture strain of 16.8 ± 1.5 %, and a degradation rate of 56.9 ± 0.4 µm/year. Moreover, the Fe-0.6Se alloy showed superb antibacterial ability against S. aureus, antitumor activity against 143B osteosarcoma cells, and significant osteogenic ability and biocompatibility toward pre-osteoblast MC3T3-E1 cells. In summary, the Fe-0.6Se alloy is promising for orthopedic applications owing to its unique combination of mechanical and biofunctional properties.

pH-responsive magnetic CuFe2O4-PMAA nanogel conjugated with amino-modified lignin for controlled breast cancer drug delivery.

In this study, a novel magnetic and pH-responsive nanocarrier was developed, incorporating both natural and synthetic polymers, for delivering curcumin (CUR) to breast cancer cells. For this purpose, CuFe2O4@poly(methacrylic acid) (CuFe2O4@PMAA) nanogel was developed and conjugated with amino-modified lignin (Lignin-adipic acid dihydrazide conjugate, Lig-ADH) to achieve the CuFe2O4@PMAA@Lig-ADH nanocarrier. The morphology, structure, and physical properties of the synthesized nanomaterials were examined using a range of techniques, including transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), energy dispersive X-ray (EDX), and vibrating sample magnetometer (VSM). The synthesized nanocarrier exhibited a spherical shape, with an average diameter of approximately 15 nm, and demonstrated good magnetic responsiveness. Moreover, the in vitro drug release was found to be pH-dependent, with an increased release rate in acidic conditions. To evaluate cytotoxicity, the survival of MCF-7 cells was measured using the MTT assay for 24 h. Notably, the synthesized CuFe2O4@PMAA@Lig-ADH@CUR and CUR exhibited significant cytotoxic effects, effectively eliminating MCF-7 cells with IC50 values of 39.80 µg/mL and 4.27 µg/mL, respectively. Also, the significant intracellular uptake of NPs was confirmed by FITC and DAPI staining after 4 h. This research highlighted the potential of CuFe2O4@PMAA@Lig-ADH@CUR as a highly effective nano-delivery system and demonstrated a straightforward method for utilizing renewable lignin.

A monoclonal antibody recognizing CD98 on human embryonic stem cells shows anti-tumor activity in hepatocellular carcinoma xenografts.

CD98, also known as SLC3A2, is a multifunctional cell surface molecule consisting of amino acid transporters. CD98 is ubiquitously expressed in many types of tissues, but expressed at higher levels in cancerous tissues than in normal tissues. CD98 is also upregulated in most hepatocellular carcinoma (HCC) patients; however, the function of CD98 in HCC cells has been little studied. In this study, we generated a panel of monoclonal antibodies (MAbs) against surface proteins on human embryonic stem cells (hESCs). NPB15, one of the MAbs, bound to hESCs and various cancer cells, including HCC cells and non-small cell lung carcinoma (NSCLC) cells, but not to peripheral blood mononuclear cells (PBMCs) and primary hepatocytes. Immunoprecipitation and mass spectrometry identified the target antigen of NPB15 as CD98. CD98 depletion decreased cell proliferation, clonogenic survival, and migration and induced apoptosis in HCC cells. In addition, CD98 depletion decreased the expression of cancer stem cell (CSC) markers in HCC cells. In tumorsphere cultures, the expression of CD98 interacting with NPB15 was significantly increased, as were known CSC markers. After cell sorting by NPB15, cells with high expression of CD98 (CD98-high) showed higher clonogenic survival than cells with low expression of CD98 (CD98-low) in HCC cells, suggesting CD98 as a potential CSC marker on HCC cells. The chimeric version of NPB15 was able to induce antibody-dependent cellular cytotoxicity (ADCC) against HCC cells in vitro. NPB15 injection showed antitumor activity in an HCC xenograft mouse model. The results suggest that NPB15 may be developed as a therapeutic antibody for HCC patients.

Ultrasonic-assisted synthesis and antitumor evaluation of novel variant heterocyclic compounds based on piperidine ring.

Aim: This work explores the eco-friendly synthesis of various heterocycles from a piperidine-based compound (1) and explore their potential as antitumor agents.Materials & methods: Ultrasonic irradiation was used to synthesize heterocycles like pyridone, thiophene and coumarin, with computational tools analyzing stability and biological interactions.Results: Compounds 9 and 14 exhibit strong cytotoxic activity, surpassing doxorubicin. Compounds 2, 6, 10 and 13 exhibited intermediate activity, while compounds 3, 7 and 12 had minimal effects. Docking studies suggest potential ADORA1 receptor interaction. Computational tools analyze stability and interaction with biological systems, revealing potential antitumor mechanisms.Conclusion: Green synthesis of diverse heterocycles yielded potent antitumor agents (compounds 9 & 14). DFT and Docking studies suggest interaction with ADORA1 receptor, a potential mechanism.

[Box: see text].

Novel 3-substituted coumarins inspire a custom pharmacology prediction pipeline: an anticancer discovery adventure.

Aim: This research aims to expand the established pharmacological space of tumor-associated carbonic anhydrases (TACAs) by exploring the synthetically accessible chemical space of 3-substituted coumarins, with the help of in silico pharmacology prediction.Materials & methods: 52 novel 3-substituted coumarins were sketched, prioritizing synthetic feasibility. Their pharmacological potentials were estimated using a custom machine-learning approach. 17 compounds were predicted as cytotoxic against HeLa cells by interfering with TACAs. Those compounds were synthesized and biologically tested against HeLa cells. The three most potent compounds were assayed against multiple carbonic anhydrases, and their enzyme binding mechanism(s) were studied using molecular docking.Results: Experimental results exhibited pronounced consensus with in silico pharmacology predictions.Conclusion: Novel 3-substituted coumarins are herein dispatched to the cancer therapeutics space.

[Box: see text].

Evaluation of prognostic efficacy of liver immune status index in predicting postoperative outcomes in hepatocellular carcinoma patients: A multi-institutional retrospective study.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks third in cancer-related deaths globally. Despite treatment advances, high post-hepatectomy recurrence rates (RR), especially with liver fibrosis and hepatitis C virus infection, remain challenging. Key prognostic factors include vascular invasion and perioperative blood loss, impacting extrahepatic recurrence. Natural killer (NK) cells are crucial in countering circulating tumor cells through TRAIL-mediated pathways. The aim of this study was to validate the liver immune status index (LISI) as a predictive tool for liver NK cell antitumor efficiency, particularly in HCC patients with vascular invasion. METHODS: A retrospective analysis of 1337 primary HCC hepatectomies was conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Clinicodemographic data were extracted from electronic medical records. Prognostic indices (FIB-4, ALBI, ALICE, GNRI, APRI, and LISI) were evaluated using area under the receiver operating characteristic curve values. Survival analyses employed Kaplan-Meier estimations and log-rank tests. RESULTS: LISI significantly correlated with other prognostic markers and stratified patients into risk groups with distinct overall survival (OS) and RR. It showed superior predictive performance for 2-year OS and RR, especially in patients with vascular invasion. Over longer periods, APRI and FIB-4 index reliabilities improved. The HISCO-HCC score, combining LISI, tumor burden score, and alpha-fetoprotein levels, enhanced prognostic accuracy. CONCLUSION: LISI outperformed existing models, particularly in HCC with vascular invasion. The HISCO-HCC score offers improved prognostic precision, guiding immunotherapeutic strategies and individualized patient care in HCC.