Search Results (447)

Background/Objectives: Gut microbiota research has gained momentum in recent years broadening knowledge of microbial components and their potential effects on health and well-being. Strong association between explicit microbes and metabolic diseases associated with obesity and type 2 diabetes mellitus, gastrointestinal disorders, neurodegenerative diseases, and even cancers have been established. Akkermansia muciniphila is a budding next-generation probiotic that plays an important role in systemic metabolism, intestinal health, and immune regulation, establishing strong implications for its use as a potent therapeutic intervention in diverse diseases. This project aimed at evaluating whether bacterial cell extracts of VH Akkermansia muciniphila (Vidya Strain; VS) can stimulate insulin secretion in INS-1 pancreatic beta cells and GLP-1 secretion in NCI-H716 human L-cells, both established in vitro models for studying metabolic regulation. Methods: Cultured VH Akkermansia muciniphila extracts were administered in a dose-dependent manner on INS-1 cells, and glucose-stimulated insulin secretion (GSIS) was measured via ELISA. Treated Human L-cell lines (NCI-H716) were analyzed for GLP-1 secretion. Results: Our study demonstrated that VH Akkermansia muciniphila extracts modestly increase insulin secretion from INS-1 beta cells and, more notably, induce a robust, dose-dependent rise in GLP-1 secretion from NCI-H716 L-cells, with the highest dose achieving over a 2000% increase comparable to glutamine. Conclusions: These findings suggest that VH A. muciniphila extracts may offer metabolic benefits by enhancing GLP-1 release, highlighting their potential for managing type 2 diabetes and obesity. Full article

Parietaria judaica L. (alfavaca-de-cobra) was investigated as a potential source of anticancer compounds. Leaf extracts obtained using solvents of different polarities were evaluated for their phytochemical profiles and cytotoxic activities against a panel of human cancer cell lines (glioblastoma LN-229, lung NCI-H1563, breast MDA-MB-231, liver HepG2, renal 769-P, cervical HeLa, and melanoma A-375) and a noncancerous HEK-293 cell line. LC-ESI-MS/MS analysis confirmed that the extracts are rich in polyphenols, including phenolic acids and flavonoids. Cytotoxicity was assessed via MTT and SRB assays, demonstrating dose-dependent antiproliferative effects. Among the extracts, the ethanolic fraction (PJ-E) exhibited the strongest cytotoxicity, with an IC₅₀ of 11.82 µg/mL against HeLa cells, while displaying a significantly higher IC₅₀ (139.42 µg/mL) against HEK-293, indicating tumor selectivity. The water extract (PJ-W) showed selective activity against lung cancer cells (IC₅₀ = 87.69 µg/mL), with minimal toxicity toward normal cells. The methanol/acetone extract (PJ-M) displayed intermediate activity, whereas the hexane extract (PJ-H) was the least effective. These findings highlight P. judaica, particularly its ethanolic extract, as a promising source of natural anticancer agents. Further research focusing on the isolation of active constituents, formulation development, and in vivo validation is warranted to support its therapeutic potential. Full article

Acute PM2.5 exposure has been implicated in lung cancer progression, yet its impact on genetically distinct NSCLC cells remains underexplored. This study investigates how mutation-specific transcriptional responses influence susceptibility to PM2.5-induced oncogenic alterations, focusing on A549 and NCI-H1975 cells. This provides preliminary insight into the transcriptomic effects of acute PM2.5 exposure in NSCLC cells with distinct oncogenic mutations (A549 and NCI-H1975), serving as a guide for understanding mutation-specific responses to environmental stress. Cells were exposed to PM2.5 (200 µg/mL, 24 h), followed by RNA sequencing and analysis. Gene ontology and pathway enrichment analyses were conducted to identify key molecular alterations associated with tumour progression. NCI-H1975 cells exhibited a stronger transcriptional response, with a higher fold change in differentially expressed genes (DEGs), indicating greater PM2.5 susceptibility. Upregulated genes were linked to oxidative stress, carcinogen activation, metabolic reprogramming, and therapy resistance, reinforcing tumour survival under PM2.5 stress. Conversely, the downregulation of tumour suppressor genes suggests immune suppression and potential immunotherapy resistance. This study reveals that acute PM2.5 exposure induces mutation-specific transcriptomic alterations in NSCLC, with EGFR-mutant cells exhibiting heightened oxidative stress, metabolic shifts, and immune evasion. The upregulation of key genes highlights the profound molecular impact of short-term exposure, paving the way for future studies on pollution-driven oncogenic mechanisms and resistance pathways. Full article

Linear DNA constructs are used in gene delivery and therapy application due to their capacity of integration into the mammalian genome, offering stable transgene expression. Compared to circular plasmids, linear DNA also has the advantage that its dimension and steric hindrance are directly correlated to the length of the nucleotide chain. These considerations make linear DNA an effective choice for gene delivery pilot studies, where formulations and transfection efficiency calculations are studied considering the nucleic acid dimensions. Meanwhile, the development of DNA–chitosan nanoparticles (NPs) has gained significant interest for their potential in nucleic acid delivery, especially as non-viral gene delivery systems and for embedding linear DNA fragments, as well as gene delivery to the lung. This study explored an easy polyelectrolyte complexing preparation of linear DNA-loaded chitosan nanoparticles. Among the different formulations of nanoparticles prepared, the optimal one exhibited a size of approximately 290 nm, an encapsulation efficiency of 86% and a zeta potential of 25 mV. Additionally, this study examined how the concentration of DNA in solution influenced nanoparticle formation, encapsulation efficiency and particle size. In particular, transient transfection of the chitosan–linear DNA fragment complex, encoding for green fluorescent protein (GFP), was conducted in human pulmonary distal lung cells (NCI-H441 cells), demonstrating successful cellular internalization and protein expression. These studies highlight the potential of DNA–chitosan NPs in nucleic acid delivery, particularly for pulmonary applications. Future works will focus on formulating the achieved carrier into an inhalable dosage form to improve its translational application. Full article

Background/Objectives: Camellia nitidissima Chi (C. nitidissima), a traditional Chinese “food and medicine homology” plant, has demonstrated potential anti-tumor properties. However, its mechanisms of anti-lung cancer activity via ferroptosis remain unclear. This study aimed to construct an integrated research system of “natural product extraction-purification, bioactivity evaluation, and computational drug screening” to explore the bioactive compounds in C. nitidissima leaves targeting HMOX-1-mediated ferroptosis and their anti-lung cancer mechanisms. Methods: Active fractions were prepared using ethanol extraction combined with polyamide column chromatography. The anti-lung cancer activity was evaluated using the NCI-H1975 cell model. Ferroptosis was verified via transmission electron microscopy (TEM), biochemical indicators, a PCR Array, and immunofluorescence. The bioactive compounds were identified using UPLC-Q Exactive MS, and their binding affinity to HMOX-1 was evaluated via molecular docking and dynamics simulations, followed by cellular validation. Results: The 95% F1 fraction from the extracts of C. nitidissima leaves exhibited the strongest anti-lung cancer activity, which could be significantly reversed by Ferrostatin-1. Furthermore, it induced typical ferroptosis-related structural damage in mitochondria, including shrinkage and a reduction in size, increased membrane density, and a reduction or even the disappearance of cristae structures. At the molecular level, this fraction significantly increased the levels of oxidative stress markers (ROS↑, MDA↑, Fe²⁺↑, and GSH↓) and upregulated the expression of key ferroptosis-related genes, including HMOX-1, CHAC1, and NOX1. Using UPLC-Q Exactive MS combined with computational simulation methods, four bioactive compounds with high affinity for HMOX1 were successfully identified, including isochlorogenic acid A (−8.4 kcal/mol), isochlorogenic acid C (−8.4 kcal/mol), apigenin (−7.8 kcal/mol), and chrysin (−7.3 kcal/mol). Cellular experiments validated that these compounds exhibited dose-dependent anti-proliferative effects. Conclusions: The leaves of C. nitidissima induce anti-lung cancer effects via HMOX-1-mediated ferroptosis. Isochlorogenic acid A/C, apigenin, and chrysin were identified as key bioactive components. These findings lay the foundation for the development of natural ferroptosis-targeted drugs. Full article

In the present study, we characterized and investigated the effect of the araçá-boi extract on antioxidant activity, cell viability, and the regulation of genes related to tumor suppression and epigenetic mechanisms in ovarian cancer cells. The results showed that araçá-boi extract revealed a remarkable diversity of phytochemicals (organic acids, phenolic acids, and flavonoids), significant antioxidant potential, and efficient scavenging of reactive oxygen species, particularly hydroxyl and peroxyl radicals. Gallic acid, one of the phenolic acids present in the extract, was used alone to verify its contribution to cytotoxic activities. Exposure of human ovarian cancer cells (NCI/ADR-RES and OVCAR3) to the extract (0.15–150 μg/mL) and gallic acid (6–48 μg/mL) resulted in a significant reduction in cell viability, particularly after 48 h of treatment. Both treatments modulated genes involved in DNA repair, tumor suppression, and epigenetic regulation. However, no changes were observed in the methylation status of the BRCA1 gene promoter region with either araçá-boi extract or gallic acid. These findings reinforce the therapeutic potential of araçá-boi extract and its phenolic compounds against ovarian cancer and point to the need for further studies to better elucidate the molecular pathways involved and validate these effects in vivo. Full article

Glucagon-like peptide-1 (GLP-1) is a hormone secreted from enteroendocrine cells that can promote weight loss and blood glucose improvement. We screened probiotic strains that effectively stimulate GLP-1 secretion from human enteroendocrine cells and then investigated the efficacy of this strain in a high-fat diet (HFD)-induced mouse model of obesity. Lactiplantibacillus plantarum GB104 greatly induced GLP-1 secretion by increasing expression of the proglucagon gene (GCG), but not the proprotein convertase subtilisin/kexin type 1 gene (PCSK1) in the human enteroendocrine cell line NCI-H716. In an HFD-induced mouse model of obesity, GB104 inhibited weight gain and improved blood glucose levels by increasing blood GLP-1 levels. It also tended to attenuate the HFD-induced changes in blood levels of other hormones and suppressed fat accumulation in the liver and adipose tissues. In white adipose tissue, GB104 suppressed inflammation by reducing pro-inflammatory M1 macrophages and increasing anti-inflammatory M2 macrophages and regulatory T cells. Probiotic strains that promote GLP-1 secretion, such as GB104, may serve as a promising candidate for dietary intervention against obesity and metabolic diseases. Full article

Immune checkpoint inhibitors like programmed cell death 1 (PD-1) antibodies have revolutionized cancer treatment, but patient response rates remain limited. Sialic acid-binding Ig-like lectin 15 (Siglec-15) has emerged as a promising new immune checkpoint target. Through phage display technology using a Bactrian camel immunized with recombinant human Siglec-15, we generated six anti-Siglec-15 camelid nanobodies and constructed chimeric heavy-chain antibodies by fusing the VHH domains with human IgG-Fc. Following expression in HEK293-F cells and purification, three antibodies (S1, S5, S6) demonstrated specific binding to both human and murine Siglec-15 in ELISA and biolayer interferometry assays. In a xenograft model established by subcutaneous inoculation of NCI-H157-S15 cells into BALB/c nude mice, these antibodies showed distinct tumor targeting and significant blockade of Siglec-15 interactions with CD44, MAG, sialyl-Tn, and LRR4C ligands. All three antibodies exhibited anti-tumor effects, with S1 showing the most potent activity. S1-treated mice had significantly smaller tumor volumes and weights compared to controls. The S1, S5, and S6 treatment groups showed enhanced anti-tumor immunity, with reduced TGF-β, IL-6, and IL-10 levels. Notably, S1 treatment significantly increased tumor-associated macrophages in tumor tissues (p < 0.05). In conclusion, S1 exhibits remarkable anti-tumor activity and has the potential to be developed as a cancer immunotherapy targeting Siglec-15. Full article

In this study, a novel 4-methylbenzoylhydrazide·dimethyl sulfoxide·dichloro platinum(II) complex (Pt2) was synthesized and characterized, and its anti-tumor activity and action mechanism were explored. The molecular structure and spatial configuration of the complex were determined using X-ray diffraction. The results obtained using fluorescence spectroscopy demonstrate that this complex can effectively bind to DNA and affect its fluorescence properties. The experimental results show that Pt2 exhibited significant inhibitory effects on a variety of tumor cell lines (MCF-7, HepG-2, NCI-H460, T24, and A549), and its IC50 values were lower than those of cisplatin (DDP), indicating stronger anti-tumor activity. In addition, the complex not only significantly induced the apoptosis of MCF-7 cells but also inhibited cell cycle arrest at the G₂ phase, with the proportion of G₂-phase cells as high as 49.47%. In conclusion, the 4-methylbenzoylhydrazide platinum(II) complex exhibits good anti-tumor activity by inducing apoptosis and inhibiting the cell cycle, providing an important experimental basis for the development of novel platinum-based anti-tumor drugs. Full article

The dinuclear platinum(IV) compound {Pt(CH₃)₃}₂(μ-I)₂(μ-adenine) (abbreviated Pt₂ad), obtained by treating cubic [Pt^IV(CH₃)₃(μ₃-I)]₄ with two equivalents of adenine, was isolated and structurally characterized by single crystal X-ray diffraction. The National Cancer Institute Developmental Therapeutics Program’s in vitro sulforhodamine B assays showed Pt₂ad to be particularly cytotoxic against the central nervous system cancer cell line SF-539, and the human renal carcinoma cell line RXF-393. Furthermore, Pt₂ad displayed some degree of cytotoxicity against non-small cell lung cancer (NCI-H522), colon cancer (HCC-2998, HCT-116, HT29, and SW-620), melanoma (LOX-IMVI, Malme-3M, M14, MDA-MB-435, SK-MEL-28, and UACC-62), ovarian cancer (OVCAR-5), renal carcinoma (A498), and triple negative breast cancer (BT-549, MDA-MB-231, and MDA-MB-468) cells. Although anticancer studies involving some adenine platinum(II) compounds have been reported, this study marks the first assessment of the anticancer activity of an adenine platinum(IV) complex. Full article

Tricyclic and tetracyclic lactone derivatives of thieno[2,3-b]pyrazine or thieno[2,3-b]quinoline, and 2H-pyrones were prepared using different methodologies. Pd/Cu-catalyzed Sonogashira coupling using Et₃N as a base, of methyl 7-bromothieno[2,3-b]pyrazine-6-carboxylate and (het)arylalkynes to yield the Sonogashira ester products, gave also the corresponding tricyclic lactones as minor products. However, the major products did not cyclize with TFA. Tricyclic lactones were then obtained by a tandem one-pot Sonogashira coupling and 6-endo-dig lactonization of 7-bromothieno[2,3-b]pyrazine-6-carboxylic acid with (het)arylalkynes, in good yields. Halogenated tricyclic lactones were synthesized by halocyclization using CuX and NXS. Tetracyclic lactones were synthesized through a Rh(III)-catalyzed formal [4+2] cycloaddition, between thieno[2,3-b]quinoline-2-carboxylic acid and internal alkynes, triggered by C-H activation, with the carboxylic group acting as a directing group. Using the SRB assay, the antitumor activity of both Sonogashira products and lactones was evaluated across five human cancer cell lines (CaCo-2, MCF-7, AGS, HeLa, NCI-H460). The best-performing compound was a Sonogashira product showing a GI₅₀ < 10 µM in all tumor cell lines and low toxicity in PLP2 cells. Additionally, antiparasitic testing against Trypanosoma brucei and Leishmania infantum revealed some compounds with IC₅₀ < 11 µM, though some level of cytotoxicity was observed in THP-1—derived macrophages. Full article

Background/Objectives: Antibody-based therapies often exhibit limited distribution within solid tumors due to the “binding-site barrier” (BSB). Our group has developed and validated the use of anti-idiotypic distribution enhancers (AIDEs), which transiently block antibody binding, improving intra-tumoral distribution and efficacy. This study evaluated 1HE and LG1, model anti-trastuzumab AIDEs, in combination with trastuzumab–PE24, a highly potent immunotoxin. Methods: The effects of 1HE on the whole-body disposition of radiolabeled trastuzumab were assessed in NCI-N87 tumor-bearing mice. Mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modeling was employed to explore how AIDE binding kinetics influence antibody intra-tumoral distribution and immunotoxin potency. Trastuzumab–PE24 was developed by site-specific conjugation, enabled by self-splicing split intein, with cytotoxicity tested on various cell lines in vitro. The impact of 1HE and LG1 coadministration on trastuzumab–PE24 efficacy was evaluated in NCI-N87 xenograft-bearing mice. Results: 1HE coadministration decreased trastuzumab tumor maximum concentration, reducing tumor terminal slope by 8% and overall tumor exposure by 2.6%, without negatively affecting selectivity. Modeling predicted the optimal AIDE dissociation rate constant for trastuzumab–PE24 to be between 0.015 and 0.3 h⁻¹. The coadministration of trastuzumab–PE24 with 1HE and LG1 improved anti-tumor efficacy and extended median survival to 60 days (p = 0.0002). Conclusions: AIDE coadministration led to minimal negative impacts on overall tumor exposure, consistent with model simulations. AIDE coadministration improved the efficacy of trastuzumab–PE24 in NCI-N87 xenografts. Modeling further predicted that repeated AIDE administration with trastuzumab–PE24 could induce complete tumor regression. These findings highlight the advantages of the AIDE strategy, particularly when coadministered with highly potent immunotoxins. Full article

Three new structures named naphpyrone I–K (1–3) that contain a 6/6/6/6 oxaphenalene pyranone skeleton were isolated and purified from a marine-derived Streptomyces sp. HDN155000. Their chemical structures, including configurations, were elucidated by extensive NMR, MS, single-crystal X-ray diffraction, theoretical NMR calculations, DP4+ probability analysis, and ECD analyses. Naphpyrone K (3) showed cytotoxic activities against L-02, K562, NCI-H446/EP, MDA-MB-231, and NCI-H446 cancer cells with IC₅₀ values of 5.13, 3.34, 2.50, 2.61, and 2.20 μM, respectively. These findings highlight the potential for screening and developing therapeutic drugs from aromatic polyketides derived from marine actinobacteria. Full article

With the global shift in energy structure and the advancement of the “double carbon” strategy, methanol has gained attention as a clean low-carbon fuel in the engine sector. However, the corrosion–wear coupling failure caused by acidic byproducts, such as methanoic acid and formaldehyde, generated during combustion severely limits the durability of methanol engines. In this study, we employed a systematic approach combining the construction of a corrosion liquid concentration gradient experiment with a full-load and full-speed bench test to elucidate the synergistic corrosion–wear mechanism of core friction pairs (cylinder liner, piston, and piston ring) in methanol-fueled engines. The experiment employed corrosion-resistant gray cast iron (CRGCI), high chromium cast iron (HCCI), and nodular cast iron (NCI) cylinder liners, along with F38MnVS steel and ZL109 aluminum alloy pistons. Piston rings with DLC, PVD, and CKS coatings were also tested. Corrosion kinetic analysis was conducted in a formaldehyde/methanoic acid gradient corrosion solution, with a concentration range of 0.5–2.5% for formaldehyde and 0.01–0.10% for methanoic acid, simulating the combustion products of methanol. The results showed that the corrosion depth of CRGCI was the lowest in low-concentration corrosion solutions, measuring 0.042 and 0.055 μm. The presence of microalloyed Cr/Sn/Cu within its pearlite matrix, along with the directional distribution of flake graphite, effectively inhibited the micro-cell effect. In high-concentration corrosion solutions (#3), HCCI reduced the corrosion depth by 60.7%, resulting in a measurement of 0.232 μm, attributed to the dynamic reconstruction of the Cr₂O₃-Fe₂O₃ composite passive film. Conversely, galvanic action between spherical graphite and the surrounding matrix caused significant corrosion in NCI, with a depth reaching 1.241 μm. The DLC piston coating obstructed the permeation pathway of formate ions due to its amorphous carbon structure. In corrosion solution #3, the recorded weight loss was 0.982 mg, which accounted for only 11.7% of the weight loss observed with the CKS piston coating. Following a 1500 h bench test, the combination of the HCCI cylinder liner and DLC-coated piston ring significantly reduced the wear depth. The average wear amounts at the top and bottom dead centers were 5.537 and 1.337 μm, respectively, representing a reduction of 67.7% compared with CRGCI, where the wear amounts were 17.152 and 4.244 μm. This research confirmed that the HCCI ferrite–Cr carbide matrix eliminated electrochemical heterogeneity, while the DLC piston coating inhibited abrasive wear. Together, these components reduced the wear amount at the top dead center on the push side by 80.1%. Furthermore, mismatches between the thermal expansion coefficients of the F38MnVS steel piston (12–14 × 10⁻⁶/°C) and gray cast iron (11 × 10⁻⁶/°C) resulted in a tolerance exceeding 0.105 mm in the cylinder fitting gap after 3500 h of testing. Notably, the combination of a HCCI matrix and DLC coating successfully maintained the gap within the required range of 50–95 μm. Full article

Three new complexes of copper(II) and chromone-2-carboxylic acid, a ligand from the group of hydroxypyrones, were synthesised according to the principles of green chemistry. The complexes were characterised by FT–IR and NMR spectroscopy, thermal and electrochemical analysis, and their structures are proposed. The results show the formation of mononuclear (1) and dinuclear hydroxo-bridged dinuclear copper(II) complexes (2 and 3). The results of cyclic voltammetry show that the copper in all complexes is in the +2-oxidation state. The antiproliferative activity was determined by MTT assay on 2D cell models in vitro on seven cell lines. The activity spectrum of complexes 1–3 ranged from the highest to the lowest value in the tumour cell lines tested, in the following order: Hep G2 > NCI-H358 > HT-29 > KATO III > MDA-MB 231 > Caco-2. The most effective concentration was 10⁻⁵ mol dm⁻³, which suppressed the growth of Hep G2 cells as follows: 69.5% (1), 64.8% (2) and 64% (3). The calculated selectivity index clearly shows that Hep G2 is the most sensitive cell line to copper complexes (SI = 1.623 (1); 1.557 (2), 1.431 (3). Full article