Photothermal and ferroptosis synergistic therapy for liver cancer using iron-doped polydopamine nanozymes.

An innovative nanozyme, iron-doped polydopamine (Fe-PDA), which integrates iron ions into a PDA matrix, conferred peroxidase-mimetic activity and achieved a substantial photothermal conversion efficiency of 43.5 %. Fe-PDA mediated the catalysis of H2O2 to produce toxic hydroxyl radicals (•OH), thereby facilitating lipid peroxidation in tumour cells and inducing ferroptosis. Downregulation of solute carrier family 7 no. 11 (SLC7A11) and solute carrier family 3 no. 2 (SLC3A2) in System Xc- resulted in decreased intracellular glutathione (GSH) production and inactivation of the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) pathway, contributing to ferroptosis. Moreover, the application of photothermal therapy (PTT) enhanced the effectiveness of chemodynamic therapy (CDT), accelerating the Fenton reaction for targeted tumour eradication while sparing adjacent non-cancerous tissues. In vivo experiments revealed that Fe-PDA significantly hampered tumour progression in mice, emphasizing the potential of the dual-modality treatment combining CDT and PTT for future clinical oncology applications.

Multifunctional Sr/Se co-doped ZIF-8 nanozyme for chemo/chemodynamic synergistic tumor therapy via apoptosis and ferroptosis.

Rationale: Cancer continues to be a significant public health issue. Traditional treatments such as surgery, radiotherapy, and chemotherapy often fall short because of intrinsic issues such as lack of specificity and poor drug delivery, leading to insufficient drug concentration at the tumor site and/or potential side effects. Consequently, improving the delivery of conventional chemotherapy drugs like doxorubicin (DOX) is crucial for their therapeutic efficacy. Successful cancer treatment is achieved when regulated cell death (RCD) of cancer cells, which includes apoptotic and non-apoptotic processes such as ferroptosis, is fundamental to successful cancer treatment. The developing field of nanozymes holds considerable promise for innovative cancer treatment approaches. Methods: A dual-metallic nanozyme system encapsulated with DOX was created, derived from metal-organic frameworks (MOFs), designed to combat tumors by depleting glutathione (GSH) and concurrently liberating DOX. The initial phase of the study examined the GSH oxidase-mimicking function of the dimetallic nanozyme (ZIF-8/SrSe) through enzyme kinetic assays and Density Functional Theory (DFT) simulations. Following this, we probed the ability of ZIF-8/SrSe@DOX to release DOX in response to the tumor microenvironment in vitro, alongside examining its anticancer capabilities and mechanisms prompting apoptosis or ferroptosis in cancer cells. Moreover, we established tumor-bearing animal models to corroborate the anti-tumor effectiveness of our nanozyme complex and to identify the involved apoptotic and ferroptotic pathways implicated. Results: Enzyme kinetic analyses demonstrated that the ZIF-8/SrSe nanozyme exhibits substantial GSH oxidase-like activity, effectively oxidizing reduced GSH to glutathione disulfide (GSSG), while also inhibiting glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). This inhibition led to an imbalance in iron homeostasis, pronounced caspase activation, and subsequent induction of apoptosis and ferroptosis in tumor cells. Additionally, the ZIF-8/SrSe@DOX nanoparticles efficiently delivered DOX, causing DNA damage and further promoting apoptotic and ferroptotic pathways. Conclusions: This research outlines the design of a novel platform that combines chemotherapeutic agents with a Fenton reaction catalyst, offering a promising strategy for cancer therapy that leverages the synergistic effects of apoptosis and ferroptosis.

Mo3Se4 nanoparticle with ROS scavenging and multi-enzyme activity for the treatment of DSS-induced colitis in mice.

Ulcerative colitis (UC), as a most common inflammatory bowel disease (IBD), has become a global public health concern. Exploring novel method of treating UC is urgent and necessary. Recently, nanozyme with excellent antioxidant properties may be one useful therapeutic strategy. In this study, a two-dimensional transition metal chalcogenide (TMCs) nano flake and polyethylene glycol (PEG) modified Mo3Se4 nano flakes (PMNFs) was synthesized, which had multi-enzyme activity, including peroxidase, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). The inhibition effect of PMNFs on sodium dextran sulfate (DSS)-induced colitis was explored. UC was effectively inhibited by PMNFs in this work. PMNFs significantly reduced disease activity index (DAI) score, including weight loss, colon shorten and histopathological abnormalities. The possible mechanism of PMNFs-attenuated colitis was investigated. The results showed that PMNFs reversed DSS-induced oxidative damage, and the antioxidant pathway Nrf2-keap1 signal was activated by PMNFs. Moreover, PMNFs suppressed the expression of pro-inflammatory factors including IL-1ß, TNF-α, IFN-ß and IL-6 via the inactivation of TLR4/NF-κB pathway in DSS-induced colitis and LPS-treated macrophage. Furthermore, PMNFs treatment prevented the reduction of tight junction proteins (ZO-1, occludin, and claudin-1) and mucin-2 (MUC-2) as well as the up-regulation of epithelial apoptosis caused by DSS. These findings demonstrate that the PMNFs against DSS-induced colitis due to its prevention on oxidative damage, inflammation, and intestine barrier breakdown. Thus, PMNFs have a potential application in the treatment of various oxidative stress or inflammation-related diseases.

Nitrogen-doped carbon dots from rhizobium as fluorescence probes for chlortetracycline hydrochloride.

Fluorescent nitrogen-doped carbon dots (CDs) were prepared via hydrothermal method at 190 °C for 10 h using rhizobium from soy as the carbon and nitrogen source. Their optical properties, structure, morphology, and functional groups were characterized in detail and the results showed that they possess unique excitation-dependent fluorescence behavior, with average diameter 4.5 ± 2.0 nm and good water dispersibility. Due to the overlap of the UV-vis absorbance of chlortetracycline hydrochloride (CCH) and the fluorescence excitation band of CDs, the fluorescence of the prepared CDs can be quenched by CCH selectively and sensitively. The changes of the fluorescence intensity of CDs have a good linear relationship with the concentration of CCH in a wide concentration range of 5-100 µM, with a detection limit of 0.254 µM. This present method has been successfully applied to determine the CCH in water with recovery ranging from 96.0% to 100.7%.

Ultrasonic synthesis of nano-PrO1.8 as nanozyme for colorimetric determination of trans-resveratrol.

In this study, nano-PrO1.8 were synthesized successfully in ionic liquids (ILs) as template assisted ultrasonic irradiation method. Various precipitating agents and different types of ILs were investigated to determine their respective effects on the morphology of the end products. Using hydrazine hydrate as a precipitating agent and 1-carboxymethyl-3-methylimidazolium chloride as a template, spherical structure with an average diameter of 250 nm was obtained. It is worth noting that the prepared material exhibits high peroxidase-like activity and weak oxidase activity. Then, the catalytic oxidation capacity of the nano-PrO1.8 was evaluated by the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB). The colorless of TMB can be converted into blue oxidized TMB (oxTMB) in the presence of nano-PrO1.8, but trans-resveratrol inhibited its peroxidase-like activity and weakened the blue color. Hence, we developed a sensitive, selective and simple colorimetric method for trans-resveratrol detection using nano-PrO1.8 as peroxidase-like enzyme. A linear relationship was found in the range of 0.30 µM-16 µM trans-resveratrol with the detection limit of 0.29 µM. Satisfactory results were achieved when the method was submitted to the determination of trans-resveratrol in white wine samples.

A highly selective chromogenic probe for the detection of nitrite in food samples.

A rapid, sensitive, and highly selective method for determining nitrite in food has been developed. This method is based on the reaction of nitrite with the amino group of 3,3,5,5-tetramethylbenzidine (TMB) to form a diazonium salt, and then the diazonium salt and glucosamine hydrochloride are coupled to each other to form an orange compound. The optimal conditions for maximum color and other analytical parameters were studied. A colorimetric method for nitrite detection has been developed with an outstanding correlation coefficient (R2 = 0.9944), a wide linear range (1-75 µM) and 0.73 µM limit of detection (at S/N = 3) for nitrite ions. This method was successfully applied to the determination of nitrite in a variety of foods and gave recoveries in the range between 100.16% and 103.07%, demonstrating that the accuracy, reliability and potential application of this assay for monitoring nitrite in foods.

A ratiometric fluorometric ciprofloxacin assay based on the use of riboflavin and carbon dots.

Carbon dots (CDs) were hydrothermally synthesized from selenious yeast. They were further coupled with riboflavin to form a dually emitting probe for ciprofloxacin (CIP). Under 370 nm excitation, the probe displays dual (blue and green) emissions with peaks at 443 and 510 nm. When CIP is added, the blue fluorescence of the CDs is enhanced while the green fluorescence remains unaffected. The ratio of the relative fluorescence intensities at 443 and 510 nm increases linearly in the 0.5-200 µM CIP concentration range. The fluorescent probe is selective and has a 0.13 µM detection limit. Satisfactory recoveries (97.9-101.1%) were received when the probe was used to quantify CIP in spiked water and human serum samples. Graphical abstractBlue-emissive carbon dots were prepared from selenious yeast via a hydrothermal method, and then coupled with riboflavin as a ratiometric fluorometric probe for ciprofloxacin determination.

Preparation of porous uranium oxide hollow nanospheres with peroxidase mimicking activity: application to the colorimetric determination of tin(II).

Porous uranium oxide hollow sphere nanoparticles were synthesized in ionic liquids under hydrothermal conditions. Various precipitating agents and ionic liquids were investigated to determine their respective impact on the resultant uranium oxide morphologies. Using hydrazine hydrate as precipitating agent and N-butyl pyridinium bromide as templating agent, a porous-hollow structure was created with a surface area of 1958 m2.g-1 and an average pore diameter of 30 nm. The nanoparticles revealed high peroxidase-mimicking activity. This was evaluated by using the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) that is catalytically oxidized by H2O2 to give oxidized TMB (oxTMB) which is blue (with an absorption peak at 652 nm). The material was used as a nanozyme for colorimetric detection of Sn2+. Meanwhile, it is found that BSA strongly improves the catalytic activity of the nanozyme, while Sn(II) inhibits its activity. Thus, a colorimetric method for Sn2+ detection was designed. The method works in the 0.5-100 µM Sn(II) concentration range and has a lower detection limit of 0.36 µM (at S/N = 3). Graphical abstract The catalytic activity of porous-hollow nano-UO2 toward the oxidation of 3,3',5,5'-tetramethylbenzidine by H2O2 is remarkably improved in the presence of bovine serum albumin, while tin(II) inhibits its activity. This finding has been applied to design a method for colorimetric quantification of tin(II) in water samples.

Downregulation of Glutathione S-transferase A1 suppressed tumor growth and induced cell apoptosis in A549 cell line.

Glutathione S-transferase A1 (GSTA1) is a phase II detoxification enzyme and serves a crucial role in anti-cancer drug resistance. In our previous study, GSTA1 was identified to be highly expressed in various subtypes of non-small-cell lung cancer cell lines compared with human embryonic lung fibroblast cell line MRC-5. The aim of the present study was to investigate the effect of GSTA1 expression on the proliferation and apoptosis of A549 cells. GSTA1 expression was knocked down or with overexpressed using lentivirus particles. Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to assess the protein, and mRNA levels of GSTA1 in A549 cells, respectively. The effect of GSTA1 manipulation on cell proliferation and apoptosis were investigated in vitro using MTT assays, Hoechst 33258 staining and flow cytometry, and in vivo using A549 cell line xenografts in nude mice. The results of the western blot analysis and RT-qPCR revealed that stable cell models of GSTA1 knockdown, and overexpression were established. The data of the MTT assay indicated that the downregulation of GSTA1 significantly inhibited cell proliferation compared with si-control-transfected cells. These si-GSTA1 A549 cells exhibited typical morphological changes of apoptosis, including chromatin condensation and shrunken nuclei compared with the si-control counterparts. An AnnexinV-fluorescein isothiocyanate assay verified that the downregulation of GSTA1 significantly induced cell apoptosis in vitro. In addition, overexpression of GSTA1 significantly promoted tumor growth in vivo. Accordingly, downregulation of GSTA1 suppressed tumor growth. In conclusion, GSTA1 plays an important role in regulation of cell proliferation and cell apoptosis in A549 cell line.

Curcumol induces apoptosis in SPC-A-1 human lung adenocarcinoma cells and displays anti-neoplastic effects in tumor bearing mice.

Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.

Effect of porcine Akirin2 on skeletal myosin heavy chain isoform expression.

Akirin2 plays an important role in skeletal myogenesis. In this study, we found that porcine Akirin2 (pAkirin2) mRNA level was significantly higher in fast extensor digitorum longus (EDL) and longissimus lumborum (LL) muscles than in slow soleus (SOL) muscle of pigs. Overexpression of pAkirin2 increased the number of myosin heavy chain (MHC)-positive cells, indicating that pAkirin2 promoted myoblast differentiation. We also found that overexpression of pAkirin2 increased the mRNA expressions of MHCI and MHCIIa and decreased the mRNA expression of MHCIIb. Myocyte enhancer factor 2 (MEF2) and nuclear factor of activated T cells (NFAT) are the major downstream effectors of calcineurin. Here we also observed that the mRNA expressions of MEF2C and NFATc1 were notably elevated by pAkirin2 overexpression. Together, our data indicate that the role of pAkirin2 in modulating MHCI and MHCIIa expressions may be achieved through calcineurin/NFATc1 signaling pathway.

Expression and function of GSTA1 in lung cancer cells.

Glutathione S-transferase A1 (GSTA1) appears to be primarily involved in detoxification processes, but possible roles in lung cancer remain unclear. The objective of this study was to investigate the expression and function of GSTA1 in lung cancer cells. Real-time PCR and Western blotting were performed to assess expression in cancer cell lines and the normal lung cells, then verify the A549 cells line with stable overexpression. Localization of GSTA1 proteins was assessed by cytoimmunofluorescence. Three double-strand DNA oligoRNAs (SiRNAs) were synthesized prior to being transfected into A549 cells with Lipofectamine 2000, and then the most efficient SiRNA was selected. Expression of the GSTA1 gene in the transfected cells was determined by real-time PCR and Western blotting. The viability of the transfected cells were assessed by MTT. Results showed that the mRNA and protein expression of A549 cancer cells was higher than in MRC-5 normal cells. Cytoimmunofluorescence demonstrated GSTA1 localization in the cell cytoplasm and/or membranes. Transfection into A549 cells demonstrated that down-regulated expression could inhibit cell viability. Our data indicated that GSTA1 expression may be a target molecule in early diagnosis and treatment of lung cancer.

[Effect of apigenin on proliferation and apoptosis of human lung cancer NCI-H460 cells].

OBJECTIVE: To study the effect of apigenin on the proliferation and apoptosis of human lung cancer cell line NCI-H460. METHODS: NCI-H460 cells were cultured with different concentrations of apigenin, and MTT assay was used to evaluate the cell inhibition rates. Apoptosis of NCI-H460 cells was observed under a fluorescence microscope with Hoechst 33258 staining and quantified by flow cytometry using annexin V-FITC/PI stain. The expressions of apoptosis-related proteins Bax, Bcl-2 and caspase-3 were analyzed by Western blotting. RESULTS: Apigenin causes concentration- and time-dependent inhibition of the proliferation of the cells. NCI-H460 cells treated with apigenin showed significant morphological changes of apoptosis, and the cell apoptotic rates increased as apigenin concentration increased. Western blotting demonstrated that apigenin increased the protein levels of Bax and caspase-3 and reduced the protein expression of Bcl-2. CONCLUSION: Apigenin can inhibit the proliferation and induce apoptosis of NCI-H460 cells possibly by up-regulating expression of Bax and caspase-3 and down-regulating the expression of Bcl-2.

[Lead adsorption by Trametes gallica, Bacillus cereus, and their co-immobilized biomaterial].

Taking Trametes gallica mycelium pellets, Bacillus cereus, and their co-immobilized biomaterial as bio-adsorbents, this paper studied their Pb2+ adsorption under effects of different contact time, medium initial pH value and Pb2+ concentration, and bio-adsorbent concentration, and compared the infrared spectra of the bio-adsorbents before and after Pb2+ absorption. The Pb2+ adsorption efficiency of the bio-adsorbents was the highest when the bio-adsorbent concentration was 2 g x L(-1), initial pH was 5.0, initial Pb2+ concentration was 50 mg x L(-1), and contact time was 1 h, with the Pb2+ biosorption rate being 71.7% for the mycelium pellets of T. gallica, 91.0% for B. cereus, and 96.9% for the co-immobilized biomaterial. The infrared spectra of the bio-adsorbents were mainly consisted of the absorption zones of protein, carbohydrates, and sulphur- and phosphors-based groups, suggesting that hydroxyl, carboxyl, and sulphur- and phosphate-based groups played important roles in the Pb2+ adsorption by the bio-adsorbents.

[Biosorption of crystal violet and malachite green by Rhodotorula graminis Y-5].

With a shaker, this paper studied the characteristics of the biosorption of crystal violet and malachite green by Rhodotorula graminis Y-5 under different adsorption time, initial pH, and temperature, as well as the desorption and recycling use of the dyes. The biosorption of crystal violet and malachite green by R. graminis Y-5 had the peaks (93.8% and 87.7%, respectively) at pH 7.0, dye concentration 50 mg x L(-1), 150 r x min(-1), 30 degrees C, and lasting 10 hours. After desorption, the biosorption rate of crystal violet and malachite green by R. graminis was 85.5% and 78.5%, respectively, indicating that the biosorption of crystal violet and malachite green was reversible, and the recycling use of the dyes by R. graminis was quite good, i. e., the dyes were renewable and could be recycled. Biosorption could be the mechanism of the decolorization of the dyes. The dyes were mostly adsorbed on the R. graminis surface -OH. The adsorption process was fast, efficient, and reversible, suggesting that R. graminis had a high potential for waste water treatment.

[Induce of laccase from Trametes gallica and its degradation on neutral dyes and organophosphorus pesticides].

The characteristics of the induction of laccase in Trametes gallica under different initial cultural pH, incubation time by different inducers were discussed, as well as the effects of temperature, pH and time on laccase degradation of six dyes and four organophosphors. The results showed that RB-bright blue, ABTS and o-toluidine affected the production of laccase at different levels, and ABTS was the best inductive agent in our test conditions, whose optimal initial pH and incubation time were 4.0 and 13 days, respectively. The appropriate reaction temperature of the laccase produced was 38 degrees C, and it got a good stability, for it could retain 78.6% of the enzyme activity after 20 min holding at 40 degrees C. Mediated by ABTS, the optimal temperature for laccase to degrade the six types of neutral dyes could be divided into two cases, that was 30 degrees C (neutral black, neutral bordeaux, neutral pink, methyl orange) and 60 degrees C (neutral dark yellow, cresol red), the optimal pH were 6.0 (neutral black), 2.0 (neutral bordeaux, neutral pink) and 4.0 (methyl orange, neutral dark yellow, cresol red), respectively, while the optimal times separately were 6 h (methyl orange, neutral dark yellow, cresol red), 12 h (neutral pink) and 24 h (neutral bordeaux). And using the same inductive agent, the best temperature for laccase to degrade dimethoate, chlorpyrifos, trichlorfon and parathion-pyridazine was 25 degrees C, the suitable time was 9 h, and the optimal pH was 10.0 for dimethoate, chlorpyrifos and parathion-pyridazine, and 8.0 for trichlorfon.