Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

To investigate the cytotoxicity of the homemade peptide cationic liposome CDO14 and its efficacy of RNA interference (RNAi). MTT method was used to determine the cytotoxicity of the liposome to a human lung cancer cell line Luc-A549 that can express luciferase stably. Luciferase siRNA (Luc-siRNA) was transfected into Luc-A549 cells by CDO14. Contents of luciferase in the transfected cells were detected by luminous instrument and contents of total protein in these cells were detected by BCA method. Nude mice were inoculated with Luc-A549 cells in axilla to establish xenograft tumor model. Complexes of Luc-siRNA and the cationic liposomes were injected into the modeling mice via tail vein. Contents of luciferase in the transfected mice were detected by the whole body imaging system. The cytotoxicity of the homemade cationic liposome was similar to that of commercial liposome DOTAP, and lower than that of Lipo2000. The siRNA transfection efficacy mediated by CDO14 was higher than that mediated by DOTAP. The homemade peptide cationic liposome CDO14 is expected to serve as delivery vector in gene therapy because of its low cytotoxicity and high transfection efficiency.
Animals ; Cations ; Cell Line, Tumor ; Fatty Acids, Monounsaturated ; Genetic Therapy ; Genetic Vectors ; Humans ; Liposomes ; Luciferases ; Lung Neoplasms ; Mice ; Mice, Nude ; Peptides ; Quaternary Ammonium Compounds ; RNA Interference ; RNA, Small Interfering ; Transfection

OBJECTIVETo develop a resin composite incorporated with nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt, and to measure its effect on human dental plaque microcosm biofilm.

METHODSA novel nano-antibacterial inorganic filler containing long-chain alkyl quaternary ammonium salt was synthesized according to methods introduced in previous research. Samples of the novel nano-antibacterial inorganic fillers were modified by a coupling agent and then added into resin composite at 0%, 5%, 10%, 15% or 20% mass fractions; 0% composite was used as control. A flexural test was used to measure resin composite mechanical properties. Results showed that a dental plaque microcosm biofilm model with human saliva as inoculum was formed. Colony-forming unit (CFU) counts, lactic acid production, and live/dead assay of biofilm on the resin composite were calculated to test the effect of the resin composite on human dental plaque microcosm biofilm.

RESULTSThe incorporation of nano-antibacterial inorganic fillers with as much as 15% concentration into the resin composite showed no adverse effect on the mechanical properties of the resin composite (P > 0.05). Resin composite containing 5% or more nano-antibacterial inorganic fillers significantly inhibited the metabolic activity of dental plaque microcosm biofilm, suggesting its strong antibacterial potency (P < 0.05).

CONCLUSIONThis novel resin composite exhibited a strong antibacterial property upon the addition of up to 5% nano-antibacterial inorganic fillers, thereby leading to effective caries inhibition in dental application.

Anti-Bacterial Agents ; pharmacology ; Biofilms ; drug effects ; Composite Resins ; chemistry ; Dental Caries ; prevention & control ; Dental Plaque ; Humans ; Lactic Acid ; Quaternary Ammonium Compounds ; pharmacology ; Saliva

Antibacterial adhesives are promising to inhibit biofilms and secondary caries. The objectives of this study were to synthesize and incorporate quaternary ammonium methacrylates into adhesives, and investigate the alkyl chain length effects on three-dimensional biofilms adherent on adhesives for the first time. Six quaternary ammonium methacrylates with chain lengths of 3, 6, 9, 12, 16 and 18 were synthesized and incorporated into Scotchbond Multi-Purpose. Streptococcus mutans bacteria were cultured on resin to form biofilms. Confocal laser scanning microscopy was used to measure biofilm thickness, live/dead volumes and live-bacteria percentage vs. distance from resin surface. Biofilm thickness was the greatest for Scotchbond control; it decreased with increasing chain length, reaching a minimum at chain length 16. Live-biofilm volume had a similar trend. Dead-biofilm volume increased with increasing chain length. The adhesive with chain length 9 had 37% live bacteria near resin surface, but close to 100% live bacteria in the biofilm top section. For chain length 16, there were nearly 0% live bacteria throughout the three-dimensional biofilm. In conclusion, strong antibacterial activity was achieved by adding quaternary ammonium into adhesive, with biofilm thickness and live-biofilm volume decreasing as chain length was increased from 3 to 16. Antibacterial adhesives typically only inhibited bacteria close to its surface; however, adhesive with chain length 16 had mostly dead bacteria in the entire three-dimensional biofilm. Antibacterial adhesive with chain length 16 is promising to inhibit biofilms at the margins and combat secondary caries.
Anti-Bacterial Agents ; pharmacology ; Biofilms ; Methacrylates ; pharmacology ; Microscopy, Confocal ; Quaternary Ammonium Compounds ; pharmacology

Ammonium perchlorate (AP), mainly used as solid propellants, was reported to interfere with homeostasis via competitive inhibition of iodide uptake. However, detailed mechanisms remain to be elucidated. In this study, AP was administered at 0, 130, 260 and 520 mg/kg every day to 24 male SD rats for 13 weeks. The concentrations of iodine in urine, serum thyroid hormones levels, total iodine, relative iodine and total protein, and malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activity in thyroid tissues were measured, respectively. Our results showed that high-dose perchlorate induced a significant increase in urinary iodine and serum thyroid stimulating hormone (TSH), with a decrease of total iodine and relative iodine content. Meanwhile, free thyroxine (FT4) was decreased and CAT activity was remarkably increased. Particularly, the CAT activity was increased in a dose-dependent manner. These results suggested that CAT might be enhanced to promote the synthesis of iodine, resulting in elevated urinary iodine level. Furthermore, these findings suggested that iodine in the urine and CAT activity in the thyroid might be used as biomarkers for exposure to AP, associated with thyroid hormone indicators such as TSH, FT4.
Analysis of Variance ; Animals ; Catalase ; metabolism ; Dose-Response Relationship, Drug ; Homeostasis ; drug effects ; Iodine ; metabolism ; urine ; Male ; Malondialdehyde ; metabolism ; Perchlorates ; pharmacology ; Quaternary Ammonium Compounds ; pharmacology ; Radioimmunoassay ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Thyroid Gland ; metabolism ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVEThis study aimed to synthesize a novel nano-antibacterial inorganic filler that contains a quaternary ammonium salt with long chain alkyl and to report the antibacterial property of dental resin composites.

METHODSA novel nano-antibacterial inorganic filler that contains a quaternary ammonium salt with long chain alkyl was synthesized based on previous research. The antibacterial property of the filler was measured. The surface of the novel nano-antibacterial inorganic filler was modified by a coupling agent to achieve a good interfacial bonding between the filler and the resin matrix. Infrared spectrum analysis was carried out. The modified novel nano-antibacterial inorganic fillers were then incorporated into the dental resin matrix. The dispersion of the fillers was observed and compared with those incorporated into Tetric N-Ceram, a commercial resin composite, under a scanning electron microscope. Streptococcus mutans was used in testing the antibacterial property of the dental resin composites.

RESULTSA quaternary ammonium salt with a long chain alkyl was successfully grafted onto the surface of nano-silica particles. The novel nano-antibacterial inorganic filler that contains quaternary ammonium salt with a long chain alkyl showed stronger antibacterial efficacy than the antibacterial inorganic filler that contains quaternary ammonium salt with a short chain alkyl. The modified novel antibacterial inorganic fillers displayed a homogeneous dispersion in the resin composite bulk and combined closely with the resin matrix, similar to the Tetric N-Ceram. The resin composites that contain novel antibacterial inorganic fillers showed stronger antibacterial effect on Streptococcus mutans compared with the control group.

CONCLUSIONThe novel nano-antibacterial inorganic filler that contains a quaternary ammonium salt with long chain alkyl showed a strong antibacterial property. It also exhibited good compatibility with the dental resin matrix after undergoing coupling treatment.

Acrylic Resins ; Anti-Bacterial Agents ; Composite Resins ; Polyurethanes ; Quaternary Ammonium Compounds ; Streptococcus mutans

Natural toxic substances have a bitter taste and their ingestion sends signals to the brain leading to aversive oral sensations. In the present study, we investigated chronological changes in c-Fos immunoreactivity in the nucleus tractus solitarius (NTS) to study the bitter taste reaction time of neurons in the NTS. Equal volumes (0.5 mL) of denatonium benzoate (DB), a bitter tastant, or its vehicle (distilled water) were administered to rats intragastrically. The rats were sacrificed at 0, 0.5, 1, 2, 4, 8, or 16 h after treatment. In the vehicle-treated group, the number of c-Fos-positive nuclei started to increase 0.5 h after treatment and peaked 2 h after gavage. In contrast, the number of c-Fos-positive nuclei in the DB-treated group significantly increased 1 h after gavage. Thereafter, the number of c-Fos immunoreactive nuclei decreased over time. The number of c-Fos immunoreactive nuclei in the NTS was also increased in a dose-dependent manner 1 h after gavage. Subdiaphragmatic vagotomy significantly decreased DB-induced neuronal activation in the NTS. These results suggest that intragastric DB increases neuronal c-Fos expression in the NTS 1 h after gavage and this effect is mediated by vagal afferent fibers.
Adjuvants, Immunologic/pharmacology ; Afferent Pathways/physiology ; Animals ; Injections/veterinary ; Ligands ; Male ; Proto-Oncogene Proteins c-fos/*metabolism ; Quaternary Ammonium Compounds/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled/*metabolism ; Solitary Nucleus/*physiology ; Vagus Nerve/*drug effects/*physiology

We in the present study observed the effect of N-fructose modified chitosan quaternary ammonium derivatives on on rat skin wound healing through animal experiments. Forty rats were randomly divided into eight groups (5 in each group). Four groups among the all 8 groups were the experimental groups, while the other 4 groups were the control groups. Next to the skin along the back of the spine, 1.50 cm x 2.00 cm x 0.16 cm full-thickness skin was cut to make an excision wound model for every rat. Those in the experimental groups were treated with the N-fructose-modified chitosan quaternary ammonium derivatives ointment dressing the wound, while those in the control groups with sterile medical vaseline processing. We dressed the wounds twice a day to observe the wound healing of all rats in different groups. We then observed the wound healing and wound pathology after 3, 7, 10, 15 days re spectively in different groups. Results showed significant differences of the time of wound healing, area of wound healing and volume of wound healing between the experimental groups and control groups (P < 0.05). It can be well concluded that N-fructose-modified chitosan quaternary ammonium derivatives does not harm the skin, but could promote skin healing, so that they could be suitable skin repair materials and ideal raw materials for medical dressing.
Animals ; Bandages ; Chitosan ; therapeutic use ; Polymers ; therapeutic use ; Quaternary Ammonium Compounds ; therapeutic use ; Rats ; Skin ; pathology ; Wound Healing

OBJECTIVETo investigate the mechanism of thyroid cytotoxicity mechanism of ammonium perchlorate (AP).

METHODSThyroid cells were cultured in vitro to a certain stage and then exposed to AP (0, 5, 10, 20, 40, and 60 mmol/L) in culture solution; the cultured cells and supernatant were collected. Cell viability was measured by MTT assay; cell apoptosis was determined by flow cytometry; the concentration of thyroglobulin was measured by enzyme-linked immunosorbent assay; the lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, and so on were measured by colorimetry.

RESULTSThe cells exposed to 60 mmol/L AP for 12, 24, 48, and 72 h had cell viabilities of 74.93%, 42.26%, 2.66%, and 0.99%, respectively, and the cells exposed to 40 mmol/L AP for 24, 48, and 72 h had cell viabilities of 73.15%, 30.91%, and 3.03%, respectively, all significantly lower than that of the control group (100%)(P < 0.05 or P < 0.01). The overall apoptosis rate of all AP-exposed cells was significantly higher than that of the control group; the cells exposed to 20, 40, and 60 mmol/L AP had early apoptosis rates of 15.70%, 15.84%, and 16.96%, respectively, significantly higher than that of the control group (9.54%)(P < 0.05 or P < 0.01); the cells exposed to 60 mmol/L AP had a late apoptosis rate of 16.54%, significantly higher than that of the control group (6.11%)(P < 0.05 or P < 0.01). The cells exposed to 40 mmol/L AP had a significantly higher LDH activity than the control group (0.70 U/ml vs 0.55 U/ml, P < 0.01). The cells exposed to 5 mmol/L AP had a significantly higher MDA level than the control group (1.08 mmol/L vs 2.36 mmol/L, P < 0.05).

CONCLUSIONAP can markedly change the cell morphology and decrease the cell viability of thyroid cells, which may be because AP inhibits cell proliferation, induces cell apoptosis, and destroys cell membranes. However, AP does not result in significant oxidative damage to thyroid cells.

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Humans ; Oxidative Stress ; Perchlorates ; toxicity ; Quaternary Ammonium Compounds ; toxicity ; Thyroglobulin ; metabolism ; Thyroid Gland ; drug effects ; metabolism ; pathology

OBJECTIVETo study the effect of nitrogen forms on nitrogen metabolism and main chemical composition of Pinellia ternate.

METHODThrough the soilless cultivation experiment and based at the same nitrogen level and different NH4(+) -N/NO3(-) -N ratios, nitrate reductase (NR) activity, glutamine synthetase (GS) activity, the content of nitrate nitrogen and ammonium nitrogen in different parts of P. ternate were determined. The contents of total alkaloid, free total organic acids and guanosine in the tuber were determined. The yield of bulbil and tuber was calculated.

RESULTThe test results showed that, with the NH4(+) -N/NO3(-) -N ratio increasing, the activity of nitrate reductase decreased, the content of nitrate nitrogen in the leaves, petioles and tuber increasing initially, then decreased, and the content of nitrate nitrogen in the root decreased. Meanwhile, with the NH4(+) -N/NO3(-) -N ratio increasing, the activity of glutamine synthetase in the leaves, petioles and root increased, the activity of glutamine synthetase in the tuber increasing initially, then decreased. The contents of ammonium nitrogen in the leaves, tuber and root increased initially, then decreased, and the contents of ammonium nitrogen in the petioles increased with the NH4(+)(-N/NO3(-)-N ratio increasing. The yield of bulbil and tuber were the highest at the NH4(+)-N/NO3(-) -N ratio of 75: 25. The content of total alkaloid and guanosine in the tuber were the highest at the NH4(+)-N/NO3(-) -N ratio of 0: 100, and the contents were 0.245% and 0.0197% respectively. With the NH4(+)-N/NO3(-) -N ratio of 50: 50, the content of free total organic acids was the highest, it reached 0.7%, however, the content of free total organic acids was the lowest at the NH4(+) -N/NO3(-) -N ratio of 0: 100.

CONCLUSIONNitrogen fertilization significant influences the nitrogen metabolism, the yield and main chemical composition of P. ternate.

Fertilizers ; analysis ; Nitrates ; analysis ; Nitrogen ; metabolism ; Pinellia ; chemistry ; growth & development ; metabolism ; Quaternary Ammonium Compounds ; analysis