Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extra

Toxicokinetics plays a crucial role in the health risk assessments of xenobiotics. Classical compartmental models are limited in their ability to determine chemical concentrations in specific organs or tissues, particularly target organs or tissues, and their limited interspecific and exposure route extrapolation hinders satisfactory health risk assessment. In contrast, physiologically based toxicokinetic (PBTK) models quantitatively describe the absorption, distribution, metabolism, and excretion of chemicals across various exposure routes and doses in organisms, establishing correlations with toxic effects. Consequently, PBTK models serve as potent tools for extrapolation and provide a theoretical foundation for health risk assessment and management. This review outlines the construction and application of PBTK models in health risk assessment while analyzing their limitations and future perspectives.

Background: Diabetes aggravates cerebral ischemia/reperfusion (I/R) injury by increasing inflammatory reactions, but its specific mechanism is currently unclear. Material/Methods: Diabetes was induced in mice with a high-fat diet combined with streptozotocin. These mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min, followed by reperfusion for 24-72 h and post-treatment glycyrrhizic acid (GA). Control and diabetic mice were randomly allocated to 8 groups of 18 mice each. Blood glucose, brain infarction, brain edema, and neurological function were monitored. Necrosis was determined by Nissl staining, loss of neurons by immunofluorescent (IF) staining for NeuN, and activation of inflammatory microglia by IF staining for Iba-1. Levels of HMGB1, TLR4, Myd88, and NF-kappa B mRNA and protein in ischemic brain were determined by qRT-PCR and western blotting, respectively, and serum concentrations of IL-1 beta, IL-6, and TNF-alpha by ELISA. Results: Infarction volume, brain edema, and neurological function after tMCAO were significantly aggravated in diabetes, but ameliorated by post-treatment GA. GA also reduced neuronal loss and microglial activation. Cerebral Myd88 level showed a positive correlation with neurological scores. GA suppressed the expression of Myd88 and a proinflammatory pathway that included Myd88, HMGB1, TLR4, and NF-kappa B, as well as reducing serum concentrations of IL-1 beta, IL-6, and TNF-alpha. Conclusions: Post-treatment inhibited inflammatory responses and provided therapeutic benefits in diabetic mice with cerebral I/R injury, suggesting that GA may be a candidate drug to suppress cerebral I/R in diabetic patients.

Isocitrate dehydrogenase1 (IDH1) mutation is the most important genetic change in glioma. The most common IDH1 mutation results in the amino acid substitution of arginine 132 (Arg/R132), which is located at the active site of the enzyme. IDH1 Arg132His (R132H) mutation can reduce the proliferative rate of glioma cells. Numerous diseases follow circadian rhythms, and there is growing evidence that circadian disruption may be a risk factor for cancer in humans. Dysregulation of the circadian clock serves an important role in the development of malignant tumors, including glioma. Brain‑Muscle Arnt‑Like protein 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK) are the main biological rhythm genes. The present study aimed to further study whether there is an association between IDH1 R132H mutation and biological rhythm in glioma, and whether this affects the occurrence of glioma. The Cancer Genome Atlas (TCGA) database was used to detect the expression levels of the biological rhythm genes BMAL1 and CLOCK in various types of tumor. Additionally, U87‑MG cells were infected with wild‑type and mutant IDH1 lentiviruses. Colony formation experiments were used to detect cell proliferation in each group, cell cycle distribution was detected by flow cytometry and western blotting was used to detect the expression levels of wild‑type and mutant IDH1, cyclins, biological rhythm genes and Smad signaling pathway‑associated genes in U87‑MG cells. TCGA database results suggested that BMAL1 and CLOCK were abnormally expressed in glioma. Cells were successfully infected with wild‑type and mutant IDH1 lentiviruses. Colony formation assay revealed decreased cell proliferation in the IDH1 R132H mutant group. The cell cycle distribution detected by flow cytometry indicated that IDH1 gene mutation increased the G₁ phase ratio and decreased the S phase ratio in U87‑MG cells. The western blotting results demonstrated that IDH1 R132H mutation decreased the expression levels of the S phase‑associated proteins Cyclin A and CDK2, and increased the expression levels of the G₁ phase‑associated proteins Cyclin D3 and CDK4, but did not significantly change the expression levels of the G₂/M phase‑associated protein Cyclin B1. The expression levels of the positive and negative rhythm regulation genes BMAL1, CLOCK, period (PER s (PER1, 2 and 3) and cryptochrom (CRY)s (CRY1 and 2) were significantly decreased, those of the Smad signaling pathway‑associated genes Smad2, Smad3 and Smad2‑3 were decreased, and those of phosphorylated (p)‑Smad2, p‑Smad3 and Smad4 were increased. Therefore, the present results suggested that the IDH1 R132H mutation may alter the cell cycle and biological rhythm genes in U87‑MG cells through the TGF‑β/Smad signaling pathway.

Based on semi-interpenetrating polymer network (semi-IPN) hydrogel films, a multiple stimuli-responsive film system composed of poly(acrylic acid) (PAA) and N,N-diethyl acrylamide (DEA), designated as PAA–PDEA semi-IPN films, was realized on a glassy carbon (GC) electrode surface with a one-step polymerization method. Rutin (RT), an electroactive probe, displayed invertible pH-, thermo- and SO₄ ²⁻ concentration–sensitive cyclic voltammogram (CV) behaviors in the film system. This multiply sensitive electrocatalysis of RT at the PAA–PDEA films was employed to further investigate the multiple stimuli-responsive ON–OFF behaviors of RT. The scanning electron microscopy (SEM) images and control experiments showed pH-sensitive ON–OFF properties of RT, which could be ascribed to the protonated/deprotonated carboxylic (–COOH) groups of the PAA component in different pH buffers and the properties of RT itself. However, the confirmation change or phase transition of the PDEA hydrogel film between the coil and globular states led to thermo- and SO₄ ²⁻ concentration–sensitive ON–OFF properties. According to these results, a 3-input/3-output logic gate and a 2-to-1 encoder were constructed successfully. This present system was fabricated for the first time, which may offer numerous possibilities for the design of new electrochemical drug sensors, drug-mimicking release processes and other medical applications. Furthermore, it also can contribute to the development of biomolecular or molecular computing.