Resveratrol (RSV) has been reported to influence many biological processes, including the stimulation of cellular senescence and inhibition of epithelial-mesenchymal transition (EMT). In this research, we explored the mechanisms of RSV on EMT and cellular senescence through the expression of a DNA damage response (DDR) protein, Rad9, in breast and lung cancer cell lines. Upon treating breast and lung cancer cell lines with RSV at the concentrations of 10–50 μM, Rad9 expression was increased at both transcriptional and translational levels. The results indicated that RSV-induced Rad9 expression, mediated by DNA damage and ROS, can significantly suppress proliferation by activating cellular senescence, and diminishing the expression of EMT markers with concomitant downregulation of Slug in breast and lung cancer cell lines. By using a siRNA approach, RSV was shown to mediate cellular senescence and EMT through a Rad9-dependent mechanism. The treatment with RSV can inhibit the proliferation, EMT, and increase cellular senescence of breast and lung cancer cell lines by activating Rad9. Our results suggest that the breast and lung tumor suppressive activities of RSV are, at least in part, mediated by the upregulation of Rad9.
The complete mLF cDNA (GenBank: EU523857) encoded a 710-aa precursor with a 19-aa signal peptide. The nucleotide sequence of mLF showed the highest identity to the rhesus monkey LF (98%), whereas the putative amino acid sequence of mLF showed the highest identity to the hLF (90%). The rmLF and natural hLF showed almost equivalent antibacterial activities against Klebsiella pneumoniae and mLF presented a slightly lower activity against Listeria monocytogenes than natural hLF. In addition, the patterns of iron release from mLF and hLF were nearly identical.
Abstract5-Aminolevulinic acid (5-ALA) is a non-proteinogenic amino acid which has involved in heme metabolism of organisms, and has been widely applied in agriculture, and medical fields nowadays. 5-ALA is used in the elimination of pathogens or cancer cells by photodynamic therapy (PDT) owing to the photosensitizer reaction which releases the reactive oxygen species (ROS). Currently, biofabrication of 5-ALA is regarded as the most efficient and eco-friendly approach, but the complicated ingredient of medium causes the nuisance process of purification, resulting in low recovery and high producing cost. In this study, hydrogen chloride, sodium acetate, and ammonia were examined to maximize the recovery of 5-ALA from ion-exchange chromatography (IEC), thus a 92% recovery in 1 M ammonia at pH 9.5 was obtained. Afterward, the activated carbon was used for decolorization to further remove the pigments from the eluent. Four organic solvents, i.e., diethyl ether, methanol, ethanol, and acetone were compared to extract and form 5-ALA precipitation. The purified 5-ALA was verified to eliminate 74% of A549 human lung cancer and 83% of A375 melanoma skin cancer cell. Moreover, Proteus hauseri, Aeromonas hydrophila, Bacillus cereus, and Staphylococcus aureus were killed via anti-microbial PDT with 1% 5-ALA and reached 100% killing rate at optimal condition. With the addition of 0.05% 5-ALA during the culture, the growth of microalgae Chlorella sorokiniana was improved to against a common aquatic pathogen, A. hydrophila. The broad application of 5-ALA was demonstrated in this study for the first time. Graphical Abstract
Glaucoma is the leading cause of irreversible blindness due to increased intraocular pressure (IOP) in the eye. We have developed a novel treatment option for glaucoma based on a real-time IOP-dependent nitric oxide synthase (NOS) and packed in a therapeutic contact lens to reduce the IOP. First, 1.6 nmole nitric oxide was produced from the genetic chassis, which was optimized for isopropyl β-d-1-thiogalactopyranoside (IPTG) induction in a T7 expression system. For biosafety concerns to human being, the csgAD genes responsible for curli biofilm formation in Escherichia coli were co-expressed with NOS in the designated NOSAD strain to strengthen the adherence of cells to the contact lens, thereby preventing the contamination into the eyes. Moreover, NOSAD is a diaminopimelic acid (DAP) auxotrophic strain, which cannot survive without supplementation of DAP and reached the critical consideration of biosafety to the environment. We also demonstrated that the nitric oxide diffusion was 3.6-times enhanced from penetration into the aqueous humor of porcine eyes. The deformation ratio of the contact lens was correlated to the change of IOP by using a digital image correlation (DIC) system in a porcine eye model. The novel systematic approach provides an alternative treatment for glaucoma patients in the future.
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