A series of novel phthalocyanine‐doxorubicin (Pc‐DOX) conjugates have been prepared with a fibroblast activation protein (FAP)‐sensitive linker of glycine‐proline (Gly‐Pro) dipeptide. Meanwhile, two Pc‐DOX conjugates (1 c and 3 c) without FAP‐sensitive linker have also been prepared for comparison. For Pc‐DOX conjugates, the photosensitizing properties of the phthalocyanines are partly quenched after being conjugated with DOX. The aggregation behavior of these conjugates is less affected by the surfactant of Cremophor EL compared with that of corresponding precursors in aqueous media. The FAP‐responsive properties have been demonstrated by HPLC analysis and fluorescence spectroscopy in phosphate buffered saline. The Pc‐Gly‐Pro‐DOX conjugate 2 b with longer linker is more sensitive to FAP than the other two Pc‐Gly‐Pro‐DOX conjugates (1 b and 3 b). The results suggest that the longer linker and smaller steric hindrance between phthalocyanine and Dox units are beneficial for the cleavage of Gly‐Pro linker induced by FAP, while the axial or peripheral substituted positions hardly allow the enzymolysis of FAP. This work can thus provide a valuable reference for the targeted chemo‐photodynamic therapy of cancer.
Glyphosate is one of the most widely used herbicides
worldwide.
Unfortunately, the continuous use of glyphosate has resulted in serious
environmental contamination and raised public concern about its impact
on human health. In our previous study, Chryseobacterium sp. Y16C was isolated and characterized as an efficient degrader
that can completely degrade glyphosate. However, the biochemical and
molecular mechanisms underlying its glyphosate biodegradation ability
remain unclear. In this study, the physiological response of Y16C
to glyphosate stimulation was characterized at the cellular level.
The results indicated that, in the process of glyphosate degradation,
Y16C induced a series of physiological responses in the membrane potential,
reactive oxygen species levels, and apoptosis. The antioxidant system
of Y16C was activated to alleviate the oxidative damage caused by
glyphosate. Furthermore, a novel gene, goW, was expressed
in response to glyphosate. The gene product, GOW, is an enzyme that
catalyzes glyphosate degradation, with putative structural similarities
to glycine oxidase. GOW encodes 508 amino acids, with an isoelectric
point of 5.33 and a molecular weight of 57.2 kDa, which indicates
that it is a glycine oxidase. GOW displays maximum enzyme activity
at 30 °C and pH 7.0. Additionally, most of the metal ions exhibited
little influence on the enzyme activity except for Cu2+. Finally, with glyphosate as the substrate, the catalytic efficiency
of GOW was higher than that of glycine, although opposite results
were observed for the affinity. Taken together, the current study
provides new insights to deeply understand and reveal the mechanisms
of glyphosate degradation in bacteria.
The present study aimed to investigate the possible mechanisms underlying the effect of modified Xiaochaihu decoction (mXCHD) in the treatment of chronic hepatitis B (CHB). Patients with CHB, in addition to liver stagnation and spleen deficiency syndrome were randomly assigned to receive either Chinese (mXCHD) or western (entecavir) treatment, with 30 cases in each group. Serum was collected following treatment with mXCHD or entecavir for 7 days. A healthy group of 30 individuals was also included. HepG2.2.15 cells were cultured in vitro and randomly divided into four groups: Healthy; entecavir-treated; 10% mXCHD-treated; and 20% mXCHD-treated. The HepG2.2.15 cells in the four groups were treated with either serum from the healthy volunteers, entecavir-containing serum, or mXCHD-containing serum at different concentrations (10 or 20%, respectively). Following treatment with the corresponding serum, cell proliferation was examined using an MTT assay, and the expression of hepatitis B surface antigen (HBsAg) in the cell supernatant was detected using an enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Janus kinase (JAK)2 and signal transducer and activator of transcription (STAT)3 were measured using reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The results indicated that the most effective treatment for the promotion of HepG2.2.15 cell proliferation was a 20% concentration of mXCHD serum. The expression of HBsAg was significantly decreased in the groups treated with 10 and 20% mXCHD 48 h following intervention (P<0.01). The mRNA and protein expression levels of STAT3 in the 20% mXCHD serum group were significantly increased, compared with those in the healthy group (P<0.01 and P<0.05, respectively), whereas no significant difference was observed in the expression of JAK2 among the four groups. These results indicated that mXCHD suppressed the hepatitis B virus, and treatment of the cells with mXCHD-containing serum promoted HepG2.2.15 cell proliferation via modulating the expression of STAT3, which may contribute to the clinical efficacy of mXCHD against CHB.
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