This study aimed to investigate whether the anti-tumor effect of gemcitabine (GEM) in non-small-cell lung cancer (NSCLC) treatment was affected by Danggui Buxue decoction (DBD), and explore the potential mechanisms. The combined use of GEM and DBD showed an enhanced tumor growth inhibition effect in a murine Lewis lung carcinoma (LLC) model. LC-MS/MS results showed that the pharmacokinetic behaviors of a GEM active metabolite, gemcitabine triphosphate (dFdCTP), were found to be altered remarkably in the peripheral blood mononuclear cells (PBMC) of DBD co-administration rats. In addition, after co-administration of DBD with GEM, Western Blot and qPCR results confirmed that the expression of deoxycytidine kinase (dCK) in tumor tissues of LLC-bearing mice were markedly increased. DBD co-administration also reversed the upregulation of P-glycoprotein (P-gp) in tumor tissues induced by GEM. Moreover, DBD could notably up-regulate the IL-12p70 and GM-CSF expression in mice serum, suggesting potential immunomodulatory activities in tumor-bearing mice. Meanwhile, DBD inhibited the P-gp efflux activity in A549 cells. Therefore, the regulation of dCK and P-gp played important roles in the alternation of GEM pharmacokinetics and the enhancement of the anti-tumor effect of GEM. DBD being a potential dCK promoter could work as an adjuvant agent to boost the anticancer effect of GEM.

Background: Porphyromonas gingivalis ( P. gingivalis ) has been found to enter the brain and induce inflammation, contributing to Alzheimer's disease (AD). P. gingivalis is also closely linked to gut dysbiosis. However, does P. gingivalis induce AD-like pathology through the microbiota-gut-brain axis? There is limited literature on this topic. Objective: To determine the precise causal link among P. gingivalis , intestinal inflammation, and AD-related pathology. Methods: 12- to 13-month-old female C57BL/6J mice were subjected to ligature placement and oral administration of P. gingivalis over a 24-week period. Then, cognitive performance was evaluated with behavioral tests, while AD neuropathological changes, neuroinflammation, and intestinal inflammation were assessed through qPCR, immunofluorescence, and western blot, and gut microbiota was analyzed by 16S rRNA. Results: Mice exposed to P. gingivalis showed impaired behavior in open field test, novel object recognition, and Y-maze tests. The bacterium infiltrated their brains, increasing Aβ ₄₂ , AβPP, and Aβ fragments, promoting tau phosphorylation and microglial activation, and reducing levels of ZO-1, PSD95, SYP, and NeuN proteins. Inflammatory factors like NLRP3, caspase-1, IL-1β, IL-6, and TNF-α were elevated in both brains and intestine, while ZO-1 and occludin levels decreased in intestine. P. gingivalis also altered gut microbial compositions. Conclusions: P. gingivalis induced gut dysbiosis and activated the NLRP3 inflammasome in the intestine and brains of mice. This led to impairment of both the intestinal and brain-blood barriers, triggering neuroinflammation and promoting the progression of AD. These findings highlight the critical role of NLRP3 inflammasome activation in the microbiota-gut-brain axis in the AD-like pathology induced by P. gingivalis.

A suitable liquid chromatography quadrupole time-of-flight mass spectrometric (LC-Q-TOF-MS) method was developed for separation and characterization of related substances in bacitracin test drug. The separation was performed on LiChrospher RP-18 column using methanol as mobile phase A and 0.2% ammonium acetate buffer solution as mobile phase B in gradient elution. A total of 12 related substances were detected through high resolution mass spectrometric determination in a positive electrospray ionization mode. They were identified as co-existing active components and degradation products of bacitracin through the analysis and elucidation of both the protonated parents and the product ions of all the related substances and their fragmentation pathways were also proposed.