ABSTRACT
Gout is a metabolic disorder characterized by elevated uric acid levels， often caused by purine metabolism disturbances or abnormalities in uric acid （UA） excretion. Currently， western medicine is the primary treatment approach for gout， but it often comes with significant side effects. Traditional Chinese medicine （TCM） has gained significant development in the field of gout treatment due to its safety and effectiveness. This article aimed to explore TCM strategies in the management of gout， providing insights for the development and application of TCM in the field of gout treatment. Relevant literature retrieved from PubMed， Web of Science， China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP databases was systematically analyzed with such keywords as "Chinese herbal medicine"， "traditional Chinese medicine"， "TCM"， and "gout". The findings suggest that TCM can treat gout through a syndrome differentiation approach that encompasses four pathological mechanisms： phlegm， blood stasis， dampness， and deficiency， simultaneously addressing both excess and deficiency syndromes in gout. Based on the pathological characteristics of four syndromes， namely dampness-heat retention， blood stasis-heat obstruction， phlegm-turbidity obstruction， and liver and kidney Yin deficiency， TCM adopts specific treatment approaches including clearing heat and promoting diuresis， activating blood and resolving stasis， resolving phlegm and reducing turbidity， and nourishing the liver and kidneys. These targeted approaches have proven to be effective in gout management. The main mechanisms of TCM in gout management include inflammation resistance ［regulating inflammatory pathways such as tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， interleukin-8 （IL-8）， and other chemokines， as well as inflammatory signaling pathways like nuclear factor-kappa B （NF-κB） and NOD-like receptor protein 3 （NLRP3）］， uric acid reduction （modulating uric acid transporters and inhibiting xanthine oxidase （XOD） activation）， antioxidant stress mitigation （suppressing reactive oxygen species and regulating nitric oxide， malondialdehyde， and other oxidative markers）， and immune system regulation.
ABSTRACT
BACKGROUND: Mesenchymal stem cells (MSCs) are an important component of the in vivo microenvironment and act on multiple biological behaviors of tumor cells. The potential clinical value of MSCs has become an issue of concern in recent years.OBJECTIVE: To investigate the gene expression profiles of acute promyelocytic leukemia (APL) cell line NB4 treated with umbilical cord-derived MSCs (UC-MSCs) using cDNA microarray.METHODS: In vitro co-culture system was constructed, and then cellular proliferation, apoptosis and differentiation status of NB4 cells treated with UC-MSCs were evaluated. Two cDNA probes were prepared through reverse transcription from mRNA of NB4 cells treated with or without UC-MSCs. The probes were labeled with fluorescence dyes individually, hybridized with cDNA microarray, and their fluorescent intensities were scanned. The genes were screened through the analysis of the difference in two gene expression profiles.RESULTS AND CONCLUSION: UC-MSCs promoted the proliferation and differentiation, while reduced the apoptosis of NB4 cells. The analysis of gene expression profiles indicated that after co-culture with UC-MSCs, 530 genes were up-regulated and 53 genes were down-regulated. Accordingly, specific gene function and pathway signaling related were also regulated to some extent. Overall, UC-MSCs influence can major biological behaviors of NB4 cells by changing expression of a large amount of genes, gene-related function and multiple intracellular signaling pathways.
ABSTRACT
BACKGROUND: Imatinib has a significant pro-apoptosis effect on chronic myelogenous leukemia (CML), but there are still some patients being resistant to it. Human umbilical cord mesenchymal stem cells (hUC-MSCs) affect the apoptosis of a variety of hematologic malignancies. However, the impacts of hUC-MSCs on the apoptosis of CML cells induced by imatinib remain unclear.OBJECTIVE: To investigate whether hUC-MSCs have an influence on the apoptosis of K562 cells induced by imatinib and to reveal the possible underlying mechanism.METHODS: K562 cells were cultured with hUC-MSCs or/and imatinib. Cellular apoptosis was measured with Annexin-V and PI staining by flow cytometry analysis. The protein expressions of Bax, Bcl-2, caspase-3, caspase-9 and cleaved-PARP in K562 cells were detected by western blot assay. Pan-caspase inhibitor Z-VAD-FMK was used to block apoptosis in each group, and during this process the effect of caspase apoptosis signaling pathway was detected.RESULTS AND CONCLUSION: The apoptosis of K562 cells was enhanced, when imatinib was combined with hUC-MSCs. Western blot analysis showed that the expression of pro-apoptotic protein Bax was enhenced and the expression of anti-apoptotic protein Bcl-2 was suppressed. Furthermore, the cleaved forms of caspase-9, caspase-3 and PARP in K562 cell were higher in the hUC-MSCs+imatinib group than in the imatinib group. The apoptosis of K562 cells induced by the hUC-MSCs combined with imatinib was significantly inhibited by Z-VAD-FMK. In conclusion, these findings indicate that hUC-MSCs can enhance imatinib-induced apoptosis of K562 cells by activating caspase apoptosis signaling pathway.