Quercetin, a typical flavonoid, possesses diverse biochemical and physiological actions, including antiplatelet, estrogenic, and anti-inflammatory properties. This review mainly centers on recent ten years findings with respect to intervening diabetes and its complications with the well-known flavonoid quercetin. After a short introduction of quercetin, major in vitro and in vivo findings are summarized showing that quercetin is a promising molecule for the treatment of these diseases. Finally, we contemplate future development and application prospects of quercetin. Despite the wealth of in animal research results suggesting the anti-diabetic and its complications potential of quercetin, its efficacy in diabetic human subjects is yet to be explored. The problem may become an important direction in the future research.
Abstract Background and Aims Therapeutic blockade of the programmed cell death protein‐1 (PD‐1) immune checkpoint pathways has resulted in significant reactivation of T cell–mediated antitumor immunity and is a promising clinical anticancer treatment modality in several tumor types, but the durable response rate remains relatively low (15%–20%) in most patients with HCC for unknown reasons. Evidence reveals that the interferon signaling pathway plays a critical role in modulating the efficacy and sensitivity of anti–PD‐1 therapy against multiple tumor types, but the mechanisms are unclear. Approach and Results Using Kaplan‐Meier survival analysis based on HCC databases, we found that deceased expression of interferon regulatory factor (IRF) 8 in HCC, among all the nine IRF members that regulate interferon signals, was associated with poor prognosis of patients with HCC. Moreover, gene set enrichment analysis identified the interferon‐gamma and PD‐1 signaling signatures as the top suppressed pathways in patients with IRF8‐low HCC. Contrarily, overexpression of IRF8 in HCC cells significantly enhanced antitumor effects in immune‐competent mice, modulating infiltration of tumor‐associated macrophages (TAMs) and T cell exhaustion in tumor microenvironment. We further demonstrated that IRF8 regulated recruitment of TAMs by inhibiting the expression of chemokine (C‐C motif) ligand 20 (CCL20). Mechanically, IRF8‐mediated repression of c‐fos transcription resulted in decreased expression of CCL20, rather than directly bound to CCL20 promoter region. Importantly, adeno‐associated virus 8–mediated hepatic IRF8 rescue significantly suppressed HCC progression and enhanced the response to anti–PD‐1 therapy. Conclusions This work identified IRF8 as an important prognostic biomarker in patients with HCC that predicted the response and sensitivity to anti–PD‐1 therapy and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.
Diabetes-associated male sexual dysfunction and fertility impairments are both common clinical complications with limited therapeutic options; hence it seriously affects the quality of life of the patients, in particular, the patients of reproductive age. Lycium barbarum polysaccharide (LBP) has long being believed to maintain and to promote reproductive functions in the traditional medical practice in China. The current study was to investigate if LBP may contribute to recovery of male sexual dysfunction and fertility impairments in diabetic individuals. The effects of LBP on sexual behaviors and histological changes of testis were studied in the type-1 diabetes male mice induced by intra-peritoneal (i.p.) injection of streptozotocin (STZ). After oral administration of LBP (10, 20 or 40 mg/kg), sildenafil citrate (SC, 5 mg/kg) or saline for 62 consecutive days, the typical abnormal changes in the sperm parameters, in relative weight of reproductive organs and in morphology of testis were observed in diabetic mice. LBP treatment of the diabetic mice considerably reversed those changes and Johnsen's testicular score, serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) level were also increased to different degrees. Moreover, our data have also shown that a marked improvement in sexual behavior and fertility level after administration of LBP (40 mg/kg) compared to the diabetic group. These results suggested that LBP can exert functional recovery of male sexual dysfunction and fertility damages induced by diabetes in male mice, which is likely to be mediated through regulating the hypothalamus- pituitary-gonadal axis endocrine activity.
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