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Rhamnan sulphate (RS) is a sulphated polysaccharide found in green algae such as Monostroma nitidum that exhibits various biological functions, including anticoagulant, antitumour, antiviral, and anti‐obesity properties. In our previous clinical trial, we demonstrated that RS intake improves constipation. However, no specific bacteria showed a significant (p <.05) change. Notably, these results were obtained after a short RS inoculation period of only 2 weeks. In the present study, to evaluate the long‐term effects of RS on the gut microbiota, we orally administered RS to BALB/c mice for 11 weeks, analyzed their blood biochemical data, and performed 16s rRNA‐sequencing. Oral administration of RS increased body weight with increased food intake, whereas plasma total cholesterol and fasting plasma glucose levels decreased. RS‐fed mice showed lower fasting insulin levels (p <.1) and decreased homeostatic model assessment for insulin resistance (HOMA‐IR, p <.0001), suggesting that RS improved insulin resistance. In the feces of mice, the amounts of acetic and propionic acids increased. In the gut microbiota, predictive metagenomic profiling using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) revealed functional alterations in Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways in RS‐fed mice. Corresponding to the blood glucose‐lowering effect, the glycolysis and tricarboxylic acid (TCA) cycle pathways were activated. In addition, the Firmicutes/Bacteroides (F/B) ratio, which may be associated with various health outcomes, was also reduced. These results suggest that the blood glucose‐lowering effect, improvement in insulin resistance, and lipid‐lowering effect of RS may be due to changes in the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter, which has been identified as a prognostic marker in several types of cancer, including pancreatic cancer. However, to the best of our knowledge, the association between SLC20A1 expression and cancer stem cell (CSC) markers, such as aldehyde dehydrogenase 1 (ALDH1), in pancreatic ductal adenocarcinoma (PDAC), and the role of SLC20A1 in PDAC CSCs remains unclear. In the present study, a genomic dataset of primary pancreatic cancer (The Cancer Genome Atlas, Pan-Cancer Atlas) was downloaded and analyzed. Kaplan-Meier analysis and multivariate Cox regression analysis were performed to evaluate the overall survival, disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI). Subsequently, SLC20A1 small interfering RNA (siRNA) knockdown (KD) was induced in the PANC-1 and MIA-PaCa-2 PDAC cell lines, and in sorted high ALDH1 activity (ALDH1high) cells, after which, cell viability, in vitro tumor sphere formation, cell death and caspase-3 activity were examined. The results revealed that patients with high expression of SLC20A1 (SLC20A1high) at tumor stage I had a poor prognosis compared with patients with low expression of SLC20A1 (SLC20A1low) in terms of DSS, DFI and PFI. In addition, patients with high expression of SLC20A1 and ALDH1A3 (SLC20A1highALDH1A3high) exhibited poorer clinical outcomes than patients with high expression of SLC20A1 and low expression of ALDH1A3 (SLC20A1highALDH1A3low), low expression of SLC20A1 and high expression of ALDH1A3 (SLC20A1lowALDH1A3high) and SLC20A1lowALDH1A3low. SLC20A1 siRNA KD in ALDH1high cells isolated from PANC-1 and MIA-PaCa-2 cell lines resulted in suppression of in vitro tumorsphere formation, and enhancement of cell death and caspase-3 activity. These results suggested that SLC20A1 was involved in cell survival via the suppression of caspase-3-dependent apoptosis, and contributed to cancer progression and poor clinical outcomes in PDAC. In conclusion, SLC20A1 may be used as a prognostic marker and novel therapeutic target of ALDH1-positive pancreatic CSCs. [ABSTRACT FROM AUTHOR]

Purpose: Docetaxel (DTX) is a standard chemotherapeutic drug for castration-resistant prostate cancer (CRPC), although adverse events are common. To overcome this problem, researchers have evaluated the efficacy of DTX treatment in combination with other drugs. Naftopidil is a tubulin-binding drug with fewer adverse events, implying the usefulness of this drug in clinical applications when combined with DTX. Here, we investigated the efficacy of additive naftopidil treatment in combination with DTX on prostate cancer (PCa) cells. Methods: The effects of combination treatment with DTX plus naftopidil were analyzed using two animal models of LNCaP cells plus PrSC xenografts (sub-renal capsule grafting) and PC-3 xenografts (intratibial injection). Results: Combination treatment with DTX plus naftopidil significantly inhibited cell growth in LNCaP cells compared with DTX alone. Analysis of the cooperativity index (CI) showed that combination treatment exhibited additive effects on DTX-induced growth inhibition in LNCaP cells. In contrast, combination treatment showed more than an additive (synergistic) effect on DTX-induced apoptosis in LNCaP and PC-3 cells. In LNCaP cells plus PrSC xenografts, combination treatment showed synergistic effects on DTX-induced apoptosis. The synergistic effects of naftopidil on DTX-induced apoptosis were also observed in PC-3 xenografts. Conclusions: Our results demonstrated that additive naftopidil treatment in combination with DTX increased the efficacy of DTX for the treatment of LNCaP and PC-3 tumors in vivo. Thus, additive naftopidil treatment showed a synergistic effect on DTX-induced apoptosis in PCa cells in vitro and in vivo, suggesting that this treatment approach may yield improved clinical benefits compared with DTX alone. [ABSTRACT FROM AUTHOR]