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In addition, genes involved in the PPI network were significantly enriched in the purine nucleoside monophosphate biosynthetic process, urate transport and biological processes associated with glycose metabolism. Collectively, to the best of our knowledge, the present study was the first to use WES to identify three candidate rare or novel deleterious mutations in three families with gout. The present results provided novel insights that may improve the current understanding of the molecular genetic basis underlying gout. Importantly, the present results may facilitate the improvement of clinical diagnosis and the development of novel personalized therapies.Tumor necrosis factor‑associated apoptosis‑inducing ligand (TRAIL) is considered to be a potential therapeutic target for various types of cancer. However, colon cancer is difficult to treat due to its resistance to TRAIL. Therefore, various trials have been conducted to overcome TRAIL resistance in colon cancer. The present study aimed to determine whether icariin (ICA) may sensitize human colon cancer cells to TRAIL‑induced apoptosis in vitro and in vivo. In the investigation of the effect of ICA on TRAIL‑induced apoptosis, the LIVE/DEAD assay results demonstrated that TRAIL plus ICA synergistically induced apoptosis in 49% of HCT116 colon cancer cells. These results were confirmed using long‑term colony formation assay. ICA potentiated TRAIL‑induced apoptosis by modulating the expression of apoptotic proteins and the induction of cell surface death receptors (DRs) 4 and 5. Upregulation of DRs by ICA was also observed at the transcriptional level by RT‑PCR. The expression of DR by ICA was increased through the production of reactive oxygen species (ROS). The results also suggested that increased expression of DR by ICA may be due to the activation of ERK and induction of the transcription factor CCAAT enhancer‑binding protein homologous protein (CHOP). NAC, a ROS scavenger, reduced the effect of ICA on ERK activation, DR induction and sensitization of TRAIL‑induced apoptosis. In addition, ICA enhanced the effects of TRAIL to reduce tumor growth in an in vivo xenograft mouse model. Overall, the present study provided evidence that ICA sensitized tumor cells to TRAIL‑induced apoptosis via ROS‑, ERK‑ and CHOP‑mediated upregulation of DR5 and DR4. Based on these results, it is suggested that the antitumor activity of ICA and TRAIL co‑treatment in vitro and in vivo may be used as an effective therapeutic agent in chemotherapy.Carbon monoxide‑releasing molecule‑3 (CORM‑3), which is an exogenous carbon monoxide (CO) compound, slowly releases CO under physiological conditions; this exerts neuroprotective effects against incomplete ischemia/reperfusion injury. The objective of the present study was to investigate whether the administration of CORM‑3 protects against nucleotide‑binding oligomerization domain‑like receptor pyrin domain‑3 (NLRP3) inflammasome formation and neuronal pyroptosis in the hippocampus following hemorrhagic shock and resuscitation (HSR). To establish this, an HSR model was created. Hemorrhagic shock was induced in adult male Sprague‑Dawley rats under sevoflurane anesthesia by bleeding using a heparinized syringe to maintain a mean arterial pressure of 30±5 mmHg for 60 min. Resuscitation was performed by reperfusion of the blood and, if necessary, administering sterile saline to achieve the baseline arterial pressure. Following resuscitation, CORM‑3 (4 mg/kg) was injected via the femoral vein. Neuronal pyroptosis in the hippocampus, mitochondrial morphology, mitochondrial DNA (mtDNA), brain magnetic resonance imaging, expression levels of NLRP3 and the interaction of pro‑caspase‑1 and apoptosis‑associated speck‑like protein containing a CARD domain (ASC) were examined 12 h after HSR; locomotor activity was assessed 7 days after HSR. Compared with HSR‑treated rats, CORM‑3 administration resulted in a lower level of neuronal pyroptosis in the hippocampus, improved mitochondrial morphology, a lower mtDNA level, steadier levels of metabolites, decreased expression levels of NLRP3 and pro‑caspase‑1 interacting with ASC and enhanced locomotor activity. In conclusion, treatment with CORM‑3 ameliorated impairments of locomotor and exploratory activities in a rat model of HSR. The mechanism may be associated with the inhibition of mitochondrial DNA‑induced pyroptosis via improvements in cell metabolism.Cofilin is associated with cell differentiation; however, to the best of our knowledge, no data have indicated an association between the cofilin 1 pathway and leukemia cell differentiation. The present study investigated the involvement of the cofilin 1 signaling pathway in diallyl disulfide (DADS)‑induced differentiation and the inhibitory effects on the proliferation, migration, and invasion of human leukemia HL‑60 cells. First, it was identified that 8 µM DADS suppressed cell proliferation, migration and invasion, and induced differentiation based on the reduced nitroblue tetrazolium ability and increased CD11b and CD33 expression. DADS significantly downregulated the expression of cofilin 1 and phosphorylated cofilin 1 in HL‑60 leukemia cells. Second, it was verified that silencing cofilin 1 markedly promoted 8 µM DADS‑induced differentiation and the inhibitory effect on cell proliferation and invasion. Overexpression of cofilin 1 obviously suppressed 8 µM DADS‑induced differentiation and the inhibitory effect on cell proliferation and invasion. Third, the present study examined the mechanisms by which 8 µM DADS decreases cofilin 1 expression and activation. The results revealed that 8 µM DADS inhibited the mRNA and protein expression of Rac1, Rho‑associated protein kinase 1 (ROCK1) and LIM domain kinase 1 (LIMK1) as well as the phosphorylation of LIMK1 in HL‑60 cells, while 8 µM DADS enhanced the effects of the Rac1‑ROCK1‑LIMK1 pathway in cells overexpressing cofilin 1 compared with that in control HL‑60 cells. These results suggest that the anticancer function of DADS on HL‑60 leukemia cells is regulated by the Rac1‑ROCK1‑LIMK1‑cofilin 1 pathway, indicating that DADS could be a promising anti‑leukemia therapeutic compound.Scutellarein has been identified to serve an anti‑tumor function in human colon cancer, but the underlying mechanisms remain largely unclear. The present study further investigated the effect and mechanism of scutellarein, extracted from wild chrysanthemum, in the progression of colon cancer. MTT, clone formation, flow cytometry and tumor‑bearing mice assays were used to detect cell viability, clone formation, apoptosis and tumorigenesis, respectively. Western blot and quantitative PCR assays were performed for protein and mRNA expression detection. The results revealed that, compared with the control group, scutellarein treatment significantly inhibited the viability and induced the apoptosis of colon cancer cells (P less then 0.05), with significant decreases in receptor for advanced glycosylation end products (RAGE) protein expression and stability and an increase in RAGE ubiquitination (P less then 0.05). However, the effects of scutellarein exerted in cell apoptosis and viability were rescued by RAGE overexpression, and accelerated by RAGE knockdown. Additionally, it was observed that scutellarein treatment induced a significant increase in the expression of cell division control protein 4 (CDC4) compared with the control group (P less then 0.05), which was then verified to interact with RAGE protein and mediate its ubiquitination. Overexpression of CDC4 inhibited colon cancer cell viability and promoted the apoptosis of SW480 and T84 cells, whereas this function was weakened when RAGE was overexpressed. Furthermore, CDC4 downregulation significantly neutralized scutellarein functions in promoting cell apoptosis and inhibiting cell viability and tumorigenesis in colon cancer cells compared with the scutellarein group (P less then 0.05). In conclusion, the present study revealed that scutellarein inhibited the development of colon cancer through upregulating CDC4‑mediated RAGE ubiquitination.Pancreatic cancer is a lethal solid malignancy with limited therapeutic options. https://www.selleckchem.com/products/gw3965.html The development of novel therapeutic drugs requires adequate new cell line models. A new pancreatic cancer cell line, designated PDXPC1, was established from one pancreatic ductal adenocarcinoma (PDAC) patient‑derived xenograft. The PDXPC1 cells were stably cultured for >2 years and had a stable short tandem repeat profile. The PDXPC1 cell line retained the key mutations of the primary tumor, along with the epithelial origin and other important protein expression. The PDXPC1 cells induced rapid in vivo tumor growth, both subcutaneously and orthotopically, in a mouse model with an elevated CA199 level. The PDXPC1 cells showed weak growth, invasion and migration potency compared to another pancreatic cancer cell line, but were relatively resistant to multiple anti‑cancer drugs. Interestingly, the MEK inhibitor trametinib significantly inhibited the proliferation of PDXPC1 cells, and not that of Panc‑1 cells, by inactivating MEK/ERK/MYC signaling and activating the apoptotic pathway via Bcl‑2 degradation. In conclusion, the PDXPC1 cell line, capturing the major characteristics of the primary tumor, may be a suitable tool for studying the underlying mechanisms of chemo‑resistance in PDAC and developing new targeted therapeutic options.Drug repositioning refers to the concept of discovering novel clinical benefits of drugs that are already known for use treating other diseases. The advantages of this are that several important drug characteristics are already established (including efficacy, pharmacokinetics, pharmacodynamics and toxicity), making the process of research for a putative drug quicker and less costly. Drug repositioning in oncology has received extensive focus. The present review summarizes the most prominent examples of drug repositioning for the treatment of cancer, taking into consideration their primary use, proposed anticancer mechanisms and current development status.Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for ~10% of all newly diagnosed leukemia cases. Early diagnosis is essential for long‑term beneficial outcomes. The present study observed that interferon‑induced protein with tetratricopeptde repeats 2 (IFIT2) expression levels were reduced in bone marrow samples from CML patients compared with control samples using RNA sequencing and reverse transcription‑PCR. IFIT2 expression levels were restored in patients treated with tyrosine kinase inhibitors. To investigate the effect of IFIT2 on CML patients, a stable IFIT2 expressing K562 cell line was established. It was demonstrated that IFIT2 overexpression in K562 cells inhibits cell proliferation and arrests the cell cycle at the G1 phase. In addition, it was demonstrated by western blotting that IFIT2 inhibits the BCR‑ABL oncoprotein and regulates its downstream AKT/mTOR signaling pathway. IFIT2 could induce cell cycle arrest‑associated gene p27kip1 by degrading cullin1‑mediated E3 ligases.