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Recent studies have reported that the expression levels of far upstream element‑binding protein 1 (FUBP1) were upregulated and served a crucial role in several types of cancer. However, the underlying molecular mechanisms and clinical significance of FUBP1 in pancreatic adenocarcinoma (PAAD) remain unclear. The present study aimed to determine the expression levels of FUBP1 in patients with PAAD and subsequently investigated the biological functions and mechanisms of FUBP1 using in vitro assays. FUBP1 expression levels and survival outcomes in patients with PAAD were analyzed using The Cancer Genome Atlas and starBase databases. Reverse transcription‑quantitative PCR was used to analyze the mRNA expression levels of FUBP1 in PAAD and adjacent normal tissues. In addition, the expression of FUBP1 was knocked down with small interfering RNA and overexpressed using FUBP1‑overexpressed plasmids, and the effects on biological functions, including cell proliferation, migration and invasion, were investigated. Western blotting and immunofluorescence assays were used to determine the role of FUBP1 in epithelial‑mesenchymal transition (EMT). The results of the present study revealed that the expression levels of FUBP1 were upregulated in PAAD tissues compared with adjacent normal tissues and the upregulated expression was significantly associated with poor survival. The knockdown of FUBP1 expression significantly inhibited the proliferative, migratory and invasive abilities of the PAAD PaTu8988 cell line, while the overexpression of FUBP1 promoted cell proliferation, migration and invasion in the PAAD SW1990 cell line. Furthermore, the knockdown of FUBP1 downregulated the expression levels of EMT‑related markers, including N‑cadherin, β‑catenin and vimentin, while the expression levels of E‑cadherin were upregulated. The knockdown of FUBP1 was also revealed to regulate the TGFβ/Smad signaling cascade by downregulating phosphorylated‑Smad2/3 and TGFβ1 expression levels. Conversely, the overexpression of FUBP1 reversed these effects. In conclusion, the findings of the present study indicated that FUBP1 may be a potential oncogene that mediates the EMT of PAAD via TGFβ/Smad signaling. These data suggested that FUBP1 may represent a potential biomarker for the diagnosis of PAAD or a target for the treatment of patients with PAAD.

Coal and methane were mixed and burned in the moderate and intensive low oxygen dilution–oxy coal combustion (MILD–OCC) mode, flame temperature was measured at different flame locations wit...

Background Brain glucose hypometabolism is an invariant feature and has significant diagnostic value for Alzheimer's disease. Thiamine diphosphate (TDP) is a critical coenzyme for glucose metabolism and significantly reduced in brain and blood samples of patients with Alzheimer's disease (AD). Aims To explore the diagnostic value of the measurement of blood thiamine metabolites for AD. Methods Blood TDP, thiamine monophosphate, and thiamine levels were detected using high performance liquid chromatography (HPLC). The study included the exploration and validation phases. In the exploration phase, the samples of 338 control subjects and 43 AD patients were utilized to establish the models for AD diagnosis assayed by receiver operating characteristic (ROC) curve, including the variable γ that represents the best combination of thiamine metabolites and age to predict the possibility of AD. In the validation phase, the values of models were further tested for AD diagnosis using samples of 861 control subjects, 81 AD patients, 70 vascular dementia patients, and 13 frontotemporal dementia patients. Results TDP and the γ exhibited significant and consistent values for AD diagnosis in both exploration and validation phases. TDP had 0.843 and 0.837 of the areas under ROC curve (AUCs), 77.4% and 81.5% of sensitivities, and 78.1% and 77.2% of specificities respectively in the exploration and validation phases. The γ had 0.938 and 0.910 of AUCs, 81.4% and 80.2% of sensitivities, and 90.5% and 87.2% of specificities respectively in the exploration and validation phases. TDP and the γ can effectively distinguish AD from vascular dementia (64.3% for TDP, 67.1% for γ) and frontotemporal dementia (84.6% for TDP, 100.0% for γ). Interpretation. The measurement of blood thiamine metabolites by HPLC is an ideal diagnostic test for AD with inexpensive, easy to perform, noninvasive merits., Highlights • The measurement of blood thiamine metabolites by HPLC as a promising biomarker test for Alzheimer’s disease diagnosis. • This test is inexpensive, easy to perform and noninvasive which meets the criteria of ideal biomarker for Alzheimer’s disease. The disturbance of brain glucose metabolism is an invariant feature and has significant diagnostic value for Alzheimer's disease. Thiamine diphosphate, one of thiamine metabolites, is a critical coenzyme for three key enzymes of glucose metabolism and significantly reduced in brain and blood samples of a small number of Alzheimer's disease patients. Our study demonstrates that the measurement of blood thiamine metabolites, manifested as thiamine diphosphate level and the variable γ representing the best combination of thiamine metabolites and age, exhibits excellent value for Alzheimer's disease diagnosis with inexpensive, easy to perform, noninvasive merits.

Thiamine metabolism is critical for glucose metabolism and also vital for brain function, which is susceptible to decline in the elderly. This study aimed to investigate whether thiamine metabolites correlate with cognitive function in the non-demented elderly and their impact factors. Volunteers >60 years old were recruited and their blood thiamine metabolites and Mini-Mental State Examination (MMSE) scores were measured. The apolipoprotein E (APOE) genotype, routine blood parameters, liver and kidney function, and levels of fasting blood glucose and triglycerides were also measured. The results showed that the thiamine diphosphate (TDP) level weakly correlated with MMSE score in the non-demented elderly. Participants with high TDP levels performed better in Recall and Attention and Calculation than those with low TDP. TDP levels were associated with the APOE e2 allele, body mass index, hemoglobin level, fasting blood glucose, and triglycerides. Our results suggest that TDP, which is easily affected by many factors, impacts cognitive function in the elderly.