Background: Obesity can lead to ectopic pancreatic fat accumulation and increase the risk for type 2 diabetes. Smaller intervention trials have shown a decrease in pancreatic fat content (PFC) with weight loss, and we intended to investigate the effects of weight loss on PFC in a larger trial. Methods: Data from the HELENA-Trial, a randomized controlled trial (RCT) among 137 non-diabetic obese adults were used. The study cohort was classified into 4 quartiles based on weight change between baseline and 12 weeks post-intervention. Changes in PFC (baseline, 12 weeks and 50 weeks post-intervention) upon weight loss were analyzed by linear mixed models. Spearman’s coefficients were used to obtain correlations between anthropometric parameters, blood biochemical markers, and PFC. Results: At baseline, PFC only showed a significant correlation with visceral adipose tissue (VAT) (r = 0.41). Relative changes in PFC were significantly (p = 0.01) greater in Q4 (−30.8 ± 5.7%) than in Q1 (1.3 ± 6.7%). These differences remained similar after one year. However, when adjusting the statistical analyses for changes in VAT, the differences in PFC between Q1 and Q4 were no longer statistically significant. Conclusion: Weight loss is associated with a decrease in PFC. However, the reduction of PFC is not independent from reductions in VAT. Unlike VAT, PFC was not associated with metabolic biomarkers.
RNA research and applications are underpinned by in vitro transcription (IVT), but RNA impurities resulting from the enzymatic reagents severely impede downstream applications. To improve the stability and purity of synthesized RNA, we have characterized a novel single-subunit RNA polymerase (RNAP) encoded by the psychrophilic phage VSW-3 from a plateau lake. The VSW-3 RNAP is capable of carrying out in vitro RNA synthesis at low temperatures (4–25°C). Compared to routinely used T7 RNAP, VSW-3 RNAP provides a similar yield of transcripts but is insensitive to class II transcription terminators and synthesizes RNA without redundant 3’-cis extensions. More importantly, through dot-blot detection with the J2 monoclonal antibody, we found that the RNA products synthesized by VSW-3 RNAP contained a much lower amount of double-stranded RNA byproducts (dsRNA), which are produced by transcription from both directions and are significant in T7 RNAP IVT products. Taken together, the VSW-3 RNAP almost eliminates both terminal loop-back dsRNA and full-length dsRNA in IVT and thus is especially advantageous for producing RNA for in vivo use.
Extensive desmoplastic stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor progression and to the relative resistance of tumor cells towards (radio) chemotherapy. Thus, therapies that target the stroma are under intense investigation. To allow the stratification of patients who would profit from such therapies, non-invasive methods assessing the stroma content in relation to tumor mass are required. In the current prospective study, we investigated the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI), a radiologic method that measures the random motion of water molecules in tissue, in the assessment of PDAC lesions, and more specifically in the desmoplastic tumor stroma. We made use of a sophisticated DW-MRI approach, the so-called diffusion kurtosis imaging (DKI), which possesses potential advantages over conventional and widely used monoexponential diffusion-weighted imaging analysis (cDWI). We found that the diffusion constant D from DKI is highly negatively correlated with the percentage of tumor stroma, the latter determined by histology. D performed significantly better than the widely used apparent diffusion coefficient (ADC) from cDWI in distinguishing stroma-rich (>50% stroma percentage) from stroma-poor tumors (≤50% stroma percentage). Moreover, we could prove the potential of the diffusion constant D as a clinically useful imaging parameter for the differentiation of PDAC-lesions from non-neoplastic pancreatic parenchyma. Therefore, the diffusion constant D from DKI could represent a valuable non-invasive imaging biomarker for assessment of stroma content in PDAC, which is applicable for the clinical diagnostic of PDAC.
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