Identification of potential biomarkers for diagnosis of pancreatic and biliary tract cancers by sequencing of serum microRNAs

Background Pancreatic and biliary tract cancer (PC and BTC, respectively) are difficult to diagnose because of their clinical characteristics; however, recent studies suggest that serum microRNAs (miRNAs) might be the key to developing more efficient diagnostic methods for these cancers. Methods We analysed the genome-wide expression of serum miRNAs in PC and BTC patients to identify novel biomarker candidates using high-throughput sequencing and experimentally validated miRNAs on clinical samples. Results Statistical and classification analysis of the serum miRNA-expression profiles of 55 patient samples showed distinguishable patterns between cancer patients and healthy controls; however, we were unable to distinguish the two cancers. We found that three of the highest performing miRNAs were capable of distinguishing cancer patients from controls, with an accuracy of 92.7%. Additionally, dysregulation of these three cancer-specific miRNAs was demonstrated in an independent sample group by quantitative reverse transcription polymerase chain reaction. Conclusions These results suggested three candidate serum miRNAs (mir-744-5p, mir-409-3p, and mir-128-3p) as potential biomarkers for PC and BTC diagnosis.This work was supported by the Post-Genome Technology Development Program. (No. 10040174; Multiple biomarker development through validation of useful markers generated by next-generation bio-data-based genome research) funded by the Ministry of Trade, Industry, and Energy (MOTIE, Korea). The funders had no role in study design, data collection, analysis and interpretation of data, or in the writing of the manuscript

Laboratory information management system for COVID-19 non-clinical efficacy trial data

Background : As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results : In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions : This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.This research was supported by the National research foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2020M3A9I2109027 and 2021M3H9A1030260)

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Fig 3 -

The effects of a ketogenic diet (KD) on (a) gastrocnemius (GA) muscle morphology, (b) cross-sectional areas (CSA) and (c) Minimal Feret’s Diameter of GA muscle fiber, and (d) distribution of CSA of GA muscle fiber. (a) Representative photographs of hematoxylin and eosin (H&E)-stained GA muscle sections. Original magnification, 400x. Scale bar, 50 μm. Data are expressed as means ± SEM (n = 4 per group). One-way analysis of variance with Bonferroni post-hoc analysis was used to compare the differences in outcome variables between groups. * p † p < 0.05 vs. DM group. CON, control; DM, diabetes.</p

Fig 2 -

The effects of a ketogenic diet (KD) on serum concentrations of (a) corticosterone, (b) free fatty acids, (c) albumin, (d) insulin-like growth factor-1 (IGF-1), and (e) C-peptide, and pyruvate dehydrogenase (PDH) activity and acetyl-CoA concentration in gastrocnemius (GA) muscles. Data are expressed as means ± SEM (n = 10 per group). One-way analysis of variance with Bonferroni post-hoc analysis was used to compare the differences in outcome variables between groups. * p † p < 0.05 vs. DM group. CON, control; DM, diabetes.</p

The effects of a ketogenic diet (KD) on fasting serum glucose, the area under the curve (AUC) of oral glucose tolerance test (OGTT), fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and serum beta-hydroxybutyrate (BHB) concentrations in diabetic mice.

The effects of a ketogenic diet (KD) on fasting serum glucose, the area under the curve (AUC) of oral glucose tolerance test (OGTT), fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and serum beta-hydroxybutyrate (BHB) concentrations in diabetic mice.</p

Body weight (BW) changes, food intake, and muscle tissue weights in the ketogenic diet (KD)-fed mice.

Body weight (BW) changes, food intake, and muscle tissue weights in the ketogenic diet (KD)-fed mice.</p

Primer sequences for real-time reverse transcription polymerase chain reaction.

Primer sequences for real-time reverse transcription polymerase chain reaction.</p

Diagram of experimental procedure.

The mice of a ketogenic diet (KD) group were fed a KD from experimental week 8 for 6 weeks. CON, control; DM, diabetes melitus; NAM, nicotinamide; STZ, streptozotocin.</p

Diet composition.

Diabetes is often associated with reduced muscle mass and function. The ketogenic diet (KD) may improve muscle mass and function via the induction of nutritional ketosis. To test whether the KD is able to preserve muscle mass and strength in a mouse model of type 2 diabetes (T2DM), C57BL/6J mice were assigned to lean control, diabetes control, and KD groups. The mice were fed a standard diet (10% kcal from fat) or a high-fat diet (HFD) (60% kcal from fat). The diabetic condition was induced by a single injection of streptozotocin (STZ; 100 mg/kg) and nicotinamide (NAM; 120 mg/kg) into HFD-fed mice. After 8-week HFD feeding, the KD (90% kcal from fat) was fed to the KD group for the following 6 weeks. After the 14-week experimental period, an oral glucose tolerance test and grip strength test were conducted. Type 2 diabetic condition induced by HFD feeding and STZ/NAM injection resulted in reduced muscle mass and grip strength, and smaller muscle fiber areas. The KD nutritional intervention improved these effects. Additionally, the KD altered the gene expression of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome- and endoplasmic reticulum (ER) stress-related markers in the muscles of diabetic mice. Collectively, KD improved muscle mass and function with alterations in NLRP3 inflammasome and ER stress.</div