The limited efficacy of current treatment methods and increased type 2 diabetes mellitus (T2DM) incidence constitute an incentive for investigating how metabolic homeostasis is maintained, to improve treatment efficacy and identify novel treatment methods. We analyzed a three-generation family of Chinese origin with the common feature of T2DM attacks and fatty pancreas (FP), alongside 19 unrelated patients with FP and 58 cases with T2DM for genetic variations in Enho, serum adropin, and relative T_reg amounts. Functional studies with adropin knockout (AdrKO) in C57BL/6J mice were also performed. It showed serum adropin levels were significantly lower in FP and T2DM patients than in healthy subjects; relative T_reg amounts were also significantly decreased in FP and T2DM patients, and positively associated with adropin (r=0.7220, P=0.0001). Sequencing revealed that the patients shared a Cys56Trp mutation in Enho. In vivo, adropin-deficiency was associated with increased severity of glucose homeostasis impairment and fat metabolism disorder. AdrKO mice exhibited reduced endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177), impaired glycosphingolipid biosynthesis, adipocytes infiltrating, and loss of T_reg, and developed FP and T2DM. Adropin-deficiency contributed to loss of T_reg and the development of FP disease and T2DM.

Background: Previous studies revealed somatic mutations of the cationic trypsinogen gene (PRSS1) in patients with chronic pancreatitis and pancreatic cancer. However, whether PRSS1 mutations trigger pancreatic cancer and/or promote malignant proliferation and metastasis in pancreatic cancer remains largely unclear, as well as the potential underlying mechanisms. Methods: In the present study, whole-exome sequencing was applied for screening, and the R116C mutation was validated by Sanger sequencing. Phosphorylation antibody array, RNA-Seq, and RT-qPCR were adopted to screen and validate that R116C mutation promoted pancreatic cancer progression via the JAK1-STAT5 pathway. Results: It showed that migration and invasion were significantly increased in R116C-bearing PANC-1 cells compared with wild type counterparts. In a transgenic mouse model of iZEG-PRSS1_R116C, primary pancreatic intraepithelial neoplasia (PanINs) was observed in the pancreatic duct. Conclusions: These findings suggested a novel pathway mediating pancreatic cancer development, with PRSS1 mutation and overexpression playing an “inside job” role in pancreatic carcinogenesis and tumor development.

Objective: To establish an electrochemical immunosensor for the determination of serum trypsin levels using a multiwall carbon nanotubes (MWCNTs)-composite-modified electrode. Method: A MWCNT composite coated on the surface of bare gold electrodes was used for fixation of an anti-trypsin antibody. The assembly process and the performance indicators, including sensitivity, linear range of detection, anti-jamming performance, and stability, of the electrochemical immunosensor were examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Results: With optimized experimental conditions, the difference of the current value measured by differential pulse voltammetry (DPV) showed a linear relationship with the concentration of serum trypsin within 0.10–100 ng/mL. The detection limit for trypsin using this sensor was 0.002 ng/mL. Conclusions: The electrochemical immunosensor built using the MWCNT-composite-modified electrode is simple to operate and has a fast response time, along with a wide linear range, high sensitivity, and accuracy, making it suitable for serum trypsin detection.

Concomitant exotropia have obvious symptoms of eye discomfort in adults, and the presence of ocular surface inflammation in patients may be important mediators between concomitant exotropia and dry eye. Oculus Keratograph eye comprehensive analyzer was performed to detect noninvasive tear break time, noninvasive tear height, and eye red index, while the ocular surface disease index and schirmer I testing were made. The levels of IL‐6, IL‐10, IL‐17A, IL‐12P70, INF‐γ, and TNF‐α were detected in tears in patients with concomitant exotropia and healthy controls matched by age and gender through the Simoa technology. IL‐6 was significantly higher in patients with concomitant exotropia (4.683 ± 1.329) pg/mL than that in normal group (1.455 ± 0.391) pg/mL, p = 0.0304. TNF‐α was also significantly higher in patients (0.2095 ± 0.0703) pg/mL than normal group (0.0513 ± 0.0149) pg/mL, p = 0.0397. The levels of inflammatory factors in strabismic patients vs. normal controls were as follows: IL‐17A (0.1551 pg/mL︰0.0793 pg/mL), IL‐10 (0.3358 pg/mL︰0.0513 pg/mL), IL‐12p70 (0.0253 pg/mL︰0.0099 pg/mL), and INF‐γ (0.0284 pg/mL︰0.009 pg/mL) were detected, and the median of them in concomitant strabismus was 1.96‐6.55‐fold as much as the control group. High levels of inflammatory cytokines in tears of patients with concomitant exotropia, which may be a potentially factor promoted the occurrence of dry eye in the patients with concomitant exotropia.

Stem cells have the ability of self‐replication and multidirectional differentiation, but the mechanism of how stem cells “maintain” this ability and how to “decide” to give up this state and differentiate into cells with specific functions is still unknown. The Nobel Prize in physiology and medicine in 2021 was awarded to “temperature and tactile receptor,” which made the pain receptor TRPV1‐calcitonin gene‐related peptide (CGRP) pathway active again. The activation and blocking technology of CGRP has been applied to many clinical diseases. CGRP gene has complex structure and transcription process, with multiple methylation and other modification sites. It has been considered as a research hotspot and difficulty since its discovery. Drug manipulation of TRPV1 and inhibition of CGRP might improve metabolism and prolong longevity. However, whether the TRPV1‐neuropeptide‐CGRP pathway is directly or indirectly involved in stem cell self‐replication and multidirectional differentiation is unclear. Recent studies have found that CGRP is closely related to the migration and differentiation of tumor stem cells, which may be realized by turning off or turning on the CGRP gene expression in stem cells and activating a variety of ways to regulate stem cell niches. In this study, we reviewed the advances in researches concentrated on the biological effects of CGRP as a new endogenous switching of cell stemness.

Recently, we have demonstrated that PRSS1 mutations cause ectopic trypsinogen activation and thereby result in type 1 autoimmune pancreatitis (AIP). However, the molecules involved in inducing obliterative vasculitis and perineural inflammation in the pancreas are not well-described. The present study applied whole-exome sequencing (WES) to determine the underlying etiology and revealed novel missense splice region variants, CALCB c.88T>C (p.Ser30Pro) and IR [1]-mutants, in 2 of the 3 families and 2 of 26 unrelated patients with type 1 AIP. In vitro, both of the mutants displayed decreased βCGRP, ERK1/2 phosphorylation, and co-localized with endoplasmic reticulum and Golgi apparatus. The novel pathogenic variant identified in this case should contribute to our understanding of the expanding spectrum of AIP.