Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice

With the increasing use of immune-checkpoint inhibitors (ICIs), such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death-1 (PD-1), for the treatment of malignancies, cases of ICI-induced type 1 diabetes mellitus (ICI-T1DM) have been reported globally. This review focuses on the features and pathogenesis of this disease. T1DM is an immune-related adverse event that occurs following the administration of anti-PD-1 or anti-programmed death ligand-1 (PD-L1) alone or in combination with anti-CTLA-4. More than half of the reported cases presented as abrupt-onset diabetic ketoacidosis. The primary mechanism of ICI-T1DM is T-cell stimulation, which results from the loss of interaction between PD-1 and PD-L1 in pancreatic islet. The similarities and differences between ICI-T1DM and classical T1DM may provide insights into this disease entity. ICI-T1DM is a rare but often life-threatening medical emergency that healthcare professionals and patients need to be aware of. Early detection of and screening for this disease is imperative. At present, the only known treatment for ICI-T1DM is insulin injection. Further research into the mechanisms and risk factors associated with ICI-T1DM development may contribute to a better understanding of this disease entity and the identification of possible preventive strategies

Staphylococcal enterotoxin sensitization in a community-based population : a potential role in adult-onset asthma

Background: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. Objective: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. Methods: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age=60.2years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. Results: Staphylococcal enterotoxin sensitization (0.35kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (61years), and inhalant allergen sensitization. Current asthma was mostly adult onset (18years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. Conclusions and Clinical Relevance: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis

Simultaneous VLBI Astrometry of H2O and SiO Masers toward the Semiregular Variable R Crateris

We obtained, for the first time, astrometrically registered maps of the 22.2 GHz H2O and 42.8, 43.1, and 86.2 GHz SiO maser emission toward the semiregular b-type variable (SRb) R Crateris, at three epochs (2015 May 21, and 2016 January 7 and 26) using the Korean Very-long-baseline Interferometry Network. The SiO masers show a ring-like spatial structure, while the H2O maser shows a very asymmetric one-side outflow structure, which is located at the southern part of the ring-like SiO maser feature. We also found that the 86.2 GHz SiO maser spots are distributed in an inner region, compared to those of the 43.1 GHz SiO maser, which is different from all previously known distributions of the 86.2 GHz SiO masers in variable stars. The different distribution of the 86.2 GHz SiO maser seems to be related to the complex dynamics caused by the overtone pulsation mode of the SRb R Crateris. Furthermore, we estimated the position of the central star based on the ring fitting of the SiO masers, which is essential for interpreting the morphology and kinematics of a circumstellar envelope. The estimated stellar coordinate corresponds well to the position measured by Gaia

Effects of Berberine and Hwangryunhaedok-Tang on Oral Bioavailability and Pharmacokinetics of Ciprofloxacin in Rats

Hwangryunhaedok-Tang (HR) and berberine-containing single herbs are used to treat bacterial infection and inflammatory diseases in eastern Asia. The combination of berberine-containing herbal medicines and ciprofloxacin can be an excellent antibacterial chemotherapy against multidrug resistance bacteria. To evaluate the pretreatment effect of berberine and HR, vehicle, berberine (25 and 50 mg/kg/day), and HR (1.4 g/kg/day) were daily administered to rats for five consecutive days. On day 6, ciprofloxacin was administered (10 mg/kg, i.v. and 20 mg/kg, p.o.) to rats. To assess cotreatment effect of berberine and ciprofloxacin, berberine (50 mg/kg) and ciprofloxacin (20 mg/kg) were coadministered by single oral gavage. Pharmacokinetic data were estimated by noncompartmental model. Compared with ciprofloxacin alone (control group), coadministration of berberine (50 mg/kg) and ciprofloxacin significantly decreased Cmax of ciprofloxacin (P<0.05). In addition, the pretreatment of berberine (50 mg/kg/day) and HR (1.4 g/kg/day) significantly decreased Cmax and AUC0→∞, compared with control group (P<0.05). The oral bioavailability of ciprofloxacin was reduced by cotreatment of berberine and pretreatment of berberine and HR. Our results suggest that the expression of P-glycoprotein and organic anion and/or organic cation transporters (OAT/OCT) could take a role in reduced oral bioavailability of ciprofloxacin by berberine and HR

Pancreatic serous cystadenocarcinoma with invasive growth into the colon and spleen

Serous cystic neoplasms of the pancreas are almost always benign lesions. However, there are some case reports of malignant serous neoplasms of the pancreas. It is very difficult to distinguish malignant and benign tumors. Indeed, only clinicopathologic findings of locoregional invasion and metastasis represent a malignancy. We report a serous cystadenocarcinoma of the pancreas that was initially considered to be colon cancer. Post-operatively, the tumor was confirmed to be a malignant serous cystic tumor of the pancreas. One year later, the patient remains disease-free

Precise stacking of decellularized extracellular matrix based 3D cell-laden constructs by a 3D cell printing system equipped with heating modules

Three-dimensional (3D) cell printing systems allow the controlled and precise deposition of multiple cells in 3D constructs. Hydrogel materials have been used extensively as printable bioinks owing to their ability to safely encapsulate living cells. However, hydrogel-based bioinks have drawbacks for cell printing, e.g. inappropriate crosslinking and liquid-like rheological properties, which hinder precise 3D shaping. Therefore, in this study, we investigated the influence of various factors (e.g. bioink concentration, viscosity, and extent of crosslinking) on cell printing and established a new 3D cell printing system equipped with heating modules for the precise stacking of decellularized extracellular matrix (dECM)-based 3D cell-laden constructs. Because the pH-adjusted bioink isolated from native tissue is safely gelled at 37 degrees C, our heating system facilitated the precise stacking of dECM bioinks by enabling simultaneous gelation during printing. We observed greater printability compared with that of a non-heating system. These results were confirmed by mechanical testing and 3D construct stacking analyses. We also confirmed that our heating system did not elicit negative effects, such as cell death, in the printed cells. Conclusively, these results hold promise for the application of 3D bioprinting to tissue engineering and drug development.119Ysciescopu