Identification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants.

We identified neutralizing monoclonal antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants (including Omicron variants BA.5 and BA.2.75) from individuals who received two doses of mRNA vaccination after they had been infected with the D614G virus. We named them MO1, MO2, and MO3. Among them, MO1 showed particularly high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, BA.2.75, and BA.5. Furthermore, MO1 suppressed BA.5 infection in hamsters. A structural analysis revealed that MO1 binds to the conserved epitope of seven variants, including Omicron variants BA.5 and BA.2.75, in the receptor-binding domain of the spike protein. MO1 targets an epitope conserved among Omicron variants BA.1, BA.2, and BA.5 in a unique binding mode. Our findings confirm that D614G-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants. IMPORTANCE Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages. It was speculated that the patients have neutralizing antibodies broadly effective against SARS-CoV-2 variants by targeting common epitopes. Here, we explored human monoclonal antibodies from B cells of the patients. One of the monoclonal antibodies, named MO1, showed high potency against broad SARS-CoV-2 variants including BA.2.75 and BA.5 variants. The results prove that monoclonal antibodies that have common neutralizing epitopes among several Omicrons were produced in patients infected with D614G and who received mRNA vaccination.

Photochemical OFF/ON Cytotoxicity Switching by Using a Photochromic Surfactant with Visible Light Irradiation.

Photochemical switching of cytotoxicity by using spiropyran compounds with pyridinium and alkyl groups was investigated. The spiropyran compound, SP6, with a hexyl group as the alkyl group displayed negative photochromism, in which the hydrophilic open merocyanine form (MC form) was stable and isomerized to the hydrophobic closed spiro form (SP form) by visible light irradiation. Both MC and SP forms exhibited amphiphilicity because of the hydrophobic hexyl and hydrophilic pyridinium groups introduced. Cytotoxicity toward HeLa cells was observed for both MC and SP forms of SP6 at concentrations higher than the critical aggregation concentration of the isomers CACMC and CACSP (CACMC > CACSP), respectively. In contrast, cytotoxicity by SP6 was activated by visible light irradiation at concentrations between CACMC and CACSP; thus, photochemical switching of cytotoxicity from the OFF to ON state was achieved. Cytotoxicity was revealed to be caused by disruption of the cell membrane. The results provide an important step in developing novel next-generation photochemotherapy drugs.

Analysis of the Effects of Food Additives on Porphyromonas gingivalis.

This study aims to investigate six food additives (octanoic acid, decanoic acid, acesulfame K, aspartame, saccharin, and sucralose) used in foods for the elderly or people with dysphagia because of the effect of these food additives on Porphyromonas gingivalis (P. gingivalis), which is a keystone pathogen of periodontal diseases. The growth of P. gingivalis was inhibited by 5 mM octanoic acid, 1.25 mM decanoic acid, 1.25% acesulfame K, 0.0625% aspartame, 0.03125% saccharin, and 0.625% sucralose. In addition, these food additives showed bactericidal activity for planktonic P. gingivalis (5 mM octanoic acid, 5 mM decanoic acid, 0.25% aspartame, 0.25% saccharin, and 5% sucralose). Moreover, biofilm formation was inhibited by 10 mM octanoic acid, 10 mM decanoic acid, 10% acesulfame K, 0.35% aspartame, 0.5% saccharin, and 7.5% sucralose. Moreover, the same concentration of these food additives without aspartame killed P. gingivalis in the biofilm. Aspartame and sucralose did not show cytotoxicity to human cell lines at concentrations that affected P. gingivalis. These findings may be useful in clarifying the effects of food additives on periodontopathogenic bacteria.

Effect of real-life insulin pump with predictive low-glucose management use for 3 months: Analysis of the patients treated in a Japanese center.

AIMS/INTRODUCTION: In Japan, an insulin pump with predictive low-glucose management (PLGM) was launched in 2018. It automatically suspends insulin delivery when the sensor detects or predicts low glucose values. The aim of this study was to analyze the safety and efficacy of PLGM in patients treated in a Japanese center. MATERIALS AND METHODS: We carried out a retrospective observational analysis of 16 patients with type 1 diabetes mellitus and one patient after pancreatectomy. They switched from the MiniMed 620G device to the 640G device with PLGM. The primary outcome was the change in the percentage of time in hypoglycemia. The secondary outcome was the change in HbA1c (%) over a period of 3 months. We also explored the presence of "post-suspend hyperglycemia" with the 640G device. RESULTS: After changing to the 640G device, the percentage of time in hypoglycemia (glucose <50 mg/dL) significantly decreased from 0.39% (0-1.51%) to 0% (0-0.44%; P = 0.0407). The percentage of time in hyperglycemia (glucose >180 mg/dL) significantly increased from 25.53% (15.78-44.14%) to 32.9% (24.71-45.49%; P = 0.0373). HbA1c significantly increased from 7.6 ± 1.0% to 7.8 ± 1.1% (P = 0.0161). From 1.5 to 4.5 h after the resumption of insulin delivery, the percentage of time in hyperglycemia was 32.23% (24.2-53.75%), but it was significantly lower, 2.78% (0-21.6%), when patients manually restarted the pump within 30 min compared with automatic resumption 31.2% (20-61.66%; P = 0.0063). CONCLUSIONS: Predictive low-glucose management is an effective tool for reducing hypoglycemia, but possibly elicits "post-suspend hyperglycemia." This information is useful for achieving better blood glucose control in the patients treated with PLGM.

Effect of Plasma Exchange in Thyroid Storm With Consideration of Its Distribution Into the Extravascular Space.

Plasma exchange (PE), which directly removes some plasma thyroid hormones, is a treatment option for thyroid storm. However, the effect of PE has not been accurately assessed yet. Here we assessed the effect of PE in a patient with thyroid storm while taking into consideration the distribution of thyroid hormones in the extravascular space. A 51-year-old woman with thyroid storm underwent 2 PE procedures at our hospital. By measuring changes in thyroid hormone levels in plasma, fresh frozen plasma (FFP) used, and waste fluid during each 2.5-hour PE procedure, we calculated the efficiency of thyroid hormone removal based on the hypothesis that total thyroid hormone content before and after PE is the same. During the patient's first PE procedure, the estimated thyroxine (T4) balance in the extravascular space (ΔX) was -70 µg, which corresponds to approximately 19% of T4 in the waste fluid. During the second PE procedure, ΔX was -131 µg, which corresponds to approximately 52% of T4 in the waste fluid. These data indicated that the source of removed T4 during PE varies. The amount of T4 removed from the extravascular space should be taken into account during assessment of the effect of PE in thyroid storm.

Postprandial Plasma Glucagon Kinetics in Type 2 Diabetes Mellitus: Comparison of Immunoassay and Mass Spectrometry.

CONTEXT: Accurate glucagon level measurements are necessary for investigation of mechanisms for postprandial hyperglycemia in type 2 diabetes. OBJECTIVE: To evaluate the accuracy of postprandial glucagon level measurements using a sandwich ELISA vs a recently established liquid chromatography-high resolution mass spectrometry (LC-HRMS) method in type 2 diabetes mellitus. DESIGN AND PARTICIPANTS: Twenty patients with type 2 diabetes treated with insulin underwent a meal test before and after administration of the dipeptidyl peptidase-4 inhibitor anagliptin for 4 weeks. Blood samples were taken serially after the meal, and glucagon levels were measured using both ELISA and LC-HRMS. We compared the change from baseline to 4 weeks (Δ0-4W) using the area under the curve for plasma glucagon during the meal test [area under the curve (AUC)0-3h] measured using ELISA and LC-HRMS. RESULTS: ELISA-based glucagon AUC0-3h was higher than LC-HRMS-based AUC0-3h at baseline and 4 weeks. However, differences in Δ0-4W-AUC0-3h measured using ELISA and LC-HRMS were not statistically significant. Additionally, Δ0-4W-AUC0-3h measured using ELISA and LC-HRMS were strongly correlated (r = 0.87, P < 0.001). CONCLUSIONS: Plasma glucagon levels during a meal test in patients with type 2 diabetes measured using ELISA were consistently higher than those measured using LC-HRMS. However, given that the changes in glucagon levels measured using ELISA before and after dipeptidyl peptidase-4 inhibitor therapy were similar to those based on LC-HRMS, this ELISA seems to be useful for evaluating the effect of the drug interventions on postprandial glucagon levels.