-
1.
Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1.
Ozawa, T, Ikeda, Y, Chen, L, Suzuki, R, Hoshino, A, Noguchi, A, Kita, S, Anraku, Y, Igarashi, E, Saga, Y, et al
Structure (London, England : 1993). 2024;(3):263-272.e7
Abstract
SARS-CoV-2 rapidly mutates and acquires resistance to neutralizing antibodies. We report an in-silico-designed antibody that restores the neutralizing activity of a neutralizing antibody. Our previously generated antibody, UT28K, exhibited broad neutralizing activity against mutant variants; however, its efficacy against Omicron BA.1 was compromised by the mutation. Using previously determined structural information, we designed a modified-UT28K (VH T28R/N57D), UT28K-RD targeting the mutation site. In vitro and in vivo experiments demonstrated the efficacy of UT28K-RD in neutralizing Omicron BA.1. Although the experimentally determined structure partially differed from the predicted model, our study serves as a successful case of antibody design, wherein the predicted amino acid substitution enhanced the recognition of the previously elusive Omicron BA.1. We anticipate that numerous similar cases will be reported, showcasing the potential of this approach for improving protein-protein interactions. Our findings will contribute to the development of novel therapeutic strategies for highly mutable viruses, such as SARS-CoV-2.
-
2.
Effects of Food and Liquid Properties on Swallowing Physiology and Function in Adults.
Peña-Chávez, RE, Schaen-Heacock, NE, Hitchcock, ME, Kurosu, A, Suzuki, R, Hartel, RW, Ciucci, MR, Rogus-Pulia, NM
Dysphagia. 2023;(3):785-817
Abstract
Foods and liquids have properties that are often modified as part of clinical dysphagia management to promote safe and efficient swallowing. However, recent studies have questioned whether this practice is supported by the evidence. To address this, a scoping review was conducted to answer the question: "Can properties of food and liquids modify swallowing physiology and function in adults?" Online search in six databases yielded a set of 4235 non-duplicate articles. Using COVIDENCE software, two independent reviewers screened the articles by title and abstract, and 229 full-text articles were selected for full-text review. One-hundred eleven studies met the inclusion criteria for qualitative synthesis and assessment of risk of bias. Three randomized controlled trials and 108 non-randomized studies were analyzed. Large amounts of variability in instrumental assessment, properties of food and liquids, and swallowing measures were found across studies. Sour, sweet, and salty taste, odor, carbonation, capsaicin, viscosity, hardness, adhesiveness, and cohesiveness were reported to modify the oral and pharyngeal phase of swallowing in both healthy participants and patients with dysphagia. Main swallow measures modified by properties of food and liquids were penetration/aspiration, oral transit time, lingual pressures, submental muscle contraction, oral and pharyngeal residue, hyoid and laryngeal movement, pharyngeal and upper esophageal sphincter pressures, and total swallow duration. The evidence pooled in this review supports the clinical practice of food texture and liquid consistency modification in the management of dysphagia with the caveat that all clinical endeavors must be undertaken with a clear rationale and patient-specific evidence that modifying food or liquid benefits swallow safety and efficiency while maintaining quality of life.
-
3.
Safety and immunogenicity of SARS-CoV-2 self-amplifying RNA vaccine expressing an anchored RBD: A randomized, observer-blind phase 1 study.
Akahata, W, Sekida, T, Nogimori, T, Ode, H, Tamura, T, Kono, K, Kazami, Y, Washizaki, A, Masuta, Y, Suzuki, R, et al
Cell reports. Medicine. 2023;(8):101134
Abstract
VLPCOV-01 is a lipid nanoparticle-encapsulated self-amplifying RNA (saRNA) vaccine that expresses a membrane-anchored receptor-binding domain (RBD) derived from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. A phase 1 study of VLPCOV-01 is conducted (jRCT2051210164). Participants who completed two doses of the BNT162b2 mRNA vaccine previously are randomized to receive one intramuscular vaccination of 0.3, 1.0, or 3.0 μg VLPCOV-01, 30 μg BNT162b2, or placebo. No serious adverse events have been reported. VLPCOV-01 induces robust immunoglobulin G (IgG) titers against the RBD protein that are maintained up to 26 weeks in non-elderly participants, with geometric means ranging from 5,037 (95% confidence interval [CI] 1,272-19,940) at 0.3 μg to 12,873 (95% CI 937-17,686) at 3 μg compared with 3,166 (95% CI 1,619-6,191) with 30 μg BNT162b2. Neutralizing antibody titers against all variants of SARS-CoV-2 tested are induced. VLPCOV-01 is immunogenic following low-dose administration. These findings support the potential for saRNA as a vaccine platform.
-
4.
Povidone-iodine-induced transient triiodothyronine thyrotoxicosis in a Japanese patient with prolonged habitual gargling: A case report and literature review.
Suzuki, R, Suzuki, S
Medicine. 2023;(34):e34631
-
-
Free full text
-
Abstract
RATIONALE Iodine-induced hyperthyroidism and triiodothyronine (T3) thyrotoxicosis in patients who routinely gargle with povidone-iodine (PVP-I) gargling solution are rare in Japan. PATIENT CONCERNS A 50-year-old man presented to our hospital for a close examination of an enlarged thyroid, which was noted during a complete health checkup. The thyroid was slightly enlarged with no palpable nodules. He had an increased appetite but no weight gain. He had been routinely gargling with PVP-I gargling solution 4 times daily for >10 years. He had no history of thyroid disease. DIAGNOSES Test results revealed suppressed thyroid-stimulating hormone, normal free thyroxine, and increased free triiodothyronine levels, leading to the diagnosis of T3 thyrotoxicosis. INTERVENTIONS The patient agreed to stop gargling with PVP-I gargle solution. OUTCOMES The free triiodothyronine and thyroid-stimulating hormone levels returned to normal at 18 and 21 weeks, respectively, after discontinuation of PVP-I gargling. After an improvement in thyroid function, he gained 5 kg in 1 year. LESSONS To our knowledge, this is the first case report that describes PVP-I gargle-induced T3 thyrotoxicosis in a healthy individual without thyroid disease. In Japan, which is an iodine-sufficient country, considering the possibility of high-dose iodine intake-induced thyrotoxicosis due to long-term PVP-I gargling or other causes is necessary, even in individuals with no history of thyroid disease.
-
5.
Association between tear and blood glucose concentrations: Random intercept model adjusted with confounders in tear samples negative for occult blood.
Aihara, M, Kubota, N, Minami, T, Shirakawa, R, Sakurai, Y, Hayashi, T, Iwamoto, M, Takamoto, I, Kubota, T, Suzuki, R, et al
Journal of diabetes investigation. 2021;(2):266-276
Abstract
AIMS/INTRODUCTION To prevent diabetic complications, strict glucose control and frequent monitoring of blood glucose levels with invasive methods are necessary. We considered the monitoring of tear glucose levels might be a possible method for non-invasive glucose monitoring. To develop tear glucose monitoring for clinical application, we investigated the precise correlation between the blood and tear glucose concentrations. MATERIALS AND METHODS A total of 10 participants and 20 participants with diabetes were admitted, and blood and tear samples were collected. Before statistical analysis, we eliminated tear samples contaminated with blood. We observed the daily blood and tear glucose dynamics, and carried out a random intercept model analysis to examine the association between the blood and tear glucose concentrations. RESULTS Tear occult blood tests showed that the tear glucose concentrations and their variation increased in both participants with and without diabetes as contamination of blood increased. In both participants with and without diabetes, fluctuations of the plasma glucose concentrations were observed depending on the timing of collection of the samples, and the dynamics of the tear glucose concentrations paralleled those of the plasma glucose concentrations. The random intercept model analysis showed a significant association between the plasma and tear glucose concentrations in participants with diabetes (P < 0.001). This association still existed even after adjusting for the glycated hemoglobin levels and the prandial state (P < 0.001). CONCLUSIONS It is important to eliminate the tear samples contaminated with blood. Tear glucose monitoring might be a reliable and non-invasive substitute method for monitoring the blood glucose concentrations for diabetes patients, irrespective of glycated hemoglobin levels and timing of sample collection.
-
6.
Efficacy of Sodium Carboxymethylcellulose Compared to Sodium Hyaluronate as Submucosal Injectant for Gastric Endoscopic Submucosal Dissection: A Randomized Controlled Trial.
Nakamura, J, Hikichi, T, Watanabe, K, Hashimoto, M, Kato, T, Takagi, T, Suzuki, R, Sugimoto, M, Takasumi, M, Sato, Y, et al
Digestion. 2021;(5):753-759
Abstract
INTRODUCTION Sodium hyaluronate (SH) is a useful submucosal injectant for gastric endoscopic submucosal dissection (ESD). On the other hand, sodium carboxymethylcellulose (SCMC), which has high viscosity, has also been applied clinically. We evaluated the efficacy of SCMC compared to that of SH in gastric ESD. METHODS A prospective randomized controlled trial was conducted to assess the efficacy of 1.0% SCMC as the injectant (SCMC group) compared to 0.4% SH (SH group) for ESD of gastric neoplasms. The primary end point was the procedure time of ESD. Secondary end points were treatment outcomes such as en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment (visual analog scale, 1-10 points), adverse events, and rate of ulcer healing 8 weeks after ESD. RESULTS A total of 60 patients were enrolled between October 2014 and October 2018, and 30 patients were allocated in each group. The procedure time (mean ± SD, minutes) was not significantly different between the SCMC (74.7 ± 54.5) and SH groups (67.1 ± 41.4) (p = 0.547). Furthermore, there were no differences between the 2 groups in terms of en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment, and rate of ulcer healing. No serious adverse events were observed in either group. CONCLUSION SCMC was comparable to SH in terms of procedure time, treatment outcome, and ease and safety of treatment in gastric ESD. Further studies are needed to demonstrate the differences between the 2 injectants.
-
7.
Adipose Insulin Resistance and Decreased Adiponectin Are Correlated With Metabolic Abnormalities in Nonobese Men.
Kiya, M, Tamura, Y, Takeno, K, Someya, Y, Kakehi, S, Sato, M, Yamasaki, N, Kadowaki, S, Suzuki, R, Furukawa, Y, et al
The Journal of clinical endocrinology and metabolism. 2021;(5):e2228-e2238
Abstract
CONTEXT Adipose tissue dysfunction is characterized by decreased adiponectin (AN) levels and impaired adipose tissue insulin sensitivity (ATIS) and is associated with metabolic disorders. While Asians readily develop metabolic disease without obesity, it remains unclear how decreased AN level and impaired ATIS affect metabolic abnormalities in nonobese Asians. DESIGN AND SETTING To investigate the relationships between decreased AN level, impaired ATIS, and metabolic abnormalities, we studied 94 Japanese men whose body mass index was less than 25 kg/m2. We divided the subjects into 4 groups based on their median AN level and ATIS, the latter calculated as the degree of insulin-mediated suppression of free fatty acids during hyperinsulinemic euglycemic clamp, and compared the metabolic parameters in the 4 groups. RESULTS The High-ATIS/High-AN group (n = 29) showed similar anthropometric data to the High-ATIS/Low-AN group (n = 18). In contrast, both the Low-ATIS/High-AN (n = 18) and Low-ATIS/Low-AN (n = 29) groups showed significantly lower muscle insulin sensitivity than the High-ATIS groups. The intrahepatic lipid level in the Low-ATIS/Low-AN group was significantly higher than that in the High-ATIS groups. In addition, the Low-ATIS/Low-AN group had a significantly higher fasting serum triglyceride level and significantly lower high-density lipoprotein cholesterol level than the other 3 groups. CONCLUSIONS In nonobese Japanese men with high ATIS, the AN level was not associated with metabolic characteristics. On the other hand, subjects with low ATIS showed reduced muscle insulin sensitivity, and those with a decreased AN level demonstrated multiple metabolic abnormalities, represented by fatty liver and dyslipidemia.
-
8.
Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates.
Tuan, VP, Yahara, K, Dung, HDQ, Binh, TT, Huu Tung, P, Tri, TD, Thuan, NPM, Khien, VV, Trang, TTH, Phuc, BH, et al
Microbial genomics. 2021;(11)
Abstract
Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori, which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori-related diseases.
-
9.
c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) attenuates curcumin-induced cell death differently from its family member, JNK-associated leucine zipper protein (JLP).
Gunarta, IK, Yuliana, D, Erdenebaatar, P, Kishi, Y, Boldbaatar, J, Suzuki, R, Odongoo, R, Davaakhuu, G, Hohjoh, H, Yoshioka, K
Drug discoveries & therapeutics. 2021;(2):66-72
Abstract
Curcumin, a major component of turmeric, is known to exhibit multiple biological functions including antitumor activity. We previously reported that the mitogen-activated protein kinase (MAPK) scaffold protein c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP) reduces curcumin-induced cell death by modulating p38 MAPK and autophagy through the regulation of lysosome positioning. In this study, we investigated the role of JNK/stress-activated protein kinase-associated protein 1 (JSAP1), a JLP family member, in curcumin-induced stress, and found that JSAP1 also attenuates curcumin-induced cell death. However, JSAP1 knockout showed no or little effect on the activation of JNK and p38 MAPKs in response to curcumin. In addition, small molecule inhibitors of JNK and p38 MAPKs did not increase curcumin-induced cell death. Furthermore, JSAP1 depletion did not impair lysosome positioning and autophagosome-lysosome fusion. Instead, we noticed substantial autolysosome accumulation accompanied by an inefficient autophagic flux in JSAP1 knockout cells. Taken together, these results indicate that JSAP1 is involved in curcumin-induced cell death differently from JLP, and may suggest that JSAP1 plays a role in autophagosome degradation and its dysfunction results in enhanced cell death. The findings of this study may contribute to the development of novel therapeutic approaches using curcumin for cancer.
-
10.
Protective role of c-Jun NH2-terminal kinase-associated leucine zipper protein (JLP) in curcumin-induced cancer cell death.
Boldbaatar, J, Gunarta, IK, Suzuki, R, Erdenebaatar, P, Davaakhuu, G, Hohjoh, H, Yoshioka, K
Biochemical and biophysical research communications. 2020;(3):697-703
Abstract
Previous studies have established the antitumor activity of curcumin, a major component of turmeric. Increasing evidence indicates that curcumin induces autophagy, the activation of mitogen-activated protein kinase (MAPK) intracellular signaling pathways, and reactive oxygen species (ROS)-mediated cell death. The c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP), a scaffold protein for MAPK signaling pathways, has been identified as a candidate biomarker for cancer. In this study, we explored the role of JLP in curcumin-induced cancer cell death. We found that JLP knockdown (KD) increases cell death and intracellular ROS levels. Furthermore, JLP KD impaired lysosomal accumulation around perinuclear regions, which led to the inhibition of autophagosome-lysosome fusion, and attenuated p38 MAPK activation in curcumin-treated cells. The decreases in cell viability and p38 MAPK activation were reversed by expressing wild-type JLP but not a JLP mutant lacking the p38 MAPK-binding domain. In addition, the inactivation of a key gene involved in autophagy increased sensitivity to curcumin-induced cell death. Together, these results suggest that JLP mediates the induction of autophagy by regulating lysosome positioning and p38 MAPK signaling, indicating an overall protective role in curcumin-induced ROS-mediated cancer cell death.