Epstein-Barr Virus-Positive Mucocutaneous Ulcer on the Gingiva of a Patient in Whom Immunosuppressive Drugs Could Not Be Withdrawn: A Case Report and Review of the Literature.

Epstein-Barr virus-positive mucocutaneous ulcer (EBV-MCU) is characterized by ulcers confined to the skin and mucus membranes. EBV-MCU is an EBV-positive lymphoproliferative disorder that occurs during the use of immunosuppressive drugs such as methotrexate. We herein report a case of EBV-MCU in the maxillary gingiva. A 73-year-old woman was referred to our department in March 2021. During the initial examination, bone exposure and ulceration were observed in the extraction socket of the maxillary bilateral central incisors. The patient was taking methotrexate for rheumatoid arthritis and was unable to stop due to disease progression. In March 2021, curettage of the extraction socket of the maxillary anterior teeth and extraction of the maxillary right lateral incisor, which was difficult to preserve due to severe tooth mobility, was performed under local anesthesia. The extraction site epithelialized and healed well. Three months later, inflammation flared, and ulceration was observed. Extraction of the unsalvageable maxillary teeth and an excisional biopsy of the palatal gingiva were performed. The histopathological diagnosis was EBV-MCU. The postoperative course was uneventful, and no evidence of recurrence was found two years postoperatively; follow-up will be continued. There are many reports of EBV-MCU remission with the cessation of methotrexate treatment. In our patient, withdrawal was difficult because of the progression of rheumatoid arthritis, but remission was achieved by improving the oral cavity environment through an excisional biopsy and tooth extraction.

Biomineralization through a Symmetry-Controlled Oligomeric Peptide.

Biomineralization peptides are versatile tools for generating nanostructures since they can make specific interactions with various inorganic metals, which can lead to the formation of intricate nanostructures. Previously, we examined the influence that multivalency has on inorganic structures formed by p53 tetramer-based biomineralization peptides and noted a connection between the geometry of the peptide and its ability to regulate nanostructure formation. To investigate the role of multivalency in nanostructure formation by biomineralization peptides more thoroughly, silver biomineralization peptides were engineered by linking them to additional self-assembling molecules based on coiled-coil peptides and multistranded DNA oligomers. Under mild reducing conditions at room temperature, these engineered biomineralization peptides self-assembled and formed silver nanostructures. The trimeric forms of the biomineralization peptides were the most efficient in forming a hexagonal disk nanostructure, with both the coiled-coil peptide and DNA-based multimeric forms. Together, the results suggest that the spatial arrangement of biomineralization peptides plays a more important role in regulating nanostructure formation than their valency.

Association between fluid overload and delirium/coma in mechanically ventilated patients.

AIM: Several studies have shown an association between fluid overload (FO) and mortality or duration of mechanical ventilation in critically ill patients. However, the association between FO and delirium duration remains unclear. METHODS: This retrospective observational cohort study was undertaken at University of Tsukuba Hospital (Tsukuba, Japan) from April 2015 to March 2017. Mechanically ventilated patients who stayed in the intensive care unit for more than 7 days were eligible for inclusion. Univariate analysis was carried out with the Mann-Whitney U-test for continuous variables and Fisher's exact test for categorical variables. A multivariate proportional odds logistic regression model was used to evaluate the association between FO and delirium/coma days (DCDs) during the 7-day study period. RESULTS: A total of 118 patients were included and divided into FO and non-FO groups. Fluid overload occurred in 40% of patients. The FO group had a higher APACHE II score than the non-FO group (19 [16-26] versus 23 [20-29], P = 0.017). Cumulative fluid balance at day 3 was higher in the FO group (3,238 [281-6,530] versus 7,886 [4,106-10,631], P < 0.001). Delirium days within 7 days was longer in the FO group (1 [0-3] versus 2 [1-3], P = 0.048) and DCDs was longer in the FO group (4 [1-5] versus 6 [3-7], P = 0.002). After adjusting for covariates, there were significant associations between FO and DCDs (odds ratio, 2.16; 95% confidence interval, 1.05-4.47). CONCLUSIONS: Our findings suggest that FO is associated with increased DCDs in mechanically ventilated patients.

Dipeptide synthesis by internal adenylation domains of a multidomain enzyme involved in nonribosomal peptide synthesis.

The adenylation domain of nonribosomal peptide synthetase (NRPS) is responsible for its selective substrate recognition and activation of the substrate (yielding an acyl-O-AMP intermediate) on ATP consumption. DhbF is an NRPS involved in bacillibactin synthesis and consists of multiple domains [adenylation domain, condensation domain, peptidyl carrier protein (PCP) domain, and thioesterase domain]; DhbFA1 and DhbFA2 (here named) are "internal" adenylation domains in the multidomain enzyme DhbF. We firstly succeeded in expressing and purifying the "internal" adenylation domains DhbFA1 and DhbFA2 separately. Furthermore, we initially demonstrated dipeptide synthesis by "internal" adenylation domains. When glycine and L-cysteine were used as substrates of DhbFA1, the formation of N-glycyl-L-cysteine (Gly-Cys) was observed. Furthermore, when L-threonine and L-cysteine were used as substrates of DhbFA2, N-L-threonyl-L-cysteine (Thr-Cys) was formed. These findings showed that both adenylation domains produced dipeptides by forming a carbon-nitrogen bond comprising the carboxyl group of an amino acid and the amino group of L-cysteine, although these adenylation domains are acid-thiol ligase using 4'-phosphopantetheine (bound to the PCP domain) as a substrate. Furthermore, DhbFA1 and DhbFA2 synthesized oligopeptides as well as dipeptides.

Synergic Strategies for the Enhanced Self-Assembly of Biomineralization Peptides for the Synthesis of Functional Nanomaterials.

INTRODUCTION: Peptide-mediated biomineralization is a promising bioinspired technique of nanostructure formation. The biomineralization peptide is responsible for the regulation of the growth and morphology of the inorganic nanostructure. The 3D properties of the biomineralization peptide is a crucial factor in which the success of creating functional nanomaterials depends on. However, given the relatively short sequence of most biomineralization peptides, controlling the multivalency and spatial orientation of the peptide can be a challenging endeavor. OBJECTIVE: This mini-review details recent advances in enhancing the self-assembly and 3D properties of the biomineralization peptide. The design and creation of fusion peptides is highlighted, which involves the conjugation of the biomineralization peptide with a control element. The control element is responsible for directing the self-assembly of the biomineralization peptide. CONCLUSION: A variety of control elements that can direct the self-assembly of biomineralization peptides are available. The control element can be a small organic molecule such as a biphenyl, or a peptide segment such as the p53 tetramerization domain or the amyloid peptide. The high diversity of existing control elements further increases the ability of peptide-mediated biomineralization to create functional nanomaterials.

Oligomerization enhances the binding affinity of a silver biomineralization peptide and catalyzes nanostructure formation.

Binding affinity and specificity are crucial factors that influence nanostructure control by biomineralization peptides. In this paper, we analysed the role that the oligomeric state of a silver biomineralization peptide plays in regulating the morphology of silver nanostructure formation. Oligomerization was achieved by conjugating the silver specific TBP biomineralization peptide to the p53 tetramerization domain peptide (p53Tet). Interestingly, the TBP-p53Tet tetrameric peptide acted as a growth catalyst, controlling silver crystal growth, which resulted in the formation of hexagonal silver nanoplates without consuming the peptide. The TBP-p53Tet peptide caps the surface of the silver crystals, which enhances crystal growth on specific faces and thereby regulates silver nanostructure formation in a catalytic fashion. The present findings not only provide an efficient strategy for controlling silver nanostructure formation by biomineralization peptides, but they also demonstrate that in this case the oligomeric peptides play a unique catalytic role.

N-butanol extracts of Morinda citrifolia suppress advanced glycation end products (AGE)-induced inflammatory reactions in endothelial cells through its anti-oxidative properties.

BACKGROUND: Advanced glycation end products (AGEs), senescent macroprotein derivatives formed during a normal aging process and acceleratedly under diabetic conditions, play a role in atherosclerotic cardiovascular disease. AGEs cause endothelial cell (EC) damage, an initial trigger for atherosclerosis through the interaction with a receptor for AGEs (RAGE). We have previously shown that n-butanol extracts of Morinda citrifolia (noni), a plant belonging to the family Rubiaceae, block the binding of AGEs to RAGE in vitro. In this study, we examined the effects of n-butanol extracts of noni on reactive oxygen species (ROS) generation and inflammatory reactions on AGE-exposed human umbilical vein ECs (HUVECs). METHODS: HUVECs were treated with 100 µg/ml AGE-bovine serum albumin (AGE-BSA) or non-glycated BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni for 4 h. Then ROS generation and inflammatory and gene expression in HUVECs were evaluated by dihydroethidium staining and real-time reverse transcription-polymerase chain reaction analyses, respectively. THP-1 cell adhesion to HUVECs was measured after 2-day incubation of AGE-BSA or BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni. RESULTS: N-butanol extracts of noni at 670 ng/ml significantly inhibited the AGE-induced ROS generation and RAGE, intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 gene expressions in HUVECs. AGEs significantly increased monocytic THP-1 cell adhesion to HUVECs, which was also prevented by 670 ng/ml n-butanol extracts of noni. CONCLUSIONS: The present study demonstrated for the first time that N-butanol extracts of noni could suppress the AGE-induced inflammatory reactions in HUVECs through its anti-oxidative properties via blocking of the interaction of AGEs with RAGE. Inhibition of the AGE-RAGE axis by n-butanol extracts of noni may be a novel nutraceutical strategy for the treatment of cardiovascular disease.

Phytochemicals Against Advanced Glycation End Products (AGEs) and the Receptor System.

Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and function, contributing to aging-related organ damage and diabetes-associated complications, such as cardiovascular disease (CVD). Moreover, engagement of receptor for AGEs, RAGE with the ligands evoke oxidative stress generation and inflammatory, thrombotic and fibrotic reactions in various kinds of tissues, further exacerbating the deleterious effects of AGEs on multiple organ systems. So the AGE-RAGE axis is a novel therapeutic target for numerous devastating disorders. Several observational studies have shown the association of dietary consumption of fruits and vegetables with the reduced risk of CVD in a general population. Although beneficial effects of fruits and vegetables against CVD could mainly be ascribed to its anti-oxidative properties, blockade of the AGERAGE axis by phytochemicals may also contribute to cardiovascular event protection. Therefore, in this review, we focus on 4 phytochemicals (quercetin, sulforaphane, iridoids, and curcumin) and summarize their effects on AGE formation as well as RAGE-mediated signaling pathway in various cell types and organs, including endothelial cells, vessels, and heart.

Effects of biomineralization peptide topology on the structure and catalytic activity of Pd nanomaterials.

Highly branched, coral-like Pd nanostructures were formed using a biomineralization peptide conjugated to an oligomeric peptide that simultaneously controls the spatial orientation, arrangement and valency. The Pd nanocoral showed very high catalytic activity in the reduction of nitrophenol. The results highlight the importance of topological arrangement in nanostructure formation and catalytic activity.