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The global prevalence of oral squamous cell carcinoma (OSCC) has been increasing. OSCC at the advanced stage tends to resist conventional treatment and causes local recurrence and distant metastasis, resulting in poor prognosis. Therefore, detecting this cancer at an early stage and performing early intervention are important. Promising biomarkers to detect OSCC have yet to be established; however, microRNAs (miRNAs/miRs) serve a crucial role in OSCC tumorigenesis and may be potential biomarkers. In the present case report, the availability of salivary miRNAs as a therapeutic and prognostic marker for patients with OSCC was assessed. The patient was a 33-year-old woman who was diagnosed with advanced OSCC of the tongue, and their miRNA profile isolated from a saliva sample at each clinical course was evaluated. Microarray analysis of the salivary samples revealed changes in the levels of four miRNAs (hsa-miR-6798-5p, miR-6803-5p, miR-6805-5p and miR-6845-5p) in accordance with the clinical course. Neoadjuvant chemotherapy and surgical procedure decreased the levels, whereas the levels increased when the patient was diagnosed with lung metastasis. Furthermore, tongue and lung metastatic lesion specimens exhibited expression of the vascular endothelial growth factor receptor-2, which is regulated by the four miRNAs. Accordingly, the present report proposed that salivary miRNAs could be a therapeutic and prognostic biomarker for OSCC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Kimura et al.)

Background: The activity level of alkaline phosphatase, a zinc-requiring enzyme in the serum, is used to indicate zinc nutritional status; however, it does not correlate with serum zinc levels or subjective symptoms of taste disorder in many cases. Hence, this study focused on the total activity of alkaline phosphatase, a zinc-requiring enzyme. The total alkaline phosphatasa activity level in the saliva was measured before and after zinc supplementation, and the results were compared with serum zinc levels., Case Presentation: This study included patients with hypozincemia, specifically a patient with zinc-deficient taste disorder (patient 1: a 69-year-old Japanese woman) and a patient with glossodynia with zinc deficiency (patient 2: an 82-year-old Japanese woman). Saliva samples were collected, and blood tests were performed before and after zinc supplementation. Subjective symptoms and serum zinc levels were simultaneously evaluated. Zinc supplementation was performed using zinc acetate hydrate or Polaprezinc., Conclusions: Total alkaline phosphatase activity levels were found to be associated with serum zinc levels and subjective symptoms. A further study with a higher number of patients is necessary to confirm whether total alkaline phosphatase activity levels more accurately reflect the amounts of zinc in the body than serum zinc levels., (© 2024. The Author(s).)

Objective: This study aimed to elucidate the difference in virulence of Candida albicans derived from oral candidiasis and non-oral candidiasis patients, and its genotype differences in Hokkaido to obtain a clue of a platform to develop new approaches for diagnosis and treatment., Design: C. albicans strains were collected from patients who visited the Hokkaido University Hospital Dental Center. Each strain was examined to i) identify the Candida albicans genotype by PCR, ii) measure the strain's extracellular secretory enzyme activity, iii) determine the strain's ability to induce the production of interleukin-8, and iv) determine the strain's ability to induce cell death., Results: Certain virulence-related protease activities and cytotoxicity were higher in strains derived from patients with oral candidiasis compared with strains derived from patients without oral candidiasis. This is the first report on genotypes and the virulence-related activities, such as some protease secretion, IL-8 induction and cytotoxicity of C. albicans in Hokkaido., Conclusions: The virulence-related activities of the fungal strain may influence the pathogenesis of oral candidiasis, such as production of secreted aspartyl protease and cytotoxicity. In addition, C. albicans genotype C may be important for pathogenicity in Hokkaido, because the ratio of genotype C was increased in strains derived from oral candidiasis patients., Competing Interests: Declaration of Competing Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background/purpose: Delayed healing of the extraction socket is not uncommon when tooth extraction is performed on patients taking prednisolone. This study aimed to identify specific dosage of prednisolone and factors associated with delayed healing of the extraction socket in patients taking prednisolone., Materials and Methods: This single-center retrospective study included 80 patients who underwent tooth extraction under local anesthesia and were taking prednisolone orally. Patients were divided into the nondelayed healing group ( n  = 50) and delayed healing group ( n  = 30), and their background and dosage of prednisolone were compared., Results: The dosage of prednisolone was significantly higher in the delayed healing group than in the nondelayed healing group. A receiver operating characteristics curve analysis resulted in moderate accuracy when the cutoff value was set at 8.0, with 67% sensitivity, 76% specificity, and 0.765 area under the curve. The multivariate logistic regression analysis revealed that prednisolone dosage >8.0 mg/day (odds ratio [OR], 10.8; 95% confidence interval [CI], 2.79-41.6) and osteosclerotic changes beyond the alveolar bone around the tooth to be extracted (OR, 10.3; 95% CI, 2.81-37.8) in X-ray imaging had significant effects on delayed healing., Conclusion: The results of this study suggested that delayed healing following tooth extractions in patients taking prednisolone was related to a dosage of 8.0 mg/day or higher and osteosclerotic changes., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

The principle of microscopic reversibility says that, in equilibrium, two-time cross-correlations are symmetric under the exchange of observables. Thus, the asymmetry of cross-correlations is a fundamental, measurable, and often-used statistical signature of deviation from equilibrium. Here we find a simple and universal inequality that bounds the magnitude of asymmetry by the cycle affinity, i.e., the strength of thermodynamic driving. Our result applies to a large class of systems and all state observables, and it suggests a fundamental thermodynamic cost for various nonequilibrium functions quantified by the asymmetry. It also provides a powerful tool to infer affinity from measured cross-correlations, in a different and complementary way to the thermodynamic uncertainty relations. As an application, we prove a thermodynamic bound on the coherence of noisy oscillations, which was previously conjectured by Barato and Seifert [Phys. Rev. E 95, 062409 (2017)PRESCM2470-004510.1103/PhysRevE.95.062409]. We also derive a thermodynamic bound on directed information flow in a biochemical signal transduction model.

We construct an information-geometric structure for chemical thermodynamics, applicable to a wide range of chemical reaction systems including nonideal and open systems. For this purpose, we explicitly construct dual affine coordinate systems, which completely designate an information-geometric structure, using the extent of reactions and the affinities of reactions as coordinates on a linearly constrained space of amounts of substances. The resulting structure induces a metric and a divergence (a function of two distributions of amounts), both expressed with chemical potentials. These quantities have been partially known for ideal-dilute solutions, but their extensions for nonideal solutions and the complete underlying structure are novel. The constructed geometry is a generalization of dual affine coordinates for stochastic thermodynamics. For example, the metric and the divergence are generalizations of the Fisher information and the Kullback-Leibler divergence. As an application, we identify the chemical-thermodynamic analog of the Hatano-Sasa excess entropy production using our divergence.

Background: Ethyl loflazepate (EL) is a benzodiazepine derivative that has been reported to activate the gustatory cortex. Our department routinely uses EL as a first-line treatment for idiopathic and psychogenic taste disorders, although little has been reported in the literature with respect to patient outcomes, so we conducted a retrospective study examining its safety and efficacy., Methods: Between 2008 and 2020, 49 patients (14 males and 35 females; mean age, 62.1 years) were diagnosed with taste disorders and received EL as their only treatment for > 14 days. Severity of taste disorder was evaluated using the paper disc method by Sakai et al., and treatment efficacy was evaluated using the Visual Analog Scale, wherein patients gave subjective ratings for their symptoms (reductions by > 50% after administration of EL for 4 weeks were defined as improvements)., Results: Results showed that the improvement rates for patients with idiopathic and psychogenic taste disorders were 55 and 70%, respectively. Additionally, the majority (78%) improved within 2 weeks, and side effects were mild (seven cases with drowsiness and one case with dizziness)., Conclusions: We conclude that EL is an appropriate first-line medication for patients with idiopathic and psychogenic taste disorders., (© 2022. The Author(s).)

Tumor blood vessels play important roles in tumor progression and metastasis. Targeting tumor endothelial cells (TECs) is one of the strategies for cancer therapy. We previously reported that biglycan, a small leucine-rich proteoglycan, is highly expressed in TECs. TECs utilize biglycan in an autocrine manner for migration and angiogenesis. Furthermore, TEC-derived biglycan stimulates tumor cell migration in a paracrine manner leading to tumor cell intravasation and metastasis. In this study, we explored the therapeutic effect of biglycan inhibition in the TECs of renal cell carcinoma using an in vivo siRNA delivery system known as a multifunctional envelope-type nanodevice (MEND), which contains a unique pH-sensitive cationic lipid. To specifically deliver MEND into TECs, we incorporated cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) into MEND because α V β 3 integrin, a receptor for cRGD, is selective and highly expressed in TECs. We developed RGD-MEND-encapsulating siRNA against biglycan. First, we confirmed that MEND was delivered into OS-RC-2 tumor-derived TECs and induced in vitro RNAi-mediated gene silencing. MEND was then injected intravenously into OS-RC-2 tumor-bearing mice. Flow cytometry analysis demonstrated that MEND was specifically delivered into TECs. Quantitative RT-PCR indicated that biglycan was knocked down by biglycan siRNA-containing MEND. Finally, we analyzed the therapeutic effect of biglycan silencing by MEND in TECs. Tumor growth was inhibited by biglycan siRNA-containing MEND. Tumor microenvironmental factors such as fibrosis were also normalized using biglycan inhibition in TECs. Biglycan in TECs can be a novel target for cancer treatment., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Basal cell carcinoma (BCC) is the most common cancer worldwide. Most of BCCs can be detected in the early stages and are generally well controlled with local resection. Despite the high incidence of BCC, metastasis is rarely observed. Metastatic BCCs generally have an aggressive phenotype and are refractory to conventional treatment., Case Presentation: We describe a rare case of BCC in which a series of local relapses culminated in metastasis into the oral cavity 10 years after the first diagnosis of cutaneous BCC. We performed surgical resection and postoperative radiotherapy in this patient; 11 months after the final course of radiotherapy, the BCC remains stable, and the patient continues to be monitored regularly., Conclusions: Because metastatic BCC is refractory to current treatment and difficult to control, his treatment history and the pathohistological features of BCC had to be considered in posttreatment planning., (© 2022. The Author(s).)