Objective: To compare the degree of presbyopia in ophthalmology patients before and after the 2020 COVID-19 pandemic. Methods: Near add power measurements and dry eye-related tests were performed on 349 ophthalmology patients aged 40-55 years from 2017 to 2022, and the presence of common subjective symptoms (fatigue, blurred vision, glare, dryness, discomfort, and pain) was interviewed. The subjects were first-visit patients with biocular phakic and best corrected visual acuity of 0.8 or better in both eyes, patients with glaucoma, and patients with ocular fundus diseases. Those that had undergone ophthalmic surgery within the last 30 days were excluded. Results: From 2017-2019, near add power was strongly correlated with age (β = 0.777, p < 0.001), and the estimated age of onset of presbyopia was 36.5 years, which decreased to 25.5 years in 2020 and recovered to 32.5 years in 2021. Subjective symptoms continued to worsen in both 2020 and 2021. Tear film breakup time, a dry eye-related test, and corneal damage, remained unchanged after 2020. Conclusion: The COVID-19 pandemic reduced the age of onset of presbyopia in 2020, indicating a decline in amplitude of accommodation, which recovered in 2021. Accommodation fatigue from increased near work (work that requires prolonged close-up viewing) due to increased telework and stress from changes in lifestyle and work environment are thought to be the main causes, however, we also consider the possibility that COVID-19 may accelerate aging.

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Persistent postprandial hyperglycemia contributes to increased glycative stress. Therefore, it is important to understand the effects of carbohydrates in food on postprandial glycative stress. In this study, we evaluated the effects of Yokan, a Japanese confectionery (Wagashi) made of sugar, azuki beans, and agar, on glycative stress by comparing blood glucose changes after intake of Yokan, sugar water, and rice. The subjects were 16 healthy 20 ~ 30 year men and women who attended the briefing session in advance and gave their written consent to participate in the study. The test foods were rice (A) as the reference food, Yokan (B, C, D) as the test food, and sugar water (E) with 50 g of carbohydrate, and the subsequent blood glucose changes were verified. FreeStyle Libre Pro was used for the study, and glucose concentrations in tissue interstitial fluid were measured as blood glucose levels. Blood glucose was collected prior to 120 min after intake of the test food. Results were evaluated by blood glucose change (ΔBG), maximum blood glucose (ΔCmax) and area under the glucose curve (iAUC). Study results were analyzed using multiple testing with the Bonferroni method. The study was free of adverse events and no subjects met the exclusion criteria for analysis. The glucose change curve for the 16 subjects was higher for test foods E > A > B, C, and D, in that order.ΔBG after intake of A was higher than B, C, and D at 90 and 120 min, respectively. ΔBG in B was lower than that of E after 45 min. ΔBG in C tended to be lower than that of E after 45 min. The iAUCs were higher in the order A > E > B > C > D, with significantly lower values for B, C, and D compared to A. The iAUC of D tended to be lower than that of E. The ΔCmax was higher in the order of E > D > A > B and C. The ΔCmax of B and C tended to be lower than that of E. The factors that caused the lower ΔBG, iAUC, and ΔCmax in test foods B, C, and D compared to A and E were presumed to be the effects of the azuki bean component and agar in Yokan, and changes in structure and function during food processing. From the perspective of Glycemic Index, the effects of sugar on Yokan intake were considered comparable to those of common foods. Yokan may be a functional food with less effect on glycative stress compared to rice or sugar intake if consumed in appropriate amounts.

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Keratinocytes, which make up the majority of the skin epithelium, differentiate from epidermal stem cells and migrate from the basement membrane to the upper layers of the skin, where they are finally shed as grime. Skin stem cells play an important role for skin homeostasis by proliferative capacity and flexibility in response to wound healing and physiological changes. However, factors affecting epidermal stem cell proliferation remain unresolved. In this study, we focused on Piezo1, a mechano-ion channel that recognizes "stiffness" and becomes activated, and clarified the mechanism by which the mechanical environment induces epidermal stem cell senescence. A new mechanism of skin aging has been identified in which Ptx3 expression from dermal fibroblasts increases with aging, which induces vascular atrophy and dermal stiffening, and induces age-related alterations in epidermal stem cells due to long-term calcium influx via Piezo1. This finding may be useful for the development of new functional ingredients with a novel mechanism "Ptx3 regulation."

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Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is an enzyme involved in the glycolytic pathway. From the substrates of GAPDH, toxic aldehydes, such as glyceraldehyde and methylglyoxal, can be generated. Inhibition of GAPDH in HCT116 cells by koningin acid increased glyceraldehyde. Animal experiments demonstrated that high fat diet-feeding significantly decreased mice liver GAPDH in protein level with increase of lipid peroxidation, liver damage, and shortage of liver cysteine. On the other hand, some food compounds, a water extract of chlorella and its constituent (phenethylamine), ameliorated high fat diet-induced decrease of GAPDH and following pathological events. Treatment with these compounds significantly decreased liver methylglyoxal. Cysteine can react with short chain glyceraldehydes including methylglyoxal and convert them to nontoxic metabolites. These facts indicate that decrease of GAPDH can increase toxic aldehydes in liver and induce liver damage and some food compounds can ameliorate liver damage via recovering GAPDH.

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The physiological role of amyloid-β (Aβ) is unknown, while it plays an important role in the onset and progression of Alzheimer's disease (AD). Aβ polymerization leads to enhanced neurotoxicity, persistent degradation, and deposition in the brain, resulting in decreased Aβ clearance. Diabetes mellitus and poor sleep quality are representative risk factors for the development of AD. Methylglyoxal (MGO) and acrolein are increased in diabetic patients, a representative disease with high glycative stress, and melatonin secretion is decreased during poor sleep quality. In this study, we focused on the Aβ phagocytosis of microglia, which plays a role in Aβ clearance, and examined the effects of Aβ glycation and melatonin. Glycated Aβ was prepared by MGO or acrolein treatment. Fluorescently labeled TAMRA-Aβ and primary rat microglial cells (Cosmo Bio) were used in the experiments. Several new findings were obtained from this experiment. First, microglia phagocytose Aβ, while their phagocytic capacity for glycated Aβ was markedly reduced. Second, Aβ phagocytosis was enhanced by melatonin. Concurrently, spontaneous death of cultured microglia was greater when Aβ was not added than when Aβ was. These findings suggest that prevention of Aβ glycation by countermeasures against glycative stress and prevention of AD progression by lifestyle, i.e., improvement of sleep quality, are important, rather than elimination of Aβ as has been conventionally practiced.

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S-allylcysteine (SAC) is a bioactive substance found in aged garlic and is known to improve liver function, inhibit organ fibrosis, and have anticancer activity. A single oral administration of SAC (10 mg/kg) increased tail vein blood flow in rats by up to 10% over one hour, and a 0.3% SAC mixed diet increased tail vein blood flow compared to the normal diet after 2 months. To investigate the relationship between these increases in blood flow and nitric oxide (NO), a single oral dose of SAC (100 mg/kg) followed by a 3-day administration of L-nitroarginine (LNA, 2 mM), an NO synthase inhibitor, resulted in the disappearance of SAC-induced increases in blood flow. Whereas, when LNA and excess L-arginine were mixed with drinking water, the SAC-induced increase in blood flow was restored. This phenomenon was also observed in plantar blood flow. These results indicate that the increase in blood flow induced by SAC is NO-dependent. To investigate the relationship between these increases in blood flow and NO, a single oral dose of SAC (100 mg/kg) followed by a 3-day administration of LNA (2 mM), resulted in the disappearance of SAC-induced increases in blood flow. Whereas, when LNA and excess L-arginine were mixed with drinking water, the SAC-induced increase in blood flow was restored. This phenomenon was also observed in plantar blood flow. These results indicate that the increase in blood flow by SAC is NO-dependent. Next, Western blotting of vasodilator-stimulated phosphoprotein (VASP) was performed to confirm this in a vascular model. Phosphorylated VASP (pVASP) is characterized as a substrate for both cGMP-dependent and cAMP-dependent kinases. LNA abolished the aortic pVASP band, whereas LNA plus SAC partially recovered. Focusing on the NO-independent vasodilator H2S, measurements of plasma reactive persulfide showed that LNA treatment significantly reduced thiols, i.e., cysteine, cystine, glutathione (GSH), and H2S. Of the thiols reduced by LNA treatment, the concurrent SAC application significantly restored the reduction of cysteine and cystine, but not H2S. These results suggest that SAC may maintain nitrosothiols (compounds of nitric oxide and thiols) that act as NO donors and indirectly increase the bioavailability of NO, resulting in blood flow augmentation through its antioxidant capacity by free radical scavenging.

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Background and objective: Plant-derived glucosylceramides (GlcCer) have been clinically reported to enhance skin barrier functions. GlcCer and ceramides (Cer) interact with immune-stimulating receptors on antigen-presenting cells, such as c-type lectin receptors and toll-like receptor 4. However, the clinical and immunological efficacies of orally ingested GlcCer remain unknown. Therefore, we herein conducted a clinical trial on the effects of rice-derived GlcCer (Oryza Ceramide^®: OC) on cold symptoms, immune parameters, and SF-36 scores. Methods: OC (type PCD, 60 mg daily) containing 1.8 mg of GlcCer and 0.09 mg of Cer [t18:0/24:0] was used as the active sample. We enrolled 44 healthy Japanese individuals who are prone to catching colds and a low immune score. All subjects were randomly allocated to an active group (n = 22) or placebo group (n = 22). Capsules containing OC or the placebo were administered for 8 weeks. Cold symptom scores during the intervention were the primary outcome, while immune parameters and SF-36 scores measured after the 8-week intervention were the secondary outcomes. Results: Forty subjects completed the trial, and the per protocol set comprised 19 and 21 in the active and placebo groups, respectively. Regarding the primary outcome, cumulative days with cold symptoms, such as nasal congestion, throat irritation, a cough, headache, muscle pain, and diarrhea, was lower in the OC group. Among the secondary outcomes, physical functioning in SF-36 scores was improved in the OC group. Regarding immune parameters, a negative correlation was observed between changes in blood T-lymphocytes and cumulative days with cold symptoms. Laboratory tests revealed no abnormalities to suggest adverse effects of OC. Conclusions: OC consisting of GlcCer attenuated typical cold symptoms, such as nasal congestion, throat irritation, a cough, headache, muscle pain, and diarrhea, and improved physical conditions. Changes in T-lymphocytes may be one of the mechanisms by which OC ameliorates cold symptoms.

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Purpose: Advanced glycation endproducts (AGEs) are involved in age-related deterioration of vascular function. In our clinical study, we evaluated the vascular stiffness of mangosteen pericarp (water extract of mangosteen: WEM), which has an inhibitory effect on the formation of AGEs, and found a trend toward improvement in vascular stiffness, however the improvement was not significant. Factors that affect vascular function include age, blood glucose, blood pressure, and low-density-lipoprotein-cholesterol (LDL-C) or triglycerides (TG). In the present study, we examined the effect of WEM on vascular flexibility by performing a stratified analysis focusing on factors that affect vascular function. In the present study, we performed a stratified analysis focusing on factors affecting vascular function and examined the effect of WEM on vascular flexibility. Methods: In a previous report, 38 women (19 in the WEM group and 19 in the placebo group) aged 25 to 59 years were administered WEM (200 mg) or a placebo for 12 weeks, and blood tests and vascular function tests were performed before, 4, 8, and 12 weeks after intake in a placebo-controlled, double-blind, randomized, parallel-group comparison study. Whereas, in the present study, we reanalyzed the results of the above studies, focusing on factors affecting vascular function (age, blood glucose, blood pressure, and LDL-C or TG). First, we excluded subjects who exceeded the scope indicated in Attachment 2, "Points to Consider in Preparing Application Forms for Foods for Specified Health Use" of "Permission for Labeling of Foods for Specified Health Use" (Notice No. 109 of April 1, 2020, by the Deputy Director-General of the Consumer Affairs Agency). Next, we reanalyzed the effect of WEM on vascular stiffness by selecting subjects who were at least 30 years of age, had borderline blood glucose, normal hypertension and I-degree hypertension, borderline and mild LDL-C, and normal high and slightly high TG, respectively. Vascular stiffness was assessed by PASESA AVE-1500 (Shisei Datum, Japan), API (Arterial Pressure Index) and AVI (Arterial Velocity Pulse Index) in the right upper arm. Results: Subjects with blood LDL-C levels above (>160 mg/dL) those in the mild disease range were excluded (2 subjects in the WEM group and 4 subjects in the placebo group). Subjects with blood glucose levels of 110 ~ 125 mg/dL, systolic blood pressure of 130 ~ 159 mmHg or diastolic blood pressure of 85 ~ 99 mmHg, and TG of 120-199 mg/dL were not extracted for analysis. There were 7 subjects in the WEM group and 9 subjects in the placebo group with an LDL-C of 120~ 159 mg/dL, but no significant difference in API and AVI. 14 subjects in the WEM intake group and 13 subjects in the placebo group aged 30 years or older could be extracted, and WEM intake significantly reduced API after 8 and 12 weeks of intake. However, there was no difference in AVI. Conclusion: The results of this reanalysis results showed that WEM intake, which inhibits glycation, reduced API in healthy women aged 30 years or older. This suggests that WEM intake alleviates age-related vascular stiffening and maintains flexibility.

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Aim: Glycation reactions involve the binding of sugars to amino groups of proteins to form advanced glycation end products (AGEs) via glycation intermediates. AGEs induce inflammatory and protein dysfunctions, leading to diabetes and skin aging. The aim of this study was to evaluate the anti-glycation effect of holy basil (Ocimum tenuiflorum) leaf extract and identify the compounds responsible for these effects. Methods: The crude extract was obtained by hot water extraction of dried holy basil leaves. The total polyphenol and flavonoid contents and antioxidant activities of the crude extract were determined. Phenolic compounds were isolated from the crude extract using various chromatographic methods. The effect of the crude extract and isolated compounds on the formation of fluorescent AGEs, N^ε-(carboxymethyl) lysine (CML), 3-deoxyglucosone (3-DG), glyoxal (GO), and methylglyoxal (MGO) were examined. Results: The crude extract of holy basil was rich in polyphenols, most of which were flavonoids. Luteolin 5-O-glucoside (1), luteolin 7-O-glucuronide (2), (−)-rabdosiin (3), apigenin 7-O-glucuronide (4), rosmarinic acid (5), globoidnan A (6), and salvianolic acid A (7) isolated from the crude extract inhibited the formation of fluorescent AGEs, CML, 3-DG, GO, and MGO. In particular, compounds 3, 5, 6, and 7 were potent antiglycation compounds. The crude extract also showed high antioxidant activities. Conclusions: Phenolic compounds of holy basil were found to be the active components endowing antiglycative effects. One of the antiglycation mechanisms of these polyphenols could be related to the antioxidant action of holy basil.

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