BACKGROUND/OBJECTIVES: Brain aging is a major risk factor for severe neurodegenerative diseases. Conversely, L-histidine and L-carnosine are known to exhibit neuroprotective effects. The aim of this study was to examine the potential for L-histidine, L-carnosine, and their combination to mediate anti-brain aging effects in neuronal cells subjected to D-galactose-induced aging.MATERIALS/METHODS: The neuroprotective potential of L-histidine, L-carnosine, and their combination was examined in a retinoic acid-induced neuronal differentiated SH-SY5Y cell line exposed to D-galactose (200 mM) for 48 h. Neuronal cell proliferation, differentiation, and expression of anti-oxidant enzymes and apoptosis markers were subsequently evaluated. RESULTS: Treatment with L-histidine (1 mM), L-carnosine (10 mM), or both for 48 h efficiently improved the proliferation, neurogenesis, and senescence of D-galactose-treated SH-SY5Y cells. In addition, protein expression levels of both neuronal markers (β tubulin-III and neurofilament heavy protein) and anti-oxidant enzymes, glutathione peroxidase-1 and superoxide dismutase-1 were up-regulated. Conversely, protein expression levels of amyloid β (1-42) and cleaved caspase-3 were down-regulated. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-8, IL-1β, and tumor necrosis factor-α were also down-regulated. CONCLUSIONS To the best of our knowledge, we provide the first evidence that L-histidine, L-carnosine, and their combination mediate anti-aging effects in a neuronal cell line subjected to D-galactose-induced aging. These results suggest the potential benefits of L-histidine and L-carnosine as anti-brain aging agents and they support further research of these amino acid molecules.

BACKGROUND: Beta-carotene (BC) is a carotenoid which exerts anti-cancer effects in several types of cancer, including colorectal cancer. Epigenetic modifications of genes, such as histone deacetylation and DNA hypermethylation, have also been detected in various types of cancer. To understand the molecular mechanism underlying cancer preventive and therapeutic effects of BC, microRNAs (miRNAs), histone acetylation, and global DNA methylation in colon cancer stem cells (CSCs) were investigated.METHODS: HCT116 colon cancer cells positive for expression of CD44 and CD133 were sorted by flow cytometry and used in subsequent experiments. Cell proliferation was examined by the MTT assay and self-renewal capacity was analyzed by the sphere formation assay. The miRNA sequencing array was used to detect miRNAs regulated by BC. Histone acetylation levels were measured by the Western blot analysis. mRNA expression of DNA methyltransferases (DNMTs) was examined by qPCR and global DNA methylation levels were determined by enzyme-linked immunosorbent assay.RESULTS: Treatment of CD44⁺CD133⁺ colon CSCs with BC caused a reduction in both cell proliferation and sphere formation. Analysis of the miRNA sequencing array showed that BC regulated expression of miRNAs associated with histone acetylation. Histone H3 and H4 acetylation levels were elevated by BC treatment. In addition, BC treatment down-regulated DNMT3A mRNA expression and global DNA methylation in colon CSCs.CONCLUSIONS: These results suggest that BC regulates epigenetic modifications for its anti-cancer effects in colon CSCs.
Acetylation ; beta Carotene ; Blotting, Western ; Cell Proliferation ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; DNA Methylation ; DNA ; Enzyme-Linked Immunosorbent Assay ; Epigenomics ; Flow Cytometry ; Histones ; Methyltransferases ; MicroRNAs ; RNA, Messenger ; Stem Cells ; Therapeutic Uses

BACKGROUND/OBJECTIVES: Brain senescence causes cognitive impairment and neurodegeneration. It has also been demonstrated that curcumin (Cur) and hesperetin (Hes), both antioxidant polyphenolic compounds, mediate anti-aging and neuroprotective effects. Therefore, the objective of this study was to investigate whether Cur, Hes, and/or their combination exert anti-aging effects in D-galactose (Dg)-induced aged neuronal cells and rats.MATERIALS/METHODS: SH-SY5Y cells differentiated in response to retinoic acid were treated with Cur (1 μM), Hes (1 μM), or a combination of both, followed by 300 mM Dg.Neuronal loss was subsequently evaluated by measuring average neurite length and analyzing expression of β-tubulin III, phosphorylated extracellular signal-regulated kinases, and neurofilament heavy polypeptide. Cellular senescence and related proteins, p16 and p21, were also investigated, including their regulation of antioxidant enzymes. In vivo, brain aging was induced by injecting 250 mg/kg body weight (b.w.) Dg. The effects of supplementing this model with 50 mg/kg b.w. Cur, 50 mg/kg b.w. Hes, or a combination of both for 3 months were subsequently evaluated. Brain aging was examined with a step-through passive avoidance test and apoptosis markers were analyzed in brain cortex tissues. RESULTS: Cur, Hes, and their combination improved neuron length and cellular senescence by decreasing the number of β-gal stained cells, down-regulated expression of p16 and p21, and up-regulated expression of antioxidant enzymes, including superoxide dismutase 1, glutathione peroxidase 1, and catalase. Administration of Cur, Hes, or their combination also tended to ameliorate cognitive impairment and suppress apoptosis in the cerebral cortex by downregulating Bax and poly (ADP-ribose) polymerase expression and increasing Bcl-2 expression. CONCLUSIONS Cur and Hes appear to attenuate Dg-induced brain aging via regulation of antioxidant enzymes and apoptosis. These results suggest that Cur and Hes may mediate neuroprotective effects in the aging process, and further study of these antioxidant polyphenolic compounds is warranted.

BACKGROUND/OBJECTIVES: Bitter taste receptors are taste signaling pathway mediators, and are also expressed and function in extra-gustatory organs. Skin aging affects the quality of life and may lead to medical issues. The purpose of this study was to better understand the anti-skin aging effects of bitter taste receptors in D-galactose (D-gal)-induced aged human keratinocytes, HaCaT cells.MATERIALS/METHODS: Expressions of bitter taste receptors in HaCaT cells and mouse skin tissues were examined by polymerase chain reaction assay. Bitter taste receptor was overexpressed in HaCaT cells, and D-gal was treated to induce aging. We examined the effects of bitter taste receptors on aging by using β-galactosidase assay, wound healing assay, and Western blot assay. RESULTS: TAS2R16 and TAS2R10 were expressed in HaCaT cells and were upregulated by D-gal treatment. TAS2R16 exerted protective effects against skin aging by regulating p53 and p21, antioxidant enzymes, the SIRT1/mechanistic target of rapamycin pathway, cell migration, and epithelial-mesenchymal transition markers. TAS2R10 was further examined to confirm a role of TAS2R16 in cellular senescence and wound healing in D-gal-induced aged HaCaT cells. CONCLUSIONS Our results suggest a novel potential preventive role of these receptors on skin aging by regulating cellular senescence and wound healing in human keratinocyte, HaCaT.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the cartilage and subchondral bone, leading to temporomandibular joint pain and dysfunction. The complex nature of TMJOA warrants effective alternative treatments, and mesenchymal stem cells (MSCs) have shown promise in regenerative therapies. The aim of this study is twofold: firstly, to ascertain the optimal interferon-gamma (IFN-γ)-primed MSC cell line for TMJOA treatment, and secondly, to comprehensively evaluate the therapeutic efficacy of IFN-γ-primed mesenchymal stem cells derived from the human umbilical cord matrix in a rat model of TMJOA. METHODS: We analyzed changes in the expression of several key genes associated with OA protection in MSC-secreted compounds. Following this, we performed co-culture experiments using a transwell system to predict gene expression changes in primed MSCs in the TMJOA environment. Subsequently, we investigated the efficacy of the selected IFN-γ-primed human umbilical cord matrix-derived MSCs (hUCM-MSCs) for TMJOA treatment in a rat model. RESULTS: IFN-γ-primed MSCs exhibited enhanced expression of IDO, TSG-6, and FGF-2. Moreover, co-culturing with rat OA chondrocytes induced a decrease in pro-inflammatory and extracellular matrix degradation factors. In the rat TMJOA model, IFN-γ-primed MSCs with elevated IDO1, TSG-6, and FGF2 expression exhibited robust anti-inflammatory and therapeutic capacities, promoting the improvement of the inflammatory environment and cartilage regeneration. CONCLUSION These findings underscore the importance of prioritizing the mitigation of the inflammatory milieu in TMJOA treatment and highlight IFN-γ-primed MSCs secreting these three factors as a promising, comprehensive therapeutic strategy.

The inhalation of naphthalene used as deodorant balls in public toilets could be an important cancer risk factor. The atmospheric concentration of naphthalene in public toilets (C(in)) was estimated both by a polyurethane foam passive air sampler (PUF-PAS) deployed in nine public toilets in Seoul, Korea and by a steady-state indoor air quality model, including emission estimation using Monte-Carlo simulation. Based on the estimated C(in), cancer risk was also assessed for cleaning workers and the general population. The steady-state C(in) estimated using the estimated emission rate, which assumed that air exchange was the only process by which naphthalene was removed, was much greater than the C(in) value measured using PUF-PAS in nine public toilets, implying the importance of other removal processes, such as sorption to walls and the garments of visitors, as well as decreased emission rate owing to wetting of the naphthalene ball surface. The 95 percentile values of cancer risk for workers based on the estimation by PUF-PAS was 1.6×10⁻⁶, whereas those for the general public were lower than 1×10⁻⁶. The results suggested that naphthalene deodorant balls in public toilets may be an important cancer risk factor especially for the cleaning workers.
Air Pollution, Indoor ; Clothing ; Deodorants ; Inhalation Exposure ; Inhalation ; Korea ; Polyurethanes ; Risk Assessment ; Risk Factors ; Seoul

The inhalation of naphthalene used as deodorant balls in public toilets could be an important cancer risk factor. The atmospheric concentration of naphthalene in public toilets (C(in)) was estimated both by a polyurethane foam passive air sampler (PUF-PAS) deployed in nine public toilets in Seoul, Korea and by a steady-state indoor air quality model, including emission estimation using Monte-Carlo simulation. Based on the estimated C(in), cancer risk was also assessed for cleaning workers and the general population. The steady-state C(in) estimated using the estimated emission rate, which assumed that air exchange was the only process by which naphthalene was removed, was much greater than the C(in) value measured using PUF-PAS in nine public toilets, implying the importance of other removal processes, such as sorption to walls and the garments of visitors, as well as decreased emission rate owing to wetting of the naphthalene ball surface. The 95 percentile values of cancer risk for workers based on the estimation by PUF-PAS was 1.6×10⁻⁶, whereas those for the general public were lower than 1×10⁻⁶. The results suggested that naphthalene deodorant balls in public toilets may be an important cancer risk factor especially for the cleaning workers.
Air Pollution, Indoor ; Clothing ; Deodorants ; Inhalation Exposure ; Inhalation ; Korea ; Polyurethanes ; Risk Assessment ; Risk Factors ; Seoul

The inhalation of naphthalene used as deodorant balls in public toilets could be an important cancer risk factor. The atmospheric concentration of naphthalene in public toilets (C(in)) was estimated both by a polyurethane foam passive air sampler (PUF-PAS) deployed in nine public toilets in Seoul, Korea and by a steady-state indoor air quality model, including emission estimation using Monte-Carlo simulation. Based on the estimated C(in), cancer risk was also assessed for cleaning workers and the general population. The steady-state C(in) estimated using the estimated emission rate, which assumed that air exchange was the only process by which naphthalene was removed, was much greater than the C(in) value measured using PUF-PAS in nine public toilets, implying the importance of other removal processes, such as sorption to walls and the garments of visitors, as well as decreased emission rate owing to wetting of the naphthalene ball surface. The 95 percentile values of cancer risk for workers based on the estimation by PUF-PAS was 1.6×10⁻⁶, whereas those for the general public were lower than 1×10⁻⁶. The results suggested that naphthalene deodorant balls in public toilets may be an important cancer risk factor especially for the cleaning workers.

Purpose: This study investigated the effects of healthy lifestyle interventions (HLSIs) on health-related quality of life (HR-QoL) in childhood and adolescent cancer survivors (CACS). Methods: Major databases were searched for English-language original articles published between January 1, 2000 and May 2, 2021. Randomized controlled trials (RCTs) and non-RCTs were included. Quality was assessed using the revised Cochrane risk-of-bias tool, and a meta-analysis was conducted using RevMan 5.3 software. Results: Nineteen studies were included. Significant effects on HR-QoL were found for interventions using a multi-modal approach (exercise and education) (d=-0.46; 95% confidence interval [CI]=-0.84 to -0.07, p=.02), lasting not less than 6 months (d=-0.72; 95% CI=-1.15 to -0.29, p=.0010), and using a group approach (d=-0.46; 95% CI=-0.85 to -0.06, p=.02). Self-efficacy showed significant effects when HLSIs provided health education only (d=-0.55; 95% CI=-0.92 to -0.18; p=.003), lasted for less than 6 months (d=-0.40; 95% CI=-0.69 to -0.11, p=.006), and were conducted individually (d=-0.55; 95% CI=-0.92 to -0.18, p=.003). The physical outcomes (physical activity, fatigue, exercise capacity-VO2, exercise capacity-upper body, body mass index) revealed no statistical significance. Conclusion Areas of HLSIs for CACS requiring further study were identified, and needs and directions of research for holistic health management were suggested.

Objectives: We reviewed the operational definitions of colorectal cancer (CRC) from studies using the Korean National Health Insurance Service (NHIS) and compared CRC incidence derived from the commonly used operational definitions in the literature with the statistics reported by the Korea Central Cancer Registry (KCCR). Methods: We searched the MEDLINE and KoreaMed databases to identify studies containing operational definitions of CRC, published until January 15, 2021. All pertinent data concerning the study period, the utilized database, and the outcome variable were extracted. Within the NHIS-National Sample Cohort, age-standardized incidence rates (ASRs) of CRC were calculated for each operational definition found in the literature between 2005 and 2019. These rates were then compared with ASRs from the KCCR. Results: From the 62 eligible studies, 9 operational definitions for CRC were identified. The most commonly used operational definition was “C18-C20” (n=20), followed by “C18-C20 with claim code for treatment” (n=3) and “C18-C20 with V193 (code for registered cancer patients’ payment deduction)” (n=3). The ASRs reported using these operational definitions were lower than the ASRs from KCCR, except for “C18-C20 used as the main diagnosis.” The smallest difference in ASRs was observed for “C18-C20,” followed by “C18- C20 with V193,” and “C18-C20 with claim code for hospitalization or code for treatment.” Conclusions In defining CRC patients utilizing the NHIS database, the ASR derived through the operational definition of “C18-C20 as the main diagnosis” was comparable to the ASR from the KCCR. Depending on the study hypothesis, operational definitions using treatment codes may be utilized.