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Coconut milk contains plant-based saturated fat and phytochemicals with antioxidant activities. However, its role in breast cancer risk remains unclear. A case-control study was conducted on 244 participants to study the association. The Case group includes 61 newly diagnosed breast cancer patients receiving < 6 months of therapies. The Control group includes 183 healthy people with matched characteristics. A new questionnaire was developed, validated, and used in this study to estimate the frequency of coconut milk-containing food intake. Results show that the questionnaire has satisfactory content validity, test-retest reliability, and criterion-related validity. From the case-control study, either consuming 1-3 or 4-6 times/week of coconut-milk-containing curry or consuming 4-6 times/week of coconut milk-topped desserts are associated with increased risk of breast cancer (OR = 5.23, 5.6, and 2.6 respectively, p  < 0.01). Consuming less than half of coconut milk liquid in desserts correlated with a reduced risk (OR = 0.43, p  < 0.05). The findings suggest that moderate (less than half of a serving) and infrequent (less than once a week) consumption of coconut milk may be beneficial for breast cancer prevention. A larger scale study is warranted to confirm the findings and provide evidence for dietary recommendations.

Reactive oxygen species (ROS) in biological systems are transient but essential molecules that are generated and eliminated by a complex set of delicately balanced molecular machineries. Disruption of redox homeostasis has been associated with various human diseases, especially cancer, in which increased ROS levels are thought to have a major role in tumour development and progression. As such, modulation of cellular redox status by targeting ROS and their regulatory machineries is considered a promising therapeutic strategy for cancer treatment. Recently, there has been major progress in this field, including the discovery of novel redox signalling pathways that affect the metabolism of tumour cells as well as immune cells in the tumour microenvironment, and the intriguing ROS regulation of biomolecular phase separation. Progress has also been made in exploring redox regulation in cancer stem cells, the role of ROS in determining cell fate and new anticancer agents that target ROS. This Review discusses these research developments and their implications for cancer therapy and drug discovery, as well as emerging concepts, paradoxes and future perspectives., (© 2024. Springer Nature Limited.)

Bergaptol (5-hydroxypsoralen or 5-hydroxyfuranocoumarin) is a naturally occurring furanocoumarin widely found in citrus fruits, which has multiple health benefits. Nonetheless, no specific review articles on bergaptol have been published. Compiling updated information on bergaptol is crucial in guiding future research direction and application. The present review focuses on the research evidence related to the pharmacological properties and toxicity of bergaptol. Bergaptol has anti-inflammatory, antioxidant, anti-cancer, anti-osteoporosis, anti-microbial, and anti-lipidemic effects. It can inhibit the activities of cytochrome P450s (CYP), especially CYP2C9 and CYP3A4, thereby affecting the metabolism and concentrations of some drugs and toxins. Compared with other coumarins, bergaptol has the least potency to inhibit CYP3A4 in cancer cells. Instead, it can suppress drug efflux transporters, such as P-glycoprotein, thereby overcoming chemotherapeutic drug resistance. Furthermore, bergaptol has antimicrobial effects with a high potential for inhibition of quorum sensing. In vivo, bergaptol can be retained in plasma for longer than other coumarins. Nevertheless, its toxicity has not been clearly reported. In vitro study suggests that, unlike most furocoumarins, bergaptol is not phototoxic or photomutagenic. Existing research on bergaptol has mostly been conducted in vitro. Further in vivo and clinical studies are warranted to identify the safe and effective doses of bergaptol for its multimodal application.

Glucosinolates in Brassica vegetables can be hydrolyzed into various products, e.g., chemopreventive agents, isothiocyanates (ITCs) and anti-thyroid substance, goitrin. Cooking can reduce goitrin but destroy isothiocyanates. This study aimed to optimize cooking conditions for reducing goitrin while preserving isothiocyanates in Brassica vegetables. Cabbage and Chinese kale samples were divided evenly into raw, blanched, steamed, and water-based stir-fried samples. Cooking temperature and time were varied at 60, 80, or 100 °C for 2, 4, or 6 min. The levels of goitrin, benzyl isothiocyanate (BITC), and sulforaphane (SFN) were measured using LC-MS/MS. Response surface model (RSM) was used to identify the optimal cooking conditions to reduce goitrin but preserve ITCs. Results showed that goitrin content in cabbage depended on the cooking methods, temperature, and time, while that of Chinese kale only depended on the methods. In contrast, the concentrations of SFN in cabbage and BITC in kale depended on the cooking temperature and time but not methods. Based on RSM analysis, the suggested household cooking methods for preserving isothiocyanates and reducing goitrin are steaming cabbage at 80-100 °C for 4 min and stir-frying Chinese kale at 60-100 °C for 2 min. Such methods may preserve the bioactive compounds while reducing food hazards.

Background: Elevated inflammation and negative nutritional balance contribute to sarcopenia, a progressive loss of muscle mass, strength, and function. This study investigated the effect of energy supplementation and the combination of anti-inflammatory factor (eicosapentaenoic acid; EPA) and muscle-synthesis promotor (branched-chain amino acids; BCAA) on body composition, muscle, and inflammatory biomarkers in elderly with inadequate protein intake., Methods: A randomized blinded placebo-controlled trial was conducted on 84 elderly with inadequate protein intake. The participants were randomly assigned into four groups receiving a complete nutrition drink; (1) control formula, (2) fortified with 2.2 g EPA, (3) with 2.2 g EPA and 5 g BCAA (2:1:1 of Leu: Ile: Val), and (4) with 2.2 g EPA plus 5g BCAA (4:1:1 of Leu: Ile: Val). Each subject consumed two sachets of the drink to gain 500 kcal/day and performed arm muscle exercises for 3 weeks. Body compositions and handgrip strength were measured using BIA and a dynamometer, respectively. Plasma EPA and BCAA levels were determined using LC-MS/MS to ensure compliance. Muscle protein biomarkers including histidine, β-alanine, and carnosine were measured using LC-MS/MS. Serum inflammatory (IL-6) and anti-inflammatory cytokines (IL-10) were measured by using ELISA., Results: No symptoms and signs of adverse events were observed. The right arm muscle mass and handgrip strength were significantly increased after consuming a complete nutrition drink fortified with EPA + BCAA 2:1:1 and 4:1:1 of Leu: Ile: Val ( p < 0.05 and p < 0.01, respectively. Consistently, consuming such combinatory formula non-significantly elevated carnosine with reduced histidine, and increased IL-10 with decreased IL-6. All relevant intervention groups showed a significant increase in plasma levels of BCAA and EPA., Conclusion: Consuming a complete nutrition drink fortified with 2.2g EPA and 5g BCAA 2:1:1 or 4:1:1 of Leu: Ile: Val for 3 weeks may increase right arm muscle mass and strength in elderly with inadequate protein intake. The tendency of increased dipeptide (carnosine)/decreased free amino acid (histidine) suggests a shift toward muscle protein synthesis. The trend of decreased inflammatory/increased anti-inflammatory cytokines suggests an anti-inflammatory effect. Future long-term studies are warranted to confirm the combinatory effect of BCAA and EPA in the prevention of sarcopenia., Clinical Trial Registration: Thailand Clinical Trial Registry No. TCTR20230116005., Competing Interests: DT received research grant from a governmental funding agency, Thailand Science Research and Innovation (TSRI), and a private company, Thai Otsuka Pharmaceutical Co., Ltd., Thailand. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khoonin, Shantavasinkul, Santivarangkna, Praengam and Trachootham.)

TP53 mutation is associated with cancer progression. Novel strategies to reboot p53 are required to stabilize the disease and improve survival. This randomized placebo-controlled trial investigated safety and efficacy of Nutri-PEITC Jelly (a texture-modified nutritious diet fortified with β-phenethyl isothiocyanate (PEITC) on oral cancer. Seventy-two patients with advanced-staged oral or oropharyngeal cancer were randomly assigned to study and control groups, who consumed 200 g of Nutri-Jelly with and without 20 mg of PEITC, respectively, 5 days/week for 12 weeks. Outcomes, including adverse events, health-related quality of life (HRQOL), progression-free survival (PFS), tumor response, serum p53, and cytochrome c, were measured at 0, 1, and 3 months. Results show that the study group had a higher proportion of participants with improved HRQOL, stable disease, and increased serum p53 levels than those in the control group ( p < 0.001). The PFS time in the study group was significantly longer than that of the control group ( p < 0.05). Serum cytochrome c levels were non-significantly decreased in the study group. No serious intervention-related adverse events occurred in either group. In conclusion, Nutri-PEITC Jelly intake for 3 months is safe, stabilizes the disease, improves quality of life and progression-free survival, and might re-activate p53 in advanced-stage oral and oropharyngeal cancer patients.

Lime peels are food waste from lime product manufacturing. We previously developed and optimized a green extraction method for hesperidin-limonin-rich lime peel extract. This study aimed to identify the metabolomics profile of phytochemicals and the anti-cancer effects of ethanolic extract of lime ( Citrus aurantifolia ) peel against liver cancer cells PLC/PRF/5. The extract's metabolomics profile was analyzed by using LC-qTOF/MS and GC-HRMS. The anti-cancer effects were studied by using MTT assay, Annexin-PI assay, and Transwell-invasion assay. Results show that the average IC 50 (s) of hesperidin, limonin, and the extract on cancer cells' viability were 165.615, 188.073, and 503.004 µg/mL, respectively. At the IC 50 levels, the extract induced more apoptosis than those of pure compounds when incubating for 24 and 48 h ( p < 0.0001). A combination of limonin and hesperidin showed a synergistic effect on apoptosis induction ( p < 0.001), but the effect of the combination was still less than that of the extract at 48 h. Furthermore, the extract significantly inhibited cancer cell invasion better than limonin but equal to hesperidin. At the IC 50 level, the extract contains many folds lower amounts of hesperidin and limonin than the IC 50 doses of the pure compounds. Besides limonin and hesperidin, there were another 60 and 22 compounds detected from the LCMS and GCMS analyses, respectively. Taken altogether, the superior effect of the ethanolic extract against liver cancer cells compared to pure compound likely results from the combinatorial effects of limonin, hesperidin, and other phytochemical components in the extract.

Coffee cherry pulp, a major waste product from coffee manufacturing, contains polyphenols with antioxidant activity. However, its clinical safety and health benefits are unclear. This randomized, double-blinded, placebo-controlled trial evaluated the safety and potential efficacy of coffee cherry pulp juice concentrate. A total of 61 participants were randomly divided into a study group ( n = 30), receiving the juice, and a control group ( n = 31), receiving a placebo drink of 14 g twice daily for 12 weeks. Adverse symptoms, changes in body weight, hematological and biochemical parameters, vital signs, and heart function were evaluated using subject diaries, interviews, blood and urine tests, and electrocardiograms. The results showed no intervention-related adverse events. Body weight, liver, renal function, complete blood counts, blood glucose, urinalysis, and electrocardiograms were not significantly altered throughout the study. Consuming the juice for at least 8 weeks significantly decreased cholesterol and LDL levels. The glucose levels were maintained significantly better than those of the placebo group. The findings suggest that continuously consuming 28 g/day of coffee pulp juice concentrate for 12 weeks is safe in healthy volunteers. Future studies could employ a dose of ≤28 g/day to investigate the efficacy of this novel food, especially for preventing dyslipidemia and diabetes.

Since legalization, cannabis/marijuana has been gaining considerable attention as a functional ingredient in food. ∆-9 tetrahydrocannabinol (THC), cannabidiol (CBD), and other cannabinoids are key bioactive compounds with health benefits. The oral consumption of cannabis transports much less hazardous chemicals than smoking. Nevertheless, the response to cannabis is biphasically dose-dependent (hormesis; a low-dose stimulation and a high-dose inhibition) with wide individuality in responses. Thus, the exact same dose and preparation of cannabis may be beneficial for some but toxic to others. The purpose of this review is to highlight the concept of individual variations in response to cannabinoids, which leads to the challenge of establishing standard safe doses of cannabis products for the general population. The mechanisms of actions, acute and chronic toxicities, and factors affecting responses to cannabis products are updated. Based on the literature review, we found that the response to cannabis products depends on exposure factors (delivery route, duration, frequency, and interactions with food and drugs), individual factors (age, sex), and susceptibility factors (genetic polymorphisms of cannabinoid receptor gene, N-acylethanolamine-hydrolyzing enzymes, THC-metabolizing enzymes, and epigenetic regulations). Owing to the individuality of responses, the safest way to use cannabis-containing food products is to start low, go slow, and stay low.

Retort sterilization is cost-effective for small-scale production of specialized nutrition products. However, the sensory properties and stability of active ingredients after sterilization remain undetermined. This study aimed to investigate the effect of retort on the existence of functional compounds and the sensory satisfaction of a fortified complete nutrition formula with branched-chain amino acids (BCAAs), and fish oil providing eicosapentaenoic acid (EPA). Changes in EPA and BCAA contents after retort were determined by using LC-MS/MS. Nutrient values, osmolality, rheology and sensory acceptance of the processed fortified and control formulas were compared. After retort, the fortified formula had an increase in all types of BCAAs but 30% loss of EPA ( p = 0.001). The fortified formula had slightly higher protein and fiber contents, along with increased osmolality. It had higher viscosity and shear stress, but similar IDDSI level at 0. Among flavors tested, the fortified formula with Japanese rice flavor received the highest satisfaction scores with over 80% sensory acceptance. In conclusion, retort sterilization preserved BCAAs of the functional drink, but the addition of 30% fish oil was required to compensate for the EPA loss. The sterilized fortified formula with Japanese rice flavor was sensory acceptable.

Many types of cancer have metabolic alterations with increased glycolysis. Identification of alternative sweeteners that do not fuel cancer is a novel approach to cancer control. The present study aimed to investigate the effects of xylitol on tumor growth and survival of mice bearing orthotopic xenograft of tongue cancers. The results showed that partial substitution of glucose with xylitol (glucose 0.35 g plus xylitol 2.06 g/kg body weight) non-significantly reduced tumor volume, and significantly prolonged the median survival time from 19 days in the control to 30.5 days in the xylitol group. Immunohistochemical data of the tongue tissue shows significantly lower intense-to-mild staining ratios of the proliferation marker Ki-67 in the xylitol than those of the control group ( p = 0.04). Furthermore, the xylitol substitution significantly reduced the expression of the rate-limiting glycolytic enzyme, phosphofructokinase-1 (PFK-1) ( p = 0.03), and showed a non-significant inhibition of PFK activity. In summary, partial substitution of glucose with xylitol at the equivalent dose to human household use of 10 g/day slows down tumor proliferation and prolongs survival of mice bearing an orthotopic oral cancer xenograft, possibly through glycolytic inhibition, with minimal adverse events. The insight warrants clinical studies to confirm xylitol as a candidate sweetener in food products for cancer survivors.

Complete nutrition drinks with a low glycemic index (GI) provide nutritional support and prevent hyperglycaemia. The present study identified GI and factors predicting individual glucose response to a new complete nutrition drink. A randomised cross-over controlled trial was conducted in eighteen healthy volunteers (FPG < 100 mg/dl). Complete nutrition drinks containing retrograded starch, glucose solution and white bread were assigned in a random sequence with 14-day wash-out intervals. Plasma glucose and insulin levels were measured from baseline to 180 min after consuming each food. Results show the adjusted GIs of the drink was 48.2 ± 10.4 and 46.7 ± 12.7 with glucose and white bread as the reference, respectively. While the drink has low GI (<55), the individual glucose responses varied (GI: 7-149). Comparing characters in individual GI < 55 ( n = 12) and GI ≥ 55 ( n = 6) groups revealed significantly higher baseline insulin in the low GI group (14.86 ± 16.51 μIU/ml v . 4.9 ± 3.4 μIU/ml, P < 0·05). The correlation matrix confirms only two predictive factors for having individual GI <55 were baseline insulin ( r = 0·5, P = 0·03) and HOMA-IR ( r = 0·55, P = 0·02). ROC curve reveals fasting insulin above 1.6 μIU/ml and HOMA-IR above 1.05 as the cut-off values. The findings suggest that the complete nutrition drink has a low GI, but there was wide variability in individual responses partly explained by fasting insulin levels and HOMA-IR. Screening for fasting insulin and HOMA-IR may be encouraged to maximise the functional benefit of the drink., (© The Author(s) 2022.)

Green extraction is aimed at reducing energy consumption by using renewable plant sources and environmentally friendly bio-solvents. Lime ( Citrus aurantifolia ) is a rich source of flavonoids (e.g., hesperidin) and limonoids (e.g., limonin). Manufacturing of lime products (e.g., lime juice) yields a considerable amount of lime peel as food waste that should be comprehensively exploited. The aim of this study was to develop a green and simple extraction method to acquire the highest yield of both limonin and hesperidin from the lime peel. The study method included ethanolic-aqueous extraction and variable factors, i.e., ethanol concentrations, pH values of solvent, and extraction temperature. The response surface methodology was used to optimize extraction conditions. The concentrations of limonin and hesperidin were determined by using UHPLC-MS/MS. Results showed that the yields of limonin and hesperidin significantly depended on ethanol concentrations and extraction temperature, while pH value had the least effect. The optimal extraction condition with the highest amounts of limonin and hesperidin was 80% ethanol at pH 7, 50 °C, which yields 2.072 and 3.353 mg/g of limonin and hesperidin, respectively. This study illustrates a green extraction process using food waste, e.g., lime peel, as an energy-saving source and ethanol as a bio-solvent to achieve the highest amount of double bioactive compounds.

Alzheimer's disease (AD), one type of dementia, is a complex disease affecting people globally with limited drug treatment. Thus, natural products are currently of interest as promising candidates because of their cost-effectiveness and multi-target abilities. Diplazium esculentum (Retz.) Sw., an edible fern, inhibited acetylcholinesterase in vitro, inferring that it might be a promising candidate for AD treatment by supporting cholinergic neurons. However, evidence demonstrating anti-AD properties of this edible plant via inhibiting of neurotoxic peptides production, amyloid beta (Aβ), both in vitro and in vivo is lacking. Thus, the anti-AD properties of D. esculentum extract both in vitro and in Drosophila models of Aβ-mediated toxicity were elucidated. Findings showed that an ethanolic extract exhibited high phenolics and flavonoids, contributing to antioxidant and inhibitory activities against AD-related enzymes. Notably, the extract acted as a BACE-1 blocker and reduced amyloid beta 42 (Aβ42) peptides in Drosophila models, resulting in improved locomotor behaviors. Information gained from this study suggested that D. esculentum showed potential for AD amelioration and prevention. Further investigations in vertebrates or humans are required to determine the effective doses of D. esculentum against AD, particularly via amyloidogenic pathway., (© 2021. The Author(s).)

Heterocyclic aromatic amines (HAAs) including PhIP and MeIQx are potential carcinogens found mainly in well-done meat. Consuming brassica vegetables was shown to promote metabolisms of HAAs due to the action of isothiocyanates. Previous in vivo studies showed that phenethyl isothiocyanate (PEITC) was a potent stimulator of phase II detoxification enzymes. Nevertheless, the clinical effect of PEITC-rich vegetables on detoxification of HAAs in grilled meat was unknown. This research aimed to investigate the effect of a PEITC-rich vegetable sauce on the detoxification of HAAs in healthy people consuming grilled meat. A randomized crossover placebo-controlled trial was conducted in twenty-one healthy participants. They were randomly assigned into three groups. The participants consumed a single meal of grilled beef with 100 g of the placebo sauce and 100 g and 50 g of the vegetable sauce. All participants consumed all sauces in an alternating random sequence. After de-conjugation with β-glucuronidase, the HAA metabolites in urine were measured by using LC/MS-MS. Compared to the placebo sauce, consuming grilled beef with 100 g of the vegetable sauce increased the urinary excretion of both PhIP and MeIQx glucuronide metabolites ( p -value <0.0001), while consuming 50 g of the sauce significantly increased only MeIQx metabolites ( p -value <0.05). The findings of this study suggested that consuming grilled meat with 100 g of the PEITC-rich vegetable sauce could increase the urinary excretion of PhIP and MeIQx glucuronide metabolites. Since meat eaters usually consume a low amount of vegetables, the PEITC-rich vegetable sauce could be an alternative approach to provide detoxification benefits from vegetable-derived compounds.

Alcohol consumption leads to acetaldehyde accumulation, especially in people with mutant aldehyde dehydrogenase 2 gene ( ALDH2 ). Novel strategies to promote acetaldehyde detoxification are required to prevent alcohol-related toxicity. Probiotic bacteria such as Lactobacillus rhamnosus GG (LGG) were shown to have in vitro capacity to detoxify acetaldehyde. This randomized, blinded, placebo-controlled cross-over trial investigated the effect of LGG fermented milk in people with ALDH2 polymorphisms after moderate alcohol intake. Ten healthy wild-type and ten heterozygous mutant ALDH2 Thai men were block randomized into two groups. Each group consumed a different sequence of 150 mL fermented milk containing 10 8 CFU mL -1 LGG and lactic-acidified milk (placebo), followed by five glasses of beer (0.4 g ethanol per kg body weight), with a one-week wash-out. Consuming LGG fermented milk before alcohol reduced areas under the response curves of blood and salivary acetaldehyde in wild-type and heterozygous mutant ALDH2 individuals ( p < 0.05 and p < 0.01, respectively). Interestingly, participants with mutant ALDH2 responded better than wild-type participants for salivary acetaldehyde (90% vs. 70%, p < 0.001). Their durations of flushing were reduced when consuming LGG milk. Regardless of ALDH2 status, 10 5 CFU mL -1 LGG was retained in saliva at least 3.5 h after milk consumption. In conclusion, intake of LGG fermented milk before drinking alcohol reduces blood and salivary acetaldehyde levels and duration of flushing in drinkers with wild-type and heterozygous mutant ALDH2 . The addition of exogenous capacity to detoxify acetaldehyde using the probiotic product could be a potential strategy to promote the alleviation of exposure to reactive and carcinogenic acetaldehyde associated with alcohol drinking in individuals with defective ALDH2 enzyme.

Objectives: The aim of this study was to investigate the association between taste and smell losses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and to elucidate whether taste preference influences such taste loss., Methods: A matched case-control study was conducted in 366 Thai participants, including 122 who were confirmed SARS-CoV-2-positive by RT-PCR (case group) and 244 who were SARS-CoV-2-negative (control group). Taste, smell, and appetite changes were assessed by self-reported visual analog scale. Preference for sweet, salty, umami, sour, bitter, and spicy were judged using the validated TASTE-26 questionnaire., Results: Partial taste and smell losses were observed in both groups, while complete losses (ageusia and anosmia) were detected only in the case group. Moreover, only ageusia and anosmia were associated with SARS-CoV-2 positivity (P < 0.001, odds ratio of 14.5 and 27.5, respectively). Taste, smell, and appetite scores were more severely reduced in the case group (P < 0.0001). Multivariate analysis showed that anosmia and ageusia were the best predictors of SARS-CoV-2 positivity, followed by appetite loss and fever. Simultaneous losses of taste and smell but not taste preferences were associated with SARS-CoV-2 positivity (P < 0.01, odds ratio 2.28)., Conclusions: Complete, but not partial, losses of taste and smell were the best predictors of SARS-CoV-2 infection. During the current COVID-19 pandemic, healthy persons with sudden simultaneous complete loss of taste and smell should be screened for COVID-19., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the efficacy of an edible artificial saliva gel, oral moisturizing jelly (OMJ), and a topical commercial gel (GC dry mouth gel) on Candida colonization and saliva properties., Materials and Methods: This study was a secondary analysis of a single-blinded randomized controlled trial conducted in xerostomic post-radiotherapy head and neck cancer patients. Candida colonization, stimulated salivary flow rate (SSFR), saliva pH, and buffering capacity (BC) were measured at 0, 1, and 2 months after each intervention. Candida colonization was quantified by colony counts and species identified by Candida Chromagar, polymerase chain reaction, and API 20C AUX system. Statistical significance level was 0.05., Results: A total of 56 participants in OMJ (N = 30) and GC (N = 26) groups completed the study. OMJ significantly increased saliva pH (p = 0.042) and BC (p = 0.013) after 1-month use, while GC only improved saliva pH (p = 0.027). Both interventions tended to increase SSFR but only GC had a significant increase at 2 months (p = 0.015). GC and OMJ significantly decreased the number of Candida species at 1 and 2 months, respectively. Both groups tended to reduce Candida counts but not significant., Conclusions: Both OMJ and GC saliva gels could improve saliva pH and decrease the number of Candida species. OMJ is superior to GC in its buffering capacity, while GC may better improve salivary flow rate. Long-term and large-scale study is warranted to test the efficacy of artificial saliva in oral health improvement., Clinical Relevance: OMJ and GC gel could decrease the number of Candida species and improve saliva properties in post-radiation xerostomic patients., Trial Registration Number: Clinicaltrials.gov NCT03035825. Date of registration: 25th January 2017.

Purpose: The aim of this study is to investigate the effect of an edible saliva substitute, oral moisturizing jelly (OMJ), and a topical saliva gel (GC) on dry mouth, swallowing ability, and nutritional status in post-radiotherapy head and neck cancer patients., Methods: Sixty-two post-radiation head and neck cancer patients with xerostomia completed a blinded randomized controlled trial. They were advised to swallow OMJ (n = 31) or apply GC orally (n = 31) for 2 months. Outcome measures were assessed at baseline, 1, and 2 months, including subjective and objective dry mouth (Challcombe) scores, subjective swallowing problem scores (EAT-10), water swallowing time, clinical nutritional status (PG-SGA), body weight, and dietary intake., Results: After 1 and 2 months of interventions, subjective and objective dry mouth scores, subjective swallowing problem scores, swallowing times, and clinical nutritional status in both groups were significantly improved (p < 0.0001). Compared to GC, OMJ group had higher percent improvement in all outcome measures (p < 0.001) except swallowing time and clinical nutritional status. Interestingly, subjective dry mouth scores were significantly correlated with subjective swallowing problem scores (r = 0.5321, p < 0.0001)., Conclusions: Continuous uses of saliva substitutes (OMJ or GC) for at least a month improved signs and symptoms of dry mouth and enhanced swallowing ability. An edible saliva substitute was superior to a topical saliva gel for alleviating dry mouth and swallow problems. These lead to improved clinical nutritional status. Thus, palliation of dry mouth may be critical to support nutrition of post-radiotherapy head and neck cancer patients., Clinical Trial Registry: Clinicaltrials.gov NCT03035825.

Objectives: To evaluate (a) oral colonization of Candida species, especially for non-albicans Candida species (NACS), in xerostomic postradiotherapy head and neck cancer patients and (b) risk factors affecting their colonization., Materials and Methods: Subjective and objective dry mouth scores, stimulated salivary flow rates, pH and buffering capacity were measured in 72 xerostomic postradiotherapy head and neck cancer patients. Candida counts and species identification were performed using oral rinse samples cultured in Candida Chromagar, followed by polymerase chain reaction and API 20C AUX system., Results: Candida colonization was observed in 87.5% of subjects, with 80.6% and 48.6% of study population colonized by C. albicans and NACS, respectively. NACS was associated with high objective dry mouth scores, denture use, and females (p = .006, .009, and .036, respectively). In addition, Candida glabrata was detected more in females (p = .018) and denture wearers (p = .026), while Candida tropicalis was associated with high objective dry mouth scores (p = .022) and females (p = .027). Quantity of Candida colonization correlated positively with objective dry mouth scores (r = 0.599, p < .001) and negatively with salivary flow rates (r = -0.258, p = .041) and pH (r = -0.290, p = .022)., Conclusion: NACS colonization was common in xerostomic head and neck cancer patients. Increased signs of dry mouth, female and dental prostheses may promote NACS colonization., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Toxic element exposure increases risk of neurodevelopmental disorders. However, hair element profiles of well-nourished urban resident children were largely unknown. We identified prevalence and the contributing factors of high hair aluminum (Al), arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) levels in 111 Thai children (aged 3-7 years old). Most participants were well-nourished with high socioeconomic status. Since ROC curve of hair element data showed inadequate sensitivity for cutoff set-up, US reference hair levels were used to categorize high and low level groups. Nevertheless, compared to the current reference at 5 μg/dL, blood lead cutoff at 2.15 μg/dL provided more consistent results with that of hair lead levels. High As and Pb levels were the first and second most prevalent element, while Al was the element found in highest amount in hair. High hair Al (12% prevalence) levels were associated with being male regardless of age or nutritional status. High hair As levels were associated with living in Bangkok (OR = 6.57) regardless of school type. High hair Pb levels were associated with being under 5 years old and living in Bangkok (OR = 3.06). However, no associations were found between blood Pb, hair Cd, Hg, and tested factors. These findings suggested that under 5-year-old boys living in capital city like Bangkok may be at risk of exposure to multiple toxic elements. Future studies in these children are warranted to identify their exposure sources and proper risk management strategies.

Weight loss is common in cancer patients underwent radiation therapy. However, the impact of pretreatment behavior on postradiation nutritional status was unknown. This prospective observational study was conducted in 31 Thai head and neck cancer patients to investigate the association between pretreatment dietary preference and weight change after radiotherapy. Pretreatment preferences on sweet, salty, sour, bitter, umami, spicy, and fatty food were evaluated using a validated questionnaire, TASTE26. Body weights were monitored at baseline, 1,000-2,000, 2,800-3,400, 4,000-4,400, and 5,000-7,000 cGy of radiations and 2 month-follow up after radiotherapy. The energy intakes were analyzed by using 3 day-dietary record and INMUCAL software. Spicy food preference was the only factor found positively correlated with weight loss after radiation (r = 0.64, P = 0.007). Consistently, strong spicy lovers had more pronounced reduction of energy intake and body weight, and higher needs of tube feeding than those of mild or moderate lovers (P < 0.05). This study suggested that stronger preference on spicy food may be associated with less energy intake and more severe weight loss after radiation therapy. A large-scale study is warranted to confirm such findings. Then, preradiation screening for spicy preference may be useful to predict weight loss during radiation therapy.

Background and Objectives: Swallowing difficulty and diabetes mellitus are common in the elderly. However, texture-modified foods suitable for blood sugar control are scarce. This study was aimed to identify texture, glycemic indices (GIs) and postprandial responses of original and high-fiber Riceberry rice puddings., Methods and Study Design: International Dysphagia Diet Standard Initiative (IDDSI)'s methods were used to determine texture. In vitro digestion was performed for estimating glycemic indices. A randomized cross-over controlled trial was conducted in twelve healthy volunteers. Original pudding, high-fiber pudding and white bread containing 40 g carbohydrate each were assigned in random sequence with twelve-day wash-out intervals. Plasma glucose concentrations were measured at 0, 15, 30, 60, 90, 120, 150, and 180 min after food intake. Individual GIs of puddings were calculated., Results: Original and high-fiber puddings were classified as IDDSI level 3 (liquidized) and 4 (pureed), respectively. The in vitro estimated GIs were 51 for original and 48 for high-fiber puddings. Clinical trial showed rapid kinetics (peaked at 30 min) but lower postprandial responses of both puddings, compared to white bread (peaked at 60 min). The adjusted GIs for original and high-fiber puddings were not significantly different (at 41±7.60 and 36±6.40, respectively)., Conclusions: Addition of fiber to the original pudding changed physical properties but not significantly reduced the GI. Original and high-fiber Riceberry rice puddings could be low-GI dysphagia diets, which may be useful for step-wise swallowing practice from IDDSI level 3 to 4 for those who also required blood sugar control.

High doses of β-phenylethyl isothiocyanate (PEITC), a phytochemical in cruciferous vegetables, are not feasible for consumption due to a strong mouth-tingling effect. This study investigated the anti-cancer effect of PEITC at sensory acceptable doses. In vitro, PEITC was selectively toxic to oral cancer cells (CAL-27, FaDu, SCC4, SCC 9, SCC15, SCC25 and TU138), compared to oral keratinocytes (OKF6/TERT2 and NOK/Si). In vivo, 5 and 10 mg kg-1 PEITC, equivalent to human organoleptically acceptable doses, retarded tumor growth and prolonged the survival of mice bearing p53-mutated oral cancer cells - TU138 xenograft. Mechanistically, PEITC induced ROS accumulation, nuclear translocation of p53 and p21 and G1/S cell cycle arrest in vitro; increased p53 and 8-oxo-dG levels; and decreased Ki-67 intense/mild staining ratios without TUNEL changes in vivo. These findings suggested that the sensory acceptable doses of PEITC selectively induced ROS-mediated cell cycle arrest leading to delayed tumor progression and extended survival. PEITC could be a functional ingredient for oral cancer prevention.

Taste perception is influenced by several factors. However, the relation between taste perception and food culture is unclear. This study compared taste thresholds between populations with different food culture, i.e. Thai and Japanese. A matched case-control study was conducted in 168 adults (84 for each; aged between 50 and 90 years). The age, sex, systemic disease, medication, smoking, xerostomia, and oral hygiene of both groups were not different. Recognition thresholds (RTs) of sweet, salty, sour, bitter, and umami were measured using filter paper disc (FPD). Detection taste thresholds were measured using electrogustometry. Spicy preference was measured by calibrated questionnaires. Higher RTs of all tastes and higher detection taste thresholds were found in Thai as compared to those of Japanese (P < 0.0001). Separate analyses of healthy and unhealthy persons confirmed the significant differences between 2 countries. The average thresholds for sweet, salty, sour, and bitter in Thai and Japanese were 4 and 2, respectively. The average threshold for umami in Thai and Japanese was 5 and 3, respectively. Moreover, Thai population had stronger preference for spicy food (P < 0.0001) with 70% mild- or moderate and 10% strong lovers, compared to over 90% non- or mild-spicy lovers in Japanese. In addition, 70% of Thai consumed spicy food weekly, whilst 80% of Japanese consumed it monthly. Our findings suggested that population with stronger spicy preference such as Thai had much poorer taste sensitivity and perception than that with milder preference like Japanese. Extensive international survey is needed to conclude the influence of food culture on taste perception., (© The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Determination of bioelement levels in hair is an emerging non-invasive approach for screening bioelement deposition. However, the role of essential bioelement levels in hair and attention deficit/hyperactivity disorder (ADHD) risk or severity is largely unknown. In this study, we have compared multi-element hair profiles between healthy and ADHD Thai children. In addition, the correlations between bioelements and ADHD symptoms according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition, diagnostic criteria were identified. A case-control study was conducted in 111 Thai children (45 newly diagnosed ADHD and 66 matched healthy), aged 3-7 years, living in Bangkok and suburban areas. Levels of 39 bioelements in hair were measured by ICP-MS. Among the analyzed bioelements, Cu/Zn and P/Zn ratios in ADHD children were significantly lower than those in healthy children. Indeed, increased hair Zn level was correlated with more symptoms of inattention, hyperactivity, and total ADHD symptoms. Higher Zn content was also associated with being female and older age. Furthermore, Zn in hair was positively correlated with levels of Ca, Mg, and P; however, it showed a negative correlation with Al, As, Fe, and Mo. These findings warrant further confirmation in a large-scale study. Thai Clinical Trials Registry (TCTR) study ID: 20151113001.

Suitable diet for cancer survivors remains an unresolved challenge. Increased glucose utilization is a hallmark of various cancers. Therefore, alternative carbohydrate supplying normal tissue but retarding cancer growth is needed. This study investigated the effect of sugar alcohols on the proliferation of oral cancer cells compared to nontransformed cells and explored the mechanism. Six oral squamous cell carcinoma (CAL-27, FaDu, SCC4, SCC9, SCC15, and SCC25) and one nontransformed oral keratinocyte (OKF6/TERT2) lines were cultured in media containing 1 mg/ml glucose and 5.8 mg/ml xylitol or sorbitol, yielding equal energy input to control group (4.5 mg/ml glucose). Partial substitution of glucose with sugar alcohols especially xylitol significantly suppressed proliferation of oral cancer but not nontransformed cells. Despite the addition of isocaloric quantities of the sugars, cancer cells exposed to low glucose plus xylitol had retarded ATP generation and decreased activity of phosphofructokinase (PFK), the rate-limiting enzyme in glycolysis. Furthermore, D-xylulose, its key metabolic intermediate, enhanced the anticancer effect of xylitol. These findings suggested a selective anticancer activity of xylitol and the potential mechanism involving inhibition of glucose utilization. Partial substitution of glucose with xylitol may be a proper nutrient for oral cancer survivors, deserving further investigation in animal and clinical settings.

Oral hygiene influences taste, affecting appetite and nutrition in older adults. However, the impact of self-administered tongue brushing on their taste perceptions was unclear. This pilot study (N = 44) was aimed to observe the changes in taste thresholds using Filter Paper Disc after tongue brushing in Thai older adults. Based on the results, continuous tongue brushing for 3 months reduced tongue coat (p < 0.01) and improved subjective taste in 74% of participants. Sweet and salty recognition thresholds were reduced in both anterior and posterior tongue, while sour and bitter thresholds were reduced only in posterior tongue. No changes in umami (savory) were observed. Daily brushing was more effective than weekly brushing in improving the sweet and bitter tastes. The data suggested that tongue brushing could improve perception of multiple tastes and daily tongue brushing was recommended as routine personal care for older adults. This study supports further investigation in a randomized-controlled setting., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Dry mouth is common in elderly patients. However, the use of saliva substitute has been limited due to its inedibility. This study investigated the efficacy of oral moisturizing jelly (OMJ), a novel edible saliva substitute. A pre-post design was conducted in 118 elderly patients diagnosed with hypertension and/or diabetes mellitus. After using OMJ, signs and symptoms of dry mouth were compared with baseline data. The properties of saliva were compared between the OMJ use and non-use periods. The use of OMJ for 2 weeks significantly reduced symptoms of dry mouth, while the use for 1 month reduced the signs of xerostomia, prevented the decline of salivary pH(s) and improved buffering capacities. OMJ was equally effective in patients taking 1 to 2 and 3 to 7 medications. Furthermore, 65% of patients preferred OMJ over a commercial product. OMJ could be new edible saliva substitute for elderly patients suffering from dry mouth. Clinicaltrials.gov ID: NCT02317172., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Eating difficulty is a critical and common problem in head and neck cancer patients undergoing radiotherapy (RT). It leads to poor quality of life and extensive tube feeding use. Nutri-jelly, a food gel with semisolid texture, water-releasing ability, and ready-to-eat by spoon, was recently developed to alleviate the trouble. However, its efficacy was unknown. This study investigated the potential effect of Nutri-jelly on health-related quality of life (HRQOL) and nasogastric tube feeding use., Methods: A prospective quasi-randomized patients-preference controlled trial was conducted in 74 head and neck cancer patients. Subjects in study and control groups (37 each) had similar baseline HRQOL and body mass index and undergone definitive radiotherapy (25-35 RT fractions, 5,000-7,000 cGy). Only study group received a 200-ml box of Nutri-jelly as daily supplement throughout radiotherapy. HRQOL was scored by validated questionnaires. The use of tube feeding was collected from medical records., Results: From 11 to 35 RT fractions, the study group maintained higher overall HRQOL score than that of control group (p < 0.0001). Multiple physiologic and psychological aspects of HRQOL especially swallowing difficulty and overall eating problems were significantly improved in study as compared to control group. Promisingly, the percentage of tube feeding use in study group (13.5 %) was dramatically lower than control group (48.6 %)., Conclusions: Continuous supplementation of Nutri-jelly throughout radiotherapy may improve HRQOL and reduce tube feeding demand in head and neck cancer patients who preferred to take them. Nutri-jelly could be an alternative for head and neck cancer patients who have eating difficulty during radiotherapy.

Tumor microenvironment plays a major role in cancer development. Understanding how the stroma affects epithelial transformation will provide a basis for new preventive strategies. Recent evidence suggests that oxidative stress in stroma may play a role in cancer progression, and loss of p53 function in the stromal cells was associated with poor prognosis and high tumor recurrence. However, the underlying mechanisms remain poorly understood. Here, we investigated the role of p53 loss in fibroblasts in epithelial transformation and the mechanistic involvement of reactive species. Using 3D organotypic culture and other assays, we report that the stroma containing p53-deficient fibroblasts could induce the nontumorigenic epithelial cells of oral and ovarian tissue origins to become invasive through reactive nitrogen species (RNS)-mediated release of the cytokine ICAM1. The p53-deficient fibroblasts have increased RNS production and accumulation of oxidative DNA-damage products associated with specific upregulation of endothelial nitric oxide synthase (eNOS). Suppression of RNS production by siRNA of eNOS or the antioxidant NAC reduced ICAM1 expression and prevented the stroma-mediated epithelial invasion. Our study uncovers the novel mechanism by which redox alteration associated with loss of p53 in stromal fibroblasts functions as a key inducer of epithelial transformation and invasion via RNS-mediated ICAM1 signaling. Thus, the modulation of redox signaling in the microenvironment may serve as a new approach to preventing epithelial transformation and suppressing cancer invasion., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Tissue stromal cells interact with leukaemia cells and profoundly affect their viability and drug sensitivity. Here we show a biochemical mechanism by which bone marrow stromal cells modulate the redox status of chronic lymphocytic leukaemia (CLL) cells and promote cellular survival and drug resistance. Primary CLL cells from patients exhibit a limited ability to transport cystine for glutathione (GSH) synthesis owing to a low expression level of Xc-transporter. In contrast, bone marrow stromal cells effectively import cystine and convert it to cysteine, which is then released into the microenvironment for uptake by CLL cells to promote GSH synthesis. The elevated level of GSH enhances leukaemia cell survival and protects them from drug-induced cytotoxicity. Furthermore, disabling this protective mechanism significantly sensitizes CLL cells to drug treatment in the stromal environment. This stromal-leukaemia interaction is critical for CLL cell survival and represents a key biochemical pathway for effectively targeting leukaemia cells to overcome drug resistance in vivo.

Increased aerobic glycolysis and oxidative stress are important features of cancer cell metabolism, but the underlying biochemical and molecular mechanisms remain elusive. Using a tetracycline inducible model, we show that activation of K-ras(G12V) causes mitochondrial dysfunction, leading to decreased respiration, elevated glycolysis, and increased generation of reactive oxygen species. The K-RAS protein is associated with mitochondria, and induces a rapid suppression of respiratory chain complex-I and a decrease in mitochondrial transmembrane potential by affecting the cyclosporin-sensitive permeability transition pore. Furthermore, pre-induction of K-ras(G12V) expression in vitro to allow metabolic adaptation to high glycolytic metabolism enhances the ability of the transformed cells to form tumor in vivo. Our study suggests that induction of mitochondrial dysfunction is an important mechanism by which K-ras(G12V) causes metabolic changes and ROS stress in cancer cells, and promotes tumor development.

Mitochondria play essential roles in cellular metabolism, redox homeostasis, and regulation of cell death. Emerging evidences suggest that cancer cells exhibit various degrees of mitochondrial dysfunctions and metabolic alterations, which may serve as a basis to develop therapeutic strategies to preferentially kill the malignant cells. Mitochondria as a therapeutic target for cancer treatment is gaining much attention in the recent years, and agents that impact mitochondria with anticancer activity have been identified and tested in vitro and in vivo using various experimental systems. Anticancer agents that directly target mitochondria or indirectly affect mitochondrial functions are collectively classified as mitocans. This review article focuses on several natural compounds that preferentially kill cancer cells with mitochondrial dysfunction, and discusses the possible underlying mechanisms and their therapeutic implications in cancer treatment. Mitocans that have been comprehensively reviewed recently are not included in this article. Important issues such as therapeutic selectivity and the relevant biochemical basis are discussed in the context of future perspectives., (Published by Elsevier B.V.)

Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, and recent studies suggest that this biochemical property of cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumours frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially eliminate these cells by pharmacological ROS insults. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. We argue that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia, and resistance to fludarabine-based therapies is a major challenge in CLL treatment. Because CLL cells are known to have elevated levels of reactive oxygen species (ROS), we aimed to test a novel ROS-mediated strategy to eliminate fludarabine-resistant CLL cells based on this redox alteration. Using primary CLL cells and normal lymphocytes from patients (n = 58) and healthy subjects (n = 12), we showed that both fludarabine-resistant and -sensitive CLL cells were highly sensitive to beta-phenylethyl isothiocyanate (PEITC) with mean IC(50) values of 5.4 microM and 5.1 microM, respectively. Normal lymphocytes were significantly less sensitive to PEITC (IC(50) = 27 microM, P < .001). CLL cells exhibited intrinsically higher ROS level and lower cellular glutathione, which were shown to be the critical determinants of CLL sensitivity to PEITC. Exposure of CLL cells to PEITC induced severe glutathione depletion, ROS accumulation, and oxidation of mitochondrial cardiolipin leading to massive cell death. Such ROS stress also caused deglutathionylation of MCL1, followed by a rapid degradation of this cell survival molecule. Our study demonstrated that the natural compound PEITC is effective in eliminating fludarabine-resistant CLL cells through a redox-mediated mechanism with low toxicity to normal lymphocytes, and warrants further clinical evaluation.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in regulation of cell survival. In general, moderate levels of ROS/RNS may function as signals to promote cell proliferation and survival, whereas severe increase of ROS/RNS can induce cell death. Under physiologic conditions, the balance between generation and elimination of ROS/RNS maintains the proper function of redox-sensitive signaling proteins. Normally, the redox homeostasis ensures that the cells respond properly to endogenous and exogenous stimuli. However, when the redox homeostasis is disturbed, oxidative stress may lead to aberrant cell death and contribute to disease development. This review focuses on the roles of key transcription factors, signal-transduction pathways, and cell-death regulators in affecting cell survival, and how the redox systems regulate the functions of these molecules. The current understanding of how disturbance in redox homeostasis may affect cell death and contribute to the development of diseases such as cancer and degenerative disorders is reviewed. We also discuss how the basic knowledge on redox regulation of cell survival can be used to develop strategies for the treatment or prevention of those diseases.

Cancer cells often exhibit increased reactive oxygen species generation and altered redox regulation. The current study was conducted to investigate the biochemical and molecular events associated with redox alterations during chemical-induced malignant transformation and to evaluate their potential roles in radiation sensitivity. Immortalized nonmalignant human bronchial epithelial cells were exposed to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and a clone of cells exhibiting malignant behaviors was isolated and characterized. This clone initially exhibited an increase in cellular superoxide that eventually decreased after a long-term culture in vitro, associated with altered expression of antioxidant molecules, including an increase in thioredoxin-1 and manganese superoxide dismutase, and a decrease in glutathione peroxidase-1. These cells also showed a significant decrease in sensitivity to ionizing radiation, as demonstrated by less cell death in acute apoptosis analyses and long-term cell proliferation assays. Using biochemical redox modulation and siRNA approach, we showed that the increase in thioredoxin-1 played a significant role in conferring resistance to IR. Although there was a substantial increase in cellular glutathione, inhibition of glutathione synthesis did not increase IR sensitivity. Our study showed complex redox alterations during NNK-induced malignant transformation, and identified Trx-1 as a radiosensitivity modulator.

Reactive oxygen species (ROS) stimulate cell proliferation and induce genetic instability, and their increase in cancer cells is often viewed as an adverse event. Here, we show that such abnormal increases in ROS can be exploited to selectively kill cancer cells using beta-phenylethyl isothiocyanate (PEITC). Oncogenic transformation of ovarian epithelial cells with H-Ras(V12) or expression of Bcr-Abl in hematopoietic cells causes elevated ROS generation and renders the malignant cells highly sensitive to PEITC, which effectively disables the glutathione antioxidant system and causes severe ROS accumulation preferentially in the transformed cells due to their active ROS output. Excessive ROS causes oxidative mitochondrial damage, inactivation of redox-sensitive molecules, and massive cell death. In vivo, PEITC exhibits therapeutic activity and prolongs animal survival.