Hydroethanolic extract of Cirsium setidens ameliorates doxorubicin-induced cardiotoxicity by AMPK-PGC-1α-SOD-mediated mitochondrial protection.

BACKGROUND: Doxorubicin (DOX) is an effective anticancer agent. However, the clinical outcomes of DOX-based therapies are severely hampered by their significant cardiotoxicity. PURPOSE: We investigated the beneficial effects of an ethanol extract of Cirsium setidens (CSE) on DOX-induced cardiomyotoxicity (DICT). METHODS: UPLC-TQ/MS analysis was used to identify CSE metabolite profiles. H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells were used to evaluate the effects of CSE on DICT-induced cell death. To elucidate the mechanism underlying it, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma co-activator l-alpha (PGC1-α), nuclear respiratory factor 1 (NRF1), NRF2, superoxide dismutase (SOD1), and SOD2 expression was detected using western blot analysis. The oxygen consumption rate (OCR), cellular ROS, and mitochondrial membrane potential were measured. Finally, we confirmed the cardioprotective effect of CSE against DICT in both C57BL/6 mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) by observing various parameters, such as electrophysiological changes, cardiac fibrosis, and cardiac cell death. RESULTS: Chlorogenic acid and nicotiflorin were the major compounds in CSE. Our data demonstrated that CSE blocked DOX-induced cell death of H9c2 cells without hindrance of its apoptotic effects on MDA-MB-231 cells. DOX-induced defects of OCR and mitochondrial membrane potential were recovered in a CSE through upregulation of the AMPK-PGC1-α-NRF1 signaling pathway. CSE accelerated NRF1 translocation to the nucleus, increased SOD activity, and consequently blocked apoptosis in H9c2 cells. In mice treated with 400 mg/kg CSE for 4 weeks, electrocardiogram data, creatine kinase and lactate dehydrogenase levels in the serum, and cardiac fibrosis, were improved. Moreover, various electrophysiological features indicative of cardiac function were significantly enhanced following the CSE treatment of hiPSCCMs. CONCLUSION: Our findings demonstrate CSE that ameliorates DICT by protecting mitochondrial dysfunction via the AMP- PGC1α-NRF1 axis, underscoring the therapeutic potential of CSE and its underlying molecular pathways, setting the stage for future investigations into its clinical applications.

The trend of dental check-up and prevalence of dental complications following the use of bone modifying agents in patients with metastatic breast and prostate cancer: analysis of data from the Korean National Health Insurance Service.

BACKGROUND: Bone-modifying agents (BMA) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMA is associated with dental adverse events (AEs) including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the frequency of dental surveillance before BMA treatment and the prevalence of dental AEs including MRONJ, after BMA treatment in patients with bone metastasis from breast and prostate cancer using data from the national health insurance system. METHODS: Data, including age, cancer diagnosis, administered BMA, and dental AEs during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset. RESULTS: Of the 15,357 patients who received BMA, 1,706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-up increased from 4.4% in 2007 to 16.7% in 2019. Referral to dentists for a dental check-up was more active in clinics/primary hospitals than general/tertiary hospitals, and medical doctors and urologists actively consulted to dentists than general surgeons, regardless of the patient's health insurance status. After BMA treatment, 508 patients (3.8%) developed dental AEs, including abscess (42.9%), acute periodontitis (29.7%), acute pericoronitis (14.9%), and MRONJ (12.5% of dental AEs cases, 0.5% of total BMA treated patients). CONCLUSIONS: Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental management before the initiation of BMA.

Poncirus trifoliata Aqueous Extract Protects Cardiomyocytes against Doxorubicin-Induced Toxicity through Upregulation of NAD(P)H Dehydrogenase Quinone Acceptor Oxidoreductase 1.

Doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, is widely used to treat various types of cancer; however, prolonged treatment induces cardiomyotoxicity. Although studies have been performed to overcome DOX-induced cardiotoxicity (DICT), no effective method is currently available. This study investigated the effects and potential mechanisms of Poncirus trifoliata aqueous extract (PTA) in DICT. Changes in cell survival were assessed in H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells. The C57BL/6 mice were treated with DOX to induce DICT in vivo, and alterations in electrophysiological characteristics, serum biomarkers, and histological features were examined. The PTA treatment inhibited DOX-induced decrease in H9c2 cell viability but did not affect the MDA-MB-231 cell viability. Additionally, the PTA restored the abnormal heart rate, R-R interval, QT interval, and ST segment and inhibited the decrease in serum cardiac and hepatic toxicity indicators in the DICT model. Moreover, the PTA administration protected against myocardial fibrosis and apoptosis in the heart tissue of mice with DICT. PTA treatment restored DOX-induced decrease in the expression of NAD(P)H dehydrogenase quinone acceptor oxidoreductase 1 in a PTA concentration-dependent manner. In conclusion, the PTA inhibitory effect on DICT is attributable to its antioxidant properties, suggesting the potential of PTA as a phytotherapeutic agent for DICT.

An Analysis of John Bowlby's Mourning Stages in Family Art Therapy as a Way to Help the Family Mourning Process.

Purpose: Pediatric palliative care is a rapidly developing multidisciplinary approach that supports children with life-limiting conditions and their families. However, there is limited evidence on how to effectively support bereaved parents and siblings. The purpose of this study is to explore the therapeutic impact of art therapy for bereaved families, in accordance with John Bowlby's four-stage theory of mourning. Methods: This single-case study employed the consensual qualitative research method. Art therapy records of bereaved families were reviewed individually, and records from one case were selected. Verbal statements made during the art therapy sessions and photocopies of the artworks were analyzed to understand the mourning process of the family. Results: A total of 113 statements and 12 artworks from 19 art therapy sessions were analyzed. As the art therapy progressed, each family member exhibited a pattern of engaging in more positive and healthy conversations in daily life, demonstrating the final stage of mourning reorganization and recovery. The family dynamics also revealed that they reconstructed their inner world and redefined the meaning of loss, which is the final stage of mourning. The art therapy provided a safe environment for the family, allowing them to fulfill their wishes and regain the strength needed for recovery. Conclusion: This study suggests that art therapy supports bereaved families in alleviating their psychological difficulties, engaging in a healthy mourning process, and functioning as members of society. Further research is needed to better understand the effect of art therapy as a bereavement support tool in pediatric palliative care.

Effects of school sandplay group therapy on children victims of cyberbullying.

Cyberbullying among children is increasing every year, leading to serious public health problems. Victims suffer serious aftereffects such as depression and suicidal ideation; therefore, early and appropriate psychological intervention and the role of schools are emphasized. This study investigated the effects of school sandplay group therapy (SSGT) on children affected by cyberbullying. This study was designed as a parallel-group non-randomized controlled trial. The study subjects were 139 elementary school students (mean age 11.35 years; standard deviation, 0.479; age range 12-13 years) residing in Cheonan City, Korea, who were assigned to the intervention and comparison groups. The intervention group received 10 sessions of therapy on a weekly basis, for 40 minutes per session. No therapy was administered in the control group. The effectiveness of the intervention was assessed using the Children Depression Inventory, Suicidal Ideation Questionnaire-Junior, and Rosenberg Self-Esteem Scale. The assessment for the comparison group was performed concurrently with that of the intervention group. Data were analyzed using multivariate analysis of variance. In this study, the SSGT group showed a significant decrease in depression and suicidal ideation compared to the control group after sandplay group therapy (SGT), and a significant increase in self-esteem. It was confirmed that SSGT can mitigate the negative consequences of cyberbullying and strengthen protective factors. This suggests that the SSGT can be successfully used for crisis counseling.

In silico identification of molecular mechanisms for stroke risk caused by heavy metals and their mixtures: Sponges and drugs involved.

This study used various approaches and databases to evaluate the molecular processes and identify miRNA sponges and drugs associated with the pathophysiology of stroke caused by heavy metals and their combinations. We found that the genes ALB (albumin), IL1B (Interleukin-1ß), F2 (coagulation factor II), APOA1 (apolipoprotein A1), IL6 (Interleukin 6), and NOS2 (nitric oxide synthase 2) were linked to the development of strokes by 18 chemicals and a combination of cadmium, copper, and lead. These results may point to the significance of detoxification and neuroinflammation in stroke as well as the potential for targeting these genes in future stroke therapies. ALB and IL1B were the most common and significant genes. The "selenium micronutrient network," "vitamin B12 metabolism," and "folate metabolism" were shown to be the most significant pathways connected to the risk of stroke brought on by combined heavy metals. The two main cellular elements that may increase the risk of stroke caused by heavy metals were discovered to be "blood microparticle" and "endoplasmic reticulum lumen." We also observed an important chromosome (chr7p15.3), two transcription factors (NFKB2 [nuclear factor kappa B subunit 2] and NR1I2 [nuclear receptor subfamily 1 group, member 2]), and four microRNAs (hsa-miR-26a-5p, hsa-miR-9-5p, hsa-miR-124-3p, and hsa-miR-155-5p) associated with stroke caused by combined heavy metals. Additionally, for these miRNAs, we created and examined in silico microRNA sponge sequences. Triflusal and andrographolide have been identified as potential treatments for heavy metal-induced stroke. Taken together, heavy metals may be a significant contributor to the pathophysiology of stroke, but further investigation into the precise molecular pathways implicated in stroke pathophysiology is required to corroborate these findings.

Fermented Lettuce Extract Containing Nitric Oxide Metabolites Attenuates Inflammatory Parameters in Model Mice and in Human Fibroblast-Like Synoviocytes.

Lettuce (Lactuca sativa L.) contains various bioactive compounds that can reduce the severity of inflammatory diseases. This study aimed to identify therapeutic effects and underlying mechanisms of fermented lettuce extract (FLE) containing stable nitric oxide (NO) on collagen-induced arthritis (CIA) in mice and fibroblast-like synoviocytes (MH7A line) from patients with rheumatoid arthritis (RA). DBA/1 mice were immunized with bovine type II collagen and orally administered FLE for 14 days. On day 36, mouse sera and ankle joints were collected for serological and histological analysis, respectively. Consuming FLE inhibited RA development, suppressing pro-inflammatory cytokine productions, synovial inflammation, and cartilage degradation. The therapeutic effects of FLE in CIA mice were similar to those of methotrexate (MTX), which is typically used to treat RA. In vitro, FLE suppressed the transforming growth factor-ß (TGF-ß)/Smad signaling pathway in MH7A cells. We also demonstrated that FLE inhibited TGF-ß-induced cell migration, suppressed MMP-2/9 expression, inhibited MH7A cell proliferation, and increased the expression of autophagy markers LC3B and p62 in a dose-dependent manner. Our data suggest that FLE could induce autophagosome formations in the early of stages of autophagy while inhibiting their degradation in the later stages. In conclusion, FLE is a potential therapeutic agent for RA.

Interactions between cadmium, lead, mercury, and arsenic and depression: A molecular mechanism involved.

BACKGROUND: We aimed to assess the interactions between mixed heavy metals, genes, and miRNAs implicated in depression development and to design and create miRNA sponges. METHODS: The key data-mining approaches in this study were the Comparative Toxicogenomics Database (CTD), MIENTURNET, GeneMania, Metascape, Webgestalt, miRNAsong, and Cytoscape software. RESULTS: A mixture of cadmium, lead, mercury, and arsenic was related to the development of depression. Even though the genes acquired from the heavy metals of depression studied were different, the "selenium micronutrient network", "vitamin B12 and folate metabolism", and "positive regulation of peptidyl-serine phosphorylation" pathways were highlighted. The heavy metal mixture altered the genes SOD1, IL6, PTGS2, PON1, BDNF, and ALB, highlighting the role of oxidative stress, pro-inflammatory cytokines, paraoxonase activity, neurotrophic factors, and antioxidants related to depression, as well as the possibility of targeting these genes in prospective depressive treatment. Chr1q31.1, five transcription factors (NR4A3, NR1H4, ATF3, CREB3L3, and NR1I3), the "endoplasmic reticulum lumen," "blood microparticle," and "myelin sheath", were found to be important chromosomal locations, transcription factors, and cellular parts linked to depression and affected by mixed heavy metals. Furthermore, we developed a network-based approach to detect significant genes, miRNA, pathways, and illnesses related to depression development. We also observed eight important miRNAs related to depression induced by mixed heavy metals (hsa-miR-16-5p, hsa-miR-132-3p, hsa-miR-1-3p, hsa-miR-204-5p, hsa-miR-206, hsa-miR-124-3p, hsa-miR-146a-5p, and hsa-miR-26a-5p). In addition, we created and evaluated miRNA sponge sequences for these miRNAs in silico. LIMITATIONS: A toxicogenomic design in silico was used. CONCLUSIONS: Our findings highlight the importance of oxidative stress, notably SOD1 and the selenium micronutrient network, in depression caused by heavy metal mixtures and provide additional insights into common molecular pathways implicated in depression pathogenesis.

UPLC-QTOF-MS-Based Metabolomics and Antioxidant Capacity of Codonopsis lanceolata from Different Geographical Origins.

Codonopsis lanceolata (C. lanceolata) has been commonly utilized as a therapeutic plant in traditional medicine. In this study, we examined variations in metabolites in C. lanceolata roots grown in different regions using ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Multivariate analysis showed that the metabolite profiles of plants grown in Hoengseong and Jeongseon were more similar to each other than to that of C. lanceolata grown in Jeju. Most primary metabolites were present at higher levels in C. lanceolata grown in Jeju. In contrast, C. lanceolata grown in Hoengseong and Jeongseon had high levels of secondary metabolites such as phenylpropanoids and triterpenoid saponins, respectively. In addition, the bioactive compound content and antioxidant capacity of in C. lanceolata grown in Hoengseong and Jeongseon were observed to be higher than those of C. lanceolata grown in Jeju. This study suggests that metabolomics is an effective approach to investigate the difference of metabolite profiling in C. lanceolata from different geographical origins, and is useful for evaluating its pharmacological potential.

Metabolic Profiling of Chestnut Shell (Castanea crenata) Cultivars Using UPLC-QTOF-MS and Their Antioxidant Capacity.

The inner shell of the chestnut (Castanea crenata) has long been used in Asia as a medicinal herb for improving digestion and blood circulation, and treating diarrhea. However, most chestnut shells are now treated as waste materials in industrial peeling processes. In this study, we examined the metabolite variation among major cultivars of C. crenata shells using mass spectrometry. Among five representative cultivars, Okkwang, Porotan, and Ishizuuchi had higher levels of bioactive compounds, such as ellagic acid derivatives, ellagitannins, flavonoids, and gallic acid derivatives. Their antioxidant capacity was positively correlated with their chemical composition. The byproducts (whole shells) from the industrial peeling process were re-evaluated in comparison with the inner shell, a rich source of phenolic compounds. The phenolic acids and flavonoid glucoside derivatives were significantly higher in the whole shells, whereas the levels of flavonoids were higher in the inner shells. In addition, the whole shell extracts significantly reduced cellular reactive oxygen species production compared to the inner shell extracts. This study demonstrated the different biochemical benefits of different C. crenata cultivars through metabolic profiling and suggests that the whole shell could be used as a functional ingredient, as it has the highest levels of bioactive products and antioxidant effects.

Effects of Fermented Garlic Extract Containing Nitric Oxide Metabolites on Blood Flow in Healthy Participants: A Randomized Controlled Trial.

Aged or fermented garlic extract (FGE) is a natural remedy that improves vascular function through increasing vascular nitric oxide (NO) bioavailability. This is because nitrite (NO2-), a NO metabolite, can be produced through bioconversion with macrobacteria during the fermentation of foods like garlic. We aimed to evaluate the effects of NO2- in FGE on blood flow (BF), blood pressure (BP), velocity of the common carotid artery (CCA) and internal carotid artery (ICA), regional cerebral BF (rCBF), and peripheral BF (PBF). The study was divided into two parts: (1) Thirty healthy adults were divided into FGE and placebo groups to compare BP and velocity of the CCA and ICA; and (2) Twenty-eight healthy adults were divided into FGE and placebo groups to compare rCBF and PBF and determine changes before/after ingestion. Significant changes were noted in BP and the velocity of both CCA 30-60 min after FGE ingestion. FGE ingestion resulted in significant increases in rCBF and increases in body surface temperature through alterations in PBF. No detectable clinical side effects were noted. Overall, oral administration of NO2- containing FGE demonstrated acute positive effects in upregulating BF, including the CCA, BP, rCBF, and PBF. Follow-up studies with larger sample sizes and long-term ingestion may be needed.

Evaluation of the Effectiveness of Fermented Soybean-Lettuce Powder for Improving Menopausal Symptoms.

Menopause syndrome causes a decline in the quality of life of postmenopausal women. Hormone therapy is recommended for the treatment of menopausal syndromes. However, it has several side effects. Soybean has been safely used to relieve the symptoms of menopause. Lettuce has antidiabetic and anti-inflammatory effects and improves sleep quality. Natural nitric oxide metabolites are produced through fermentation, which increases the effectiveness of the functional substances. This study assessed the alleviation of menopausal syndrome symptoms by natural nitric oxide-containing soybean lettuce extract using the Kupperman index. This study included adult women with menopausal syndrome and a Kupperman index of ≥15. After a four-week study with 40 participants, the final analysis included 39 participants in the experimental group (n = 19) and the placebo group (n = 20). Body mass index, waist circumference, and the total cholesterol, low-density and high-density lipoprotein cholesterol, and triglyceride levels were not altered before and after treatment in both groups. There was a significant decrease in the Kupperman index after treatment in the experimental group, but no significant change was observed in the placebo group. Soybean lettuce extract alleviates menopause syndrome without any special side effects.

An increased intake of thiamine diminishes the risk of metabolic syndrome in the Korean population with various comorbidities.

BACKGROUND AND AIMS: There is growing evidence that thiamine supplementation could reverse non-communicable diseases such as diabetes and cardiovascular diseases. However, the role of thiamine in metabolic syndrome (MetS) remains unclear. We hypothesized whether an increased intake of thiamine diminishes the risk of MetS in the Korean population with various comorbidities. This study aimed to assess the association between thiamine intake and MetS among adults with comorbidities. METHODS: 57,523 eligible participants aged over 18 years between 2009 and 2019 were recruited to obtain data on sociodemographic characteristics, medical history, current medications, lifestyle, and family history. A 24-h recall was used to determine thiamine intake. Odds ratio (OR) for MetS was calculated for log2-transformed thiamine intake values, subsequently predicting the risk of MetS based on the marginal effect. RESULTS: The risk of MetS was significantly higher in subjects with comorbidities than in those without comorbidities. A doubling of daily thiamine intake was significantly associated with a decrease in MetS among adults with comorbidities by 7% (OR 0.93; 95%CI 0.89-0.97). CONCLUSIONS: The potential health benefits result from the intake of thiamine through an ordinary diet in the clinical management of MetS. Therefore, there is an ongoing need to look into these links between thiamine supplementation and MetS in well-characterized cohorts of participants with comorbidities.

Mixtures modeling identifies vitamin B1 and B3 intakes associated with depression.

BACKGROUND: We aim to identify the association between a mixture of vitamin B1, B2, and B3 intakes and depression. METHODS: Daily intake of vitamins was measured by a one-day 24 h recall. Multivariate logistic regression, weighted quantile sum (WQS), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were used. RESULTS: Of 9,848 adults included in the final analysis, 4.38% had depression. In the logistic regression model, daily vitamin B1 and B3 intakes were associated with depression, and significant trends were observed for these vitamin intake tertiles (p < 0.001). The WQS index was significantly associated with depression (OR = 0.24, 95% CI: 0.23-0.24). The gqcomp index also found a significant association between a mixture of vitamin B1 and B3 intake and depression (OR = 0.67, 95% CI: 0.44-0.98). Vitamin B1 intake was the most heavily weighed vitamin intake in this model. In BKMR analysis, the overall effects of vitamin B1 and B3 intake mixture were negatively associated with depression. Vitamin B1 and B3 intake showed negative trends and was observed as the most important factor associated with depression. The cutoff levels for B vitamin intake levels related to depression were reported. LIMITATIONS: A 24-hour recall and cross-sectional design were used. CONCLUSIONS: Given the rising prevalence of depressive symptoms in Korea, an increase in daily intake of vitamin B1 and/or B3 through regular diets may help to reduce the risk of depression. Therefore, there is an ongoing need to investigate these associations between B vitamin supplementation and depression, either separately or jointly, in well-characterized cohorts of depression population.

Cardiovascular risks associated with calcium supplementation in patients with osteoporosis: a nationwide cohort study.

AIMS: This study aimed to evaluate the real effects of calcium supplementation on cardiovascular outcomes within a population-based cohort. METHODS AND RESULTS: From a nationwide health screening database in South Korea, a total of 11 297 patients with osteoporosis who had taken calcium supplementation with or without vitamin D for at least 90 days [total calcium group; calcium supplementation only (CaO), n = 567; calcium supplementation in combination with vitamin D (CaD), n = 10 730] were matched at a 1:1 ratio to patients who had not taken calcium supplements (control group) by using propensity scores. The overall mean age was 59.9 ± 8.8 years and the percentage of women was 87.9% in our study population. Over a median follow-up of 54 months, the incidence rate of composite cardiovascular diseases (CVDs) per 1000 person-years was not different between the groups: 9.73 in the total calcium group and 8.97 in the control group [adjusted hazard ratio (HR): 1.12; 95% confidence interval (CI): 0.99-1.28; P = 0.08]. However, calcium supplementation without vitamin D was associated with an increased risk of composite CVD (HR: 1.54; 95% CI: 1.17-2.04; P < 0.01), especially non-fatal myocardial infarction (HR: 1.89; 95% CI: 1.23-2.91; P < 0.01), compared with no calcium supplementation. CONCLUSION: Our population-based study supported that taking calcium supplementation combined with vitamin D did not appear to be harmful to cardiovascular health, but reminded that calcium supplementation without vitamin D should be used carefully even in populations with low dietary calcium intake.

Effects of heavy metal, vitamin, and curry consumption on metabolic syndrome during menopause: a Korean community-based cross-sectional study.

OBJECTIVE: To determine the associations between metabolic syndrome (MetS) during menopause and serum heavy metal levels and vitamin and curry consumption. METHODS: A data set of 7,131 pre- and postmenopausal women aged ≥ 20 years collected between 2009 and 2017 was used to obtain information on sociodemographic, lifestyles, family histories, food intakes, and serum heavy metal levels and MetS. Logistic regression was used to identify associations between the presence of MetS and risk factors and to predict risks of MetS based on marginal effects. RESULTS: Our results show that postmenopausal women had a higher risk of MetS than premenopausal women. During postmenopause elevations in the levels of serum cadmium by one unit increased the risk of MetS by 33% (OR 1.33; 95% CI, 1.03-1.72, P = 0.028). Risks of MetS in pre- and postmenopausal women, when serum Hb levels increased by 1 unit increased 21% (OR 1.21; 95% CI, 1.09-1.33, P < 0.001) and 26% (OR 1.26; 95% CI, 1.16-1.38, P < 0.001), respectively. Furthermore, the risk of MetS risk in pre- and postmenopausal women was increased 2.49-fold and 2.79-fold by a 1% increase in HbA1c level (OR 2.49; 95% CI, 1.97-3.16, P < 0.001) and (OR 2.79; 95% CI, 2.30-3.38, P < 0.001), respectively. High curry consumption reduced the risk of MetS significantly more than low curry consumption (OR 0.60; 95% CI, 0.39-0.91, P = 0.017) in premenopausal women. Furthermore, an increase in daily vitamin B2 intake by 1 mg reduced the risk of MetS by 45% (OR 0.55; 95% CI, 0.32-0.94, P = 0.028) in postmenopausal women. CONCLUSION: Vitamin B2 and curry supplementation may protect against MetS. Further work is needed to reduce risk factors associated with heavy metals and determine the effects of vitamins and curry consumption on MetS during menopause.

Video Summary:http://links.lww.com/MENO/A791 .

Association between levels of thiamine intake, diabetes, cardiovascular diseases and depression in Korea: a national cross-sectional study.

The present study aimed to determine thiamine intake levels and the association between thiamine intake, diabetes, cardiovascular diseases and mental health. Participants were interviewed to obtain data on socio-demographic characteristics, lifestyle, current medications, medical and family history. The daily intake of thiamine was assessed by a 24-h recall. The mean age of the 34 700 study subjects was 42⋅9 years (sd 22⋅8, min-max: 1-80) and 19 342 (55⋅7 %) were women. The levels of thiamine intake were 1⋅126 mg (2016), 1⋅115 mg (2017) and 1⋅087 mg (2018) for women, which were equal to or only slightly above the recommended intake of 1⋅10 mg/d for women. The levels of thiamine intake from 2014-15 and 2016-18 significantly decreased. The estimated percentage of insufficient thiamine intake was 37⋅8 % (95 % CI 37⋅3, 38⋅4). Multivariable regression analysis adjusted for potential confounders showed that thiamine intake was critically associated with lower risks of hypertension, MI or angina, type 2 diabetes, depression and dyslipidemia. The daily thiamine intake from food can reversal the risks of hypertension (OR 0⋅95; 95 % CI 0⋅90, 0⋅99), MI or angina (OR 0⋅84; 95 % CI 0⋅74, 0⋅95), type 2 diabetes (OR 0⋅86; 95 % CI 0⋅81, 0⋅93), depression (OR 0⋅90; 95 % CI 0⋅83, 0⋅97) and dyslipidemia (OR 0⋅90; 95 % CI 0⋅86, 0⋅95), respectively. Further works are needed to identify the effects of thiamine and non-communicable diseases (NCDs) and mental health. A preventive thiamine supplementation strategy should be adopted to target NCDs and mental health and risk factors associated with thiamine deficiency. The optimisation of NCD control and mental health protection is also a vital integral part of Korea's public health system.

N,N'-Diacetyl-p-phenylenediamine restores microglial phagocytosis and improves cognitive defects in Alzheimer's disease transgenic mice.

As a central feature of neuroinflammation, microglial dysfunction has been increasingly considered a causative factor of neurodegeneration implicating an intertwined pathology with amyloidogenic proteins. Herein, we report the smallest synthetic molecule (N,N'-diacetyl-p-phenylenediamine [DAPPD]), simply composed of a benzene ring with 2 acetamide groups at the para position, known to date as a chemical reagent that is able to promote the phagocytic aptitude of microglia and subsequently ameliorate cognitive defects. Based on our mechanistic investigations in vitro and in vivo, 1) the capability of DAPPD to restore microglial phagocytosis is responsible for diminishing the accumulation of amyloid-ß (Aß) species and significantly improving cognitive function in the brains of 2 types of Alzheimer's disease (AD) transgenic mice, and 2) the rectification of microglial function by DAPPD is a result of its ability to suppress the expression of NLRP3 inflammasome-associated proteins through its impact on the NF-κB pathway. Overall, our in vitro and in vivo investigations on efficacies and molecular-level mechanisms demonstrate the ability of DAPPD to regulate microglial function, suppress neuroinflammation, foster cerebral Aß clearance, and attenuate cognitive deficits in AD transgenic mouse models. Discovery of such antineuroinflammatory compounds signifies the potential in discovering effective therapeutic molecules against AD-associated neurodegeneration.

Metabolic Alterations in Two Cirsium Species Identified at Distinct Phenological Stages using UPLC-QTOF/MS.

INTRODUCTION: Cirsium chanroenicum and C. setidens are commonly used both in traditional folk medicine and as a food source. The quality of different species of Cirsium at different harvest times is a function of their metabolite composition, which is determined by the phenological stage. OBJECTIVE: We sought to determine the differences in the metabolite composition of two species of Cirsium during different phenological stages using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight (QTOF) mass spectrometry (MS). METHODOLOGY: Cirsium chanroenicum and C. setidens plants were collected at the floral budding and full flowering stages. Metabolic profiles of Cirsium extracts were determined using UPLC-QTOF/MS to characterise the differences between phenological stages, and the major metabolites were quantified using UPLC-QTOF/MS-multiple reaction monitoring (MRM). RESULTS: At the full flowering stage, the levels of phenolic acids as well as components of the phenylpropanoid pathway were increased. Flavonoids predominated at the full flowering stage in both species. The levels of coumaric acid, kaempferol, and pectolinarigenin differed between the two species of Cirsium. Overall, these results suggest that components of the phenylpropanoid metabolic pathway are upregulated in the full flowering stage in Cirsium, although we did observe some variation between the species. CONCLUSION: These results will help elucidate the metabolic pathways related to the different phases of the vegetative cycle, and may help determine the optimal season for the harvest of Cirsium with the highest levels of bioactive compounds. Copyright © 2017 John Wiley & Sons, Ltd.