Exploring the exponential sensitivity of risk perception in the COVID-19 pandemic.

Individual's risk perception regarding specific hazards is a dynamic process that evolves over time. This study analyzed the relationship between the number of COVID-19 cases and the South Korean public's risk perceptions from the outset of the pandemic to the recent past. More than 70 repeated cross-sectional surveys were conducted biweekly to measure individuals' risk perception. An autoregressive integrated moving average with explanatory variable time series analysis was used to characterize the relationship between the number of COVID-19 cases and level of risk perceptions. It revealed that individuals' risk perception and the number of COVID-19 cases were not linearly related but were logarithmically correlated. This finding can be understood as a psychic numbing effect, suggesting that people's perception of risk is not linear but rather exponentially sensitive to changes. The findings also revealed a significant influence of individuals' trust in local governments on their risk perceptions, highlighting the substantial role played by local governments in direct risk management during the COVID-19 pandemic.

Combination therapy of niclosamide with gemcitabine inhibited cell proliferation and apoptosis via Wnt/ß-catenin/c-Myc signaling pathway by inducing ß-catenin ubiquitination in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer with high morbidity and mortality rates worldwide. Owing to a lack of therapeutic options, the overall survival rate of patients with pancreatic cancer is low. Gemcitabine has been mainly used to treat patients with pancreatic cancer, but its efficacy is limited by chemoresistance. Therefore, a novel therapeutic agent for PDAC therapy is urgently needed. An anthelminthic drug, niclosamide, has already been researched in breast, lung, colon, and pancreatic cancer as an anti-cancer purpose by re-positioning its original purpose. However, combination therapy of gemcitabine and niclosamide was not informed yet. Here, we found that niclosamide co-administered with gemcitabine significantly inhibited tumorigenesis of pancreatic cancer compared to gemcitabine alone. Further, combining niclosamide and gemcitabine inhibited cell proliferation and induced apoptosis. Niclosamide induced cell cycle arrest at the G1 phase, and the levels of CDK4/6 and cyclin D1 were lowered after gemcitabine treatment. In addition, the combination of these chemical compounds more effectively increased the binding level of activated ß-catenin destruction complex and ß-catenin to enable phosphorylation, compared to gemcitabine alone. After phosphorylation, niclosamide - gemcitabine upregulated the ubiquitin level, which caused phosphorylated ß-catenin to undergo proteasomal degradation; the combination was more potent than gemcitabine alone. Finally, the combination more effectively suppressed tumor growth in vivo, compared to gemcitabine alone. Altogether, our results indicate that niclosamide synergistically enhances the antitumor effect of gemcitabine in pancreatic cancer, by inducing the degradation of ß-catenin with ubiquitination. Therefore, this drug combination can potentially be used in PDAC therapy.

A simple and efficient cryopreservation method for mouse small intestinal and colon organoids for regenerative medicine.

Organoid cryopreservation method is one of key step in the organoid culture. We aimed to establish a simple and efficient cryopreservation method for mouse small intestinal organoids (MIOs) and colon organoids (MCOs) using various concentrations of cryoprotectant. Based on the theoretical simulation, we optimized the dimethyl sulfoxide (DMSO) concentration by pretreating the organoids with 5, 7.5, and 10% DMSO for 30 min at 4 °C to allow penetration into the organoids and evaluated their viability, proliferation, and function after cryopreservation. Gene expression in the MIOs and staining of lineage markers were examined real-time PCR. The organoids in the DMSO-treated groups as well as the control, expressed ChrgA, Ecad, Muc2, Lyz, villin, and Lgr5, and there are no significant. A forskolin-induced swelling assay for MIOs was performed to confirm normal cystic fibrosis transmembrane conductance regulator (CFTR) activity. Similar forskolin-induced swelling was observed in the DMSO-treated groups and the control. In addition, MCOs were transplanted into mouse colon for confirmation of regeneration therapy efficacy. Thawing organoids were cultured for two and four sequential passages after cryopreservation with 5% DMSO to confirm any changes in the gene expression of lineage markers after subculture. We developed a simple and efficient organoid freezing method using 5% DMSO with low potential toxicity and validated our findings with theoretical simulation.

Recapitulation of First Pass Metabolism Using 3D Printed Microfluidic Chip and Organoid.

The low bioavailability of oral drugs due to first pass metabolism is a major obstacle in drug development. With significant developments in the field of in vitro organ modeling and microfluidic chip three-dimensional (3D) printing, the challenge is to apply these for the production and evaluation of new drug candidates. This study aimed to produce a microfluidic chip to recapitulate and assess the feasibility of the first pass metabolism. The infill condition of the polycarbonate transparent filament and layer height was optimized to visualize and maintain the organoid or spheroid on the chip. Next, the chip was fabricated using a 3D printer after a computer-aided design (CAD). The chip consisted of three wells of different heights. The small intestinal (SI) organoid and colorectal adenocarcinoma spheroids were placed on the second and third wells, respectively. No additional equipment was assembled, and the tilted tunnel was connected to each well to transport the material by gradient force. The chip was fabricated using 50% and 0.1 um thickness. Among the three different prototypes of chip (chips 1, 2, and 3), the highest distribution of plasmids in the Matrigel of the second well was observed in Chip 2 at 48 h. The effect of first pass metabolism was analyzed using docetaxel. In the chip without an SI organoid, there was a marked decrease in the viability of colorectal adenocarcinoma spheroids due to drug efficacy. However, in the chip with the SI organoid, no significant change in viability was observed because of first pass metabolism. In conclusion, we presented a simple, fast, and low-cost microfluidic chip to analyze the efficacy change of candidate drug by the first pass metabolism.

Association between prenatal polycyclic aromatic hydrocarbons and infantile allergic diseases modified by maternal glutathione S-transferase polymorphisms: results from the MOCEH birth cohort.

BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) has been linked to allergic disease onset. Variations in the glutathione S-transferase (GST) gene family can impact the progression of allergic diseases. We sought to examine the association between prenatal PAH exposure and infantile allergic diseases in 6-month-old infants, and how maternal glutathione S-transferase M1 (GSTM1) or T1 (GSTT1) polymorphism affects the association between prenatal PAH exposure and allergic diseases in the Mothers and Children's Environmental Health (MOCEH) study. METHODS: The study sample comprised 349 infants and their mothers from the MOCEH study, for whom 1-hydroxypyrene (1-OHP) and 2-naphthol were measured in both the early period of pregnancy and late period of pregnancy. An infant was deemed to be affected by an allergic disease if diagnosed with or if developed at least one of the allergic diseases. A logistic regression analysis was performed to study the association between urinary 1-OHP and 2-naphthol levels during pregnancy and allergic diseases in 6-month-old infants. Furthermore, analyses stratified by maternal GSTM1 or GSTT1 present/null polymorphisms were performed. RESULTS: The risk of allergic diseases in 6-month-old infants was significantly increased in accordance with an increase in urinary 1-OHP during the early period of pregnancy (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.05, 3.23; by one log-transformed unit of 1-OHP µg/g creatinine). The increased risk of infantile allergic diseases associated with urinary 1-OHP during the early period of pregnancy was limited to the maternal GSTT1 null type (OR: 2.69; 95% CI: 1.17, 6.21, by one log-transformed unit of 1-OHP µg/g creatinine); however, the Relative Excess Risk due to Interaction was not statistically significant. CONCLUSIONS: The present study found that infantile allergic diseases could be affected by intrauterine PAH exposure, particularly in the early prenatal period and the risk was limited to the maternal GSTT1 null type.

Joint association of prenatal bisphenol-A and phthalates exposure with risk of atopic dermatitis in 6-month-old infants.

BACKGROUND: Prenatal exposure to bisphenol A (BPA) and phthalates could trigger immune response. Few studies have investigated the association between prenatal BPA and phthalate exposure and atopic dermatitis (AD) in infants. OBJECTIVE: We aimed to clarify the joint association of prenatal exposure to BPA and phthalate metabolites with AD incidence in 6-month-old infants. METHODS: We included 413 mother-child pairs from the Mothers and Children's Environmental Health (MOCEH) in a prospective birth cohort study. Maternal urinary BPA, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP) concentrations were measured during early and late pregnancy. We applied the Bayesian kernel machine regression (BKMR) with probit regression to estimate the association of BPA and phthalate metabolites with AD incidence after adjusting for potential confounders. Individual association was estimated by differences in predicted probabilities comparing each individual chemical concentration at 75th versus 25th percentiles, while other chemicals were set at their median. Overall joint effect was estimated by differences in predicted probabilities comparing all chemical concentrations at 75th versus 25th percentiles. RESULTS: Individual effect of MEHHP in late pregnancy was strongly associated with incident AD [Difference: 0.244 (95% credible interval: -0.066, 0.554)] in the model including both early and late exposures. Furthermore, we confirmed overall joint association of urinary BPA and phthalate metabolites during pregnancy with a higher risk of AD [0.347 (0.168, 0.526) for late pregnancy exposure, and 0.307 (0.094, 0.521) for both early and late pregnancy]. Additionally, the joint association was more prominent among girls than that in boys. CONCLUSIONS: The joint association of prenatal exposure to BPA and phthalates could be associated with the incident AD in 6-month-old infants. Further studies are needed to confirm the synergistic effect of BPA and phthalate exposures on AD in children.

Cancer cluster among small village residents near the fertilizer plant in Korea.

OBJECTIVES: In Jang-jeom, a small village in Hamra-myeon, Iksan-si, Jeollabuk-do, South Korea, residents raised concerns about a suspected cancer cluster that they attributed to a fertilizer plant near the village. We aimed to investigate whether the cancer incidence in the village was higher than that in the general Korean population when the factory was in operation (2001-2017) and whether living in the village was associated with a higher risk of cancer. METHODS: Using national population data and cancer registration data of South Korea, we estimated the standardized incidence ratios (SIRs) in the village to investigate whether more cancer cases occurred in the village compared to other regions. The SIRs were standardized by age groups of 5 years and sex. In order to investigate whether residence in the village increased the risk of cancer, a retrospective cohort was constructed using National Health Insurance Service (NHIS) databases. We estimated the cancer hazard ratios (HRs) using the Cox proportional hazard model, and defined the exposed area as the village of Jang-jeom, and the unexposed or control area as the village neighborhood in Hamra-myeon. We considered potential confounding variables such as age, sex, and income index in the models. Additionally, we measured polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines (TSNAs), suspected carcinogens that may have caused the cancer cluster, in samples collected from the plant and the village. RESULTS: Twenty-three cancer cases occurred in Jang-jeom from 2001 to 2017. Between 2010 and 2016, the incidence rates of all cancers (SIR: 2.05, except thyroid cancer: 2.22), non-melanoma skin cancer (SIR: 21.14, female: 25.41), and gallbladder (GB) and biliary tract cancer in men (SIR: 16.01) in the village were higher than those in the national population in a way that was statistically significant. In our cohort analysis that included only Hamra-myeon residents who have lived there for more than 7 years, we found a statistically significant increase in the risk of all cancers (HR: 1.99, except thyroid cancer: 2.20), non-melanoma skin cancer (HR: 11.60), GB and biliary tract cancer (HR: 15.24), liver cancer (HR: 6.63), and gastric cancer (HR: 3.29) for Jang-jeom residents compared to other Hamra area residents. We identified PAHs and TSNAs in samples of deposited dust and residual fertilizer from the plant and TSNAs in dust samples from village houses. CONCLUSIONS: The results of the SIR calculation and cancer risk analyses of Jang-jeom village residents from the retrospective cohort design showed consistency in the effect size and direction, suggesting that there was a cancer cluster in Jang-jeom. This study would be a good precedent for cancer cluster investigation.

Determination of polycyclic aromatic hydrocarbons (PAHs) in smoking cessation aids by using high-performance liquid chromatography.

A method has been developed and validated for the determination of polycyclic aromatic hydrocarbons (PAHs) in the electronic liquid/gas (e-liquid/e-gas) of electronic cigarettes (e-cigarettes) and ignitable/non-ignitable smokeless cigarettes by high-performance liquid chromatography-fluorescence detection. The proposed method was further applied to detect the presence of PAHs in 16 commercially available smoking cessation aids. The analytical method for benz [a]anthracene, chrysene, benzo [b]fluoranthene, benzo [k]fluoranthene, benzo [a]pyrene, dibenz [a,h]anthracene, and benzo [g,h,i]perylene (BghiP) was validated in terms of linearity, limit of detection, limit of quantification, recovery (%), accuracy (%), and precision (%). Results showed low levels of PAHs in all samples, except for the non-ignitable cigarettes. In particular, BghiP was detected in e-liquid even though a mixture of food-grade propylene glycol and vegetable glycerin was used, and at least one PAH was present in the e-gas of all e-cigarettes, except for one. From these results, it is necessary to prepare an accurate quantitative analysis method and investigate unexpected hazardous materials generated from smoking cessation aids to prevent health problems and provide the scientific basis for safety management.

CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: multi-institutional case series.

AIM: To report CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease (IgG4-MALT lymphoma), a rare but clinically important complication of ocular adnexal IgG4-related disease. METHODS: We retrospectively reviewed all cases of histologically confirmed ocular adnexal IgG4-related disease at three tertiary and one secondary referral centers, between February 2003 and December 2016. Seven cases of histopathologically diagnosed IgG4-MALT lymphoma were identified. CT and MR images were analyzed by consensus of two experienced head and neck radiologists. RESULTS: Lacrimal glands were the main site of involvement in all seven patients. The lesions typically showed well-demarcated margins, iso- to hyperattenuation on precontrast CT, T2 hypo- to isointensity, T1 isointensity, and homogenous internal architecture with homogenous enhancement pattern. Lesions were mostly hyperdense and isointense to normal extraocular muscles on postcontrast CT and MR images, respectively. CONCLUSION: Unlike in typical ocular adnexal IgG4-related disease, T2 isointensity and hyperattenuation on precontrast CT images were noted in some IgG4-MALT lymphoma cases. Although the findings may be nonspecific, the possibility of accompanying MALT lymphoma may need to be considered, when ocular adnexal lesions in patients clinically suspected of having IgG4-related disease are refractory to glucocorticoids and show T2 isointensity and hyperattenuation on precontrast CT for the optimal management of the patients. However, this is a case series of a very rare complication of ocular adnexal IgG4-related disease, and thus caution is warranted to generalize the conclusion.

Zinc transporter 3 modulates cell proliferation and neuronal differentiation in the adult hippocampus.

The subgranular zone of the dentate gyrus is a subregion of the hippocampus that has two uniquely defining features; it is one of the most active sites of adult neurogenesis as well as the location where the highest concentrations of synaptic zinc are found, the mossy fiber terminals. Therefore, we sought to investigate the idea that vesicular zinc plays a role as a modulator of hippocampal adult neurogenesis. Here, we used ZnT3-/- mice, which are depleted of synaptic-vesicle zinc, to test the effect of targeted deletion of this transporter on adult neurogenesis. We found that this manipulation reduced progenitor cell turnover as well as led to a marked defect in the maturation of newborn cells that survive in the DG toward a neuronal phenotype. We also investigated the effects of zinc (ZnCl2 ), n-acetyl cysteine (NAC), and ZnCl2 plus 2NAC (ZN) supplement on adult hippocampal neurogenesis. Compared with ZnCl2 or NAC, administration of ZN resulted in an increase in proliferation of progenitor cells and neuroblast. ZN also rescued the ZnT3 loss-associated reduction of neurogenesis via elevation of insulin-like growth factor-1 and ERK/CREB activation. Together, these findings reveal that ZnT3 plays a highly important role in maintaining adult hippocampal neurogenesis and supplementation by ZN has a beneficial effect on hippocampal neurogenesis, as well as providing a therapeutic target for enhanced neuroprotection and repair after injury as demonstrated by its ability to prevent aging-dependent cognitive decline in ZnT3-/- mice. Therefore, the present study suggests that ZnT3 and vesicular zinc are essential for adult hippocampal neurogenesis.

Permeability measurement using dynamic susceptibility contrast magnetic resonance imaging enhances differential diagnosis of primary central nervous system lymphoma from glioblastoma.

OBJECTIVES: To test if adding permeability measurement to perfusion obtained from dynamic susceptibility contrast MRI (DSC-MRI) improves diagnostic performance in the differentiation of primary central nervous system lymphoma (PCNSL) from glioblastoma. MATERIALS AND METHODS: DSC-MRI was acquired in 145 patients with pathologically proven glioblastoma (n = 89) or PCNSL (n = 56). The permeability metrics of contrast agent extraction fraction (Ex), apparent permeability (Ka), and leakage-corrected perfusion of normalized cerebral blood volume (nCBVres) and cerebral blood flow (nCBFres) were derived from a tissue residue function. For comparison purposes, the leakage-corrected normalized CBV (nCBV) and relative permeability constant (K2) were also obtained using the established Weisskoff-Boxerman leakage correction method. The area under the receiver operating characteristics curve (AUC) and cross-validation were used to compare the diagnostic performance of the single DSC-MRI parameters with the performance obtained with the addition of permeability metrics. RESULTS: PCNSL demonstrated significantly higher permeability (Ex, p < .001) and lower perfusion (nCBVres, nCBFres, and nCBV, all p < .001) than glioblastoma. The combination of Ex and nCBVres showed the highest performance (AUC, 0.96; 95% confidence interval, 0.92-0.99) for differentiating PCNSL from glioblastoma, which was a significant improvement over the single perfusion (nCBV: AUC, 0.84; nCBVres: AUC, 0.84; nCBFres: AUC, 0.82; all p < .001) or Ex (AUC, 0.80; p < .001) parameters. CONCLUSIONS: Analysis of the combined permeability and perfusion metrics obtained from a single DSC-MRI acquisition improves the diagnostic value for differentiating PCNSL from glioblastoma in comparison with single-parameter nCBV analysis. KEY POINTS: • Permeability measurement can be calculated from DSC-MRI with a tissue residue function-based leakage correction. • Adding Exto CBV aids in the differentiation of PCNSL from glioblastoma. • CBV and Exmeasurements from DSC-MRI were highly reproducible.

Maternal fruit and vegetable or vitamin C consumption during pregnancy is associated with fetal growth and infant growth up to 6 months: results from the Korean Mothers and Children's Environmental Health (MOCEH) cohort study.

BACKGROUND: Based on data obtained from pregnant women who participated in the Mothers and Children's Environmental Health (MOCEH) study in South Korea, we aimed to determine whether maternal intake of fruits and vegetables or vitamin C is associated with fetal and infant growth. METHODS: A total of 1138 Korean pregnant women at 12-28 weeks gestation with their infants were recruited as study participants for the MOCEH. Intake of fruits and vegetables or vitamin C during pregnancy was assessed by a 1-day 24-h recall method. Fetal biometry was determined by ultrasonography at late pregnancy. Infant weight and length were measured at birth and 6 months. RESULTS: A multiple regression analysis after adjusting for covariates showed that maternal intake of fruits and vegetables was positively associated with the biparietal diameter of the fetus and infant's weight from birth to 6 months. Also, maternal vitamin C intake was positively associated with the abdominal circumference of the fetus and infant birth length. In addition, there was a significant inverse relationship between consumption of fruits and vegetables (below the median compared to above the median of ≥519 g/d) and the risk of low growth (<25th percentile) of biparietal diameter (odds ratio (OR): 2.220; 95% confidence interval (CI): 1.153-4.274) and birth weight (OR: 1.434; 95% CI: 1.001-2.056). A significant inverse relationship also existed between vitamin C consumption (below vs above the estimated average requirement (EAR) of ≥85 mg/d) and the risk of low growth (<25th percentile) of birth weight (OR: 1.470; 95% CI: 1.011-2.139), weight from birth to 6 months (OR: 1.520; 95% CI: 1.066-2.165), and length at birth (OR: 1.579; 95% CI: 1.104-2.258). CONCLUSIONS: An increased intake of fruits and vegetables or vitamin C at mid-pregnancy is associated with increased fetal growth and infant growth up to 6 months of age.

Association between phthalate exposure and lower lung function in an urban elderly population: A repeated-measures longitudinal study.

BACKGROUND: Lung function is a major predictor of morbidity and mortality. Only a few studies have explored the association between phthalate exposure and lung function. OBJECTIVE: To evaluate the association between phthalate exposure and lung function in the elderly. METHODS: A total of 3 repeated-measures surveys were conducted in 559 elderly individuals aged ≥60 years in Seoul, Korea, at 1-year intervals (2012-2015). During each survey, urinary mono-(2-ethyl-5-hydrohexyl) phthalate (MEHHP) (geometric mean, 15.68 µg/L), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) (11.97 µg/L), and mono-n-butyl phthalate (MnBP) (2.09 µg/L) levels were measured; moreover, lung function tests and a structured questionnaire interview were performed. We constructed linear mixed models to assess the association between urinary phthalate metabolite levels and lung function. RESULTS: A doubling of creatinine-adjusted urinary phthalate metabolite levels was inversely associated with forced expiratory volume in 1 s (L) (ß = -0.01, 95% confidence interval [CI]: -0.02, 0.004 for MEHHP; ß = -0.02, 95% CI: -0.03, -0.01 for MEOHP; ß = -0.01, 95% CI: -0.03, -0.003 for MnBP) and forced vital capacity (L) (ß = -0.02, 95% CI: -0.03, -0.001 for MEHHP; ß = -0.02, 95% CI: -0.03, -0.004 for MEOHP; ß = -0.02, 95% CI: -0.03, -0.001 for MnBP). A doubling of creatinine-adjusted MnBP levels was associated with increased rates of annual decline in forced vital capacity (L/year) (ß = -0.01, 95% CI: -0.02, -0.001). CONCLUSIONS: Urinary phthalate metabolite levels were associated with lower lung function and an increased rate of decline in lung function in an elderly population.

The cancer chemotherapeutic agent paclitaxel (Taxol) reduces hippocampal neurogenesis via down-regulation of vesicular zinc.

Chemotherapy-induced cognitive impairment (CICI) is increasingly recognized as a major unwanted side effect of an otherwise highly valuable life-saving technology. In part, this awareness is a result of increased cancer survival rates following chemotherapy. Altered hippocampal neurogenesis may play a role in mediating CICI. In particular, zinc could act as a key regulator of this process. To test this hypothesis, we administered paclitaxel (Px) to male C57BL/6 mice for set time periods and then evaluated the effects of Px treatment on hippocampal neurogenesis and vesicular zinc. We found that vesicular zinc levels and expression of zinc transporter 3 (ZnT3) were reduced in Px-treated mice, compared to vehicle-treated mice. Moreover, Px-treated mice demonstrated a significant decrease in the number of neuroblasts present. However, no difference in the number of progenitor cells were observed. In addition, zinc supplementation by treatment with ZnCl2 ameliorated the Px-induced decrease in hippocampal neurogenesis and cognitive impairment. These results suggest that via disruption of vesicular zinc stores in hippocampal mossy fiber terminals, chemotherapy may impinge upon one or more of the sequential stages involved in the maturation of new neurons derived via adult neurogenesis and thereby leads to the progressive cognitive decline associated with CICI.

Vascular and cardiac autonomic function and PM2.5 constituents among the elderly: A longitudinal study.

BACKGROUND: Although epidemiologic studies have shown an association between the total mass of particulate matter <2.5µm in aerodynamic diameter (PM2.5) and cardiovascular disease, few studies have examined PM2.5 constituents associated with vascular and cardiac autonomic dysfunction. METHODS: In this longitudinal study, we investigated the relationship between PM2.5 constituents and blood pressure (BP), and markers of the autonomic nervous system. In 466 elderly subjects residing in communities in Seoul, Korea, we examined 16 constituents, seven sources, and total mass concentrations of PM2.5. We measured the BP, heart rate (HR), and indices of heart rate variability (HRV), such as the standard deviation of normal-to-normal intervals (SDNN), square root of the mean squared differences of successive NN intervals (rMSSD), and two frequency-domain variables (low frequency [LF] and high frequency [HF]). We used linear mixed effects models to assess the association of PM2.5 constituents and sources with cardiovascular markers. RESULTS: BP, HR, and rMSSD were associated with concentration of total mass of PM2.5. For each increase of the interquartile range in PM2.5 constituents, systolic and diastolic BP, and HR increased by 2.1-3.3mmHg, 1.2-2.3mmHg, and 1.2-1.9bpm, respectively, while the rMSSD, LF, and HF decreased by 8.1-9.3%, 16.6%, and 20.4%, respectively. Particularly, elemental carbon, sulfate, ammonium, lead, and strontium in the PM2.5 constituents and emissions from oil combustion and incineration were associated with increased BP, HR, and decreased HRV. CONCLUSIONS: Our results suggest an association between specific PM2.5 constituents and vascular and cardiac autonomic functions. These findings may provide supportive evidence for developing a pollution reduction plan to prevent cardiovascular diseases.

Blood mercury concentrations are associated with decline in liver function in an elderly population: a panel study.

BACKGROUND: Mercury is a toxic heavy metal and is known to affect many diseases. However, few studies have examined the effects of mercury exposure on liver function in the general population. We examined the association between blood mercury concentrations and liver enzyme levels in the elderly. METHODS: We included 560 elderly participants (60 years or older) who were recruited from 2008 to 2010 and followed up to 2014. Subjects visited a community welfare center and underwent a medical examination and measurement of mercury levels up to five times. Analyses using generalized estimating equations model were performed after adjusting for age, sex, education, overweight, alcohol consumption, smoking, regular exercise, high-density lipoproteins cholesterol, and total calorie intake. Additionally, we estimated interaction effects of alcohol consumption with mercury and mediation effect of oxidative stress in the relationship between mercury levels and liver function. RESULTS: The geometric mean (95% confidence interval (CI)) of blood mercury concentrations was 2.81 µg/L (2.73, 2.89). Significant relationships were observed between blood mercury concentrations and the level of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT), after adjusting for potential confounders (P < 0.05). The odds ratios of having abnormal ALT levels were statistically significant in the highest mercury quartile compared to those with the lowest quartile. Particularly, regular alcohol drinkers showed greater effect estimates of mercury on the liver function than non-drinkers groups. There was no mediation effect of oxidative stress in the relationship between blood mercury concentrations and liver function. CONCLUSIONS: Our results suggest that blood mercury levels are associated with elevated liver enzymes and interact with alcohol consumption for the association in the elderly.

Administration of Zinc plus Cyclo-(His-Pro) Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes.

The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro) (ZC) on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ)-induced diabetes. ZC (27 mg/kg) was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase) or 45 (late phase) days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs) and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes.

Zinc plus cyclo-(His-Pro) promotes hippocampal neurogenesis in rats.

Zinc is a central actor in regulating stem cell proliferation and neurogenesis in the adult brain. High levels of vesicular zinc are found in the presynaptic terminals. It has been demonstrated that high levels of vesicular zinc are localized in the presynaptic terminals of the granule cells of the dentate gyrus (DG) and that neurogenesis occurs in the subgranular zone (SGZ). Furthermore, zinc chelation reduces hippocampal neurogenesis in pathological conditions such as hypoglycemia, epilepsy and traumatic brain injury. Here we test the effects of zinc plus cyclo-(His-Pro) (CHP) treatment on neurogenesis in the adult SGZ. In order to increase brain zinc, Sprague-Dawley (SD) rats, aged 5weeks, were given zinc plus CHP (ZC, 27mg/kg) orally available once per day for 2weeks. BrdU was intraperitoneally injected 2 times per day for 4 consecutive days starting 1week after initial ZC treatment. Neurogenesis was analyzed by BrdU, Ki67 and doublecortin (DCX) immunostaining. The number of progenitor cells and immature neurons were significantly increased in the DG following 2weeks of ZC treatment. Hippocampal vesicular zinc content was evaluated with TSQ staining. Vesicular TSQ fluorescent intensity was seen to increase in the mossy fiber area at 2weeks after ZC treatment. The present study demonstrates that zinc supplementation by ZC treatment increases hippocampal neurogenesis and levels of vesicular zinc. These findings provide evidence in support of the essential role of zinc in modulating hippocampal neurogenesis.