Short-term ozone exposure and cancer mortality in Brazil: A nationwide case-crossover study.

Exposure to ambient ozone (O3) is linked to increased mortality risks from various diseases, but epidemiological investigations delving into its potential implications for cancer mortality are limited. We aimed to examine the association between short-term O3 exposure and site-specific cancer mortality and investigate vulnerable subgroups in Brazil. In total 3,459,826 cancer death records from 5570 Brazilian municipalities between 2000 and 2019, were included. Municipal average daily O3 concentration was calculated from a global estimation at 0.25°×0.25° spatial resolution. The time-stratified case-crossover design was applied to assess the O3-cancer mortality association. Subgroup analyses by age, sex, season, time-period, region, urban hierarchy, climate classification, quantiles of GDP per capita and illiteracy rates were performed. A linear and non-threshold exposure-response relationship was observed for short-term exposure to O3 with cancer mortality, with a 1.00% (95% CI: 0.79%-1.20%) increase in all-cancer mortality risks for each 10-µg/m3 increment of three-day average O3. Kidney cancer was most strongly with O3 exposure, followed by cancers of the prostate, stomach, breast, lymphoma, brain and lung. The associated cancer risks were relatively higher in the warm season and in southern Brazil, with a decreasing trend over time. When restricting O3 concentration to the national minimum value during 2000-2019, a total of 147,074 (116,690-177,451) cancer deaths could be avoided in Brazil, which included 17,836 (7014-28,653) lung cancer deaths. Notably, these associations persisted despite observed adaptation within the Brazilian population, highlighting the need for a focus on incorporating specific measures to mitigate O3 exposure into cancer care recommendations.

Cancer mortality risk from short-term PM2.5 exposure and temporal variations in Brazil.

Although some studies have found that short-term PM2.5 exposure is associated with lung cancer deaths, its impact on other cancer sites is unclear. To answer this research question, this time-stratified case-crossover study used individual cancer death data between January 1, 2000, and December 31, 2019, extracted from the Brazilian mortality information system to quantify the associations between short-term PM2.5 exposure and cancer mortality from 25 common cancer sites. Daily PM2.5 concentration was aggregated at the municipality level as the key exposure. The study included a total of 34,516,120 individual death records, with the national daily mean PM2.5 exposure 15.3 (SD 4.3) µg/m3. For every 10-µg/m3 increase in three-day average PM2.5 exposure, the odds ratio (OR) for all-cancer mortality was 1.04 (95% CI 1.03-1.04). Apart from all-cancer deaths, PM2.5 exposure may impact cancers of oesophagus (1.04, 1.00-1.08), stomach (1.05, 1.02-1.08), colon-rectum (1.04, 1.01-1.06), lung (1.04, 1.02-1.06), breast (1.03, 1.00-1.06), prostate (1.07, 1.04-1.10), and leukaemia (1.05, 1.01-1.09). During the study period, acute PM2.5 exposure contributed to an estimated 1,917,994 cancer deaths, ranging from 0 to 6,054 cases in each municipality. Though there has been a consistent downward trend in PM2.5-related all-cancer mortality risks from 2000 to 2019, the impact remains significant, indicating the continued importance of cancer patients avoiding PM2.5 exposure. This nationwide study revealed a notable association between acute PM2.5 exposure and heightened overall and site-specific cancer mortality for the first time to our best knowledge. The findings suggest the importance of considering strategies to minimize such exposure in cancer care guidelines. ENVIRONMENTAL IMPLICATION: The 20-year analysis of nationwide death records in Brazil revealed that heightened short-term exposure to PM2.5 is associated with increased cancer mortality at various sites, although this association has gradually decreased over time. Despite the declining impact, the research highlights the persistent adverse effects of PM2.5 on cancer mortality, emphasizing the importance of continued research and preventive measures to address the ongoing public health challenges posed by air pollution.

Wildfire-related PM2.5 and cardiovascular mortality: A difference-in-differences analysis in Brazil.

Brazil has experienced unprecedented wildfires recently. We aimed to investigate the association of wildfire-related fine particulate matter (PM2.5) with cause-specific cardiovascular mortality, and to estimate the attributable mortality burden. Exposure to wildfire-related PM2.5 was defined as exposure to annual mean wildfire-related PM2.5 concentrations in the 1-year prior to death. The variant difference-in-differences method was employed to explore the wildfire-related PM2.5-cardiovascular mortality association. We found that, in Brazil, compared with the population in the first quartile (Q1: ≤1.82 µg/m3) of wildfire-related PM2.5 exposure, those in the fourth quartile (Q4: 4.22-17.12 µg/m3) of wildfire-related PM2.5 exposure had a 2.2% (RR: 1.022, 95% CI: 1.013-1.032) higher risk for total cardiovascular mortality, 3.1% (RR: 1.031, 95% CI: 1.014-1.048) for ischaemic heart disease mortality, and 2.0% (RR: 1.020, 95% CI: 1.002-1.038) for stroke mortality. From 2010 to 2018, an estimation of 35,847 (95% CI: 22,424-49,177) cardiovascular deaths, representing 17.77 (95% CI: 11.12-24.38) per 100,000 population, were attributable to wildfire-related PM2.5 exposure. Targeted health promotion strategies should be developed for local governments to protect the public from the risk of wildfire-related cardiovascular premature deaths.

Ambient PM2.5 and productivity-adjusted life years lost in Brazil: a national population-based study.

Enormous health burden has been associated with air pollution and its effects continue to grow. However, the impact of air pollution on labour productivity at the population level is still unknown. This study assessed the association between premature death due to PM2.5 exposure and the loss of productivity-adjusted life years (PALYs), in Brazil. We applied a novel variant of the difference-in-difference (DID) approach to assess the association. Daily all-cause mortality data in Brazil were collected from 2000-2019. The PALYs lost increased by 5.11% (95% CI: 4.10-6.13%), for every 10 µg/m3 increase in the 2-day moving average of PM2.5. A total of 9,219,995 (95% CI: 7,491,634-10,921,141) PALYs lost and US$ 268.05 (95% CI: 217.82-317.50) billion economic costs were attributed to PM2.5 exposure, corresponding to 7.37% (95% CI: 5.99-8.73%) of the total PALYs lost due to premature death. This study also found that 5,005,306 PALYs could be avoided if the World Health Organization (WHO) air quality guideline (AQG) level was met. In conclusion, this study demonstrates that ambient PM2.5 exposure is associated with a considerable labour productivity burden relating to premature death in Brazil, while over half of the burden could be prevented if the WHO AQG was met. The findings highlight the need to reduce ambient PM2.5 levels and provide strong evidence for the development of strategies to mitigate the economic impacts of air pollution.

Tropical cyclone-specific mortality risks and the periods of concern: A multicountry time-series study.

BACKGROUND: More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale. METHODS AND FINDINGS: Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan. CONCLUSIONS: The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability.

Wildfire-related PM2.5 and health economic loss of mortality in Brazil.

BACKGROUND: Wildfire imposes a high mortality burden on Brazil. However, there is a limited assessment of the health economic losses attributable to wildfire-related fine particulate matter (PM2.5). METHODS: We collected daily time-series data on all-cause, cardiovascular, and respiratory mortality from 510 immediate regions in Brazil during 2000-2016. The chemical transport model GEOS-Chem driven with Global Fire Emissions Database (GFED), in combination with ground monitored data and machine learning was used to estimate wildfire-related PM2.5 data at a resolution of 0.25°â€ˆ× 0.25°. A time-series design was applied in each immediate region to assess the association between economic losses due to mortality and wildfire-related PM2.5 and the estimates were pooled at the national level using a random-effect meta-analysis. We used a meta-regression model to explore the modification effect of GDP and its sectors (agriculture, industry, and service) on economic losses. RESULTS: During 2000-2016, a total of US$81.08 billion economic losses (US$5.07 billion per year) due to mortality were attributable to wildfire-related PM2.5 in Brazil, accounting for 0.68% of economic losses and equivalent to approximately 0.14% of Brazil's GDP. The attributable fraction (AF) of economic losses due to wildfire-related PM2.5 was positively associated with the proportion of GDP from agriculture, while negatively associated with the proportion of GDP from service. CONCLUSION: Substantial economic losses due to mortality were associated with wildfires, which could be influenced by the agriculture and services share of GDP per capita. Our estimates of the economic losses of mortality could be used to determine optimal levels of investment and resources to mitigate the adverse health impacts of wildfires.

Productivity-adjusted life years lost due to non-optimum temperatures in Brazil: A nationwide time-series study.

Non-optimal temperatures are associated with premature deaths globally. However, the evidence is limited in low- and middle-income countries, and the productivity losses due to non-optimal temperatures have not been quantified. We aimed to estimate the work-related impacts and economic losses attributable to non-optimal temperatures in Brazil. We collected daily mortality data from 510 immediate regions in Brazil during 2000 and 2019. A two-stage time-series analysis was applied to evaluate the association between non-optimum temperatures and the Productivity-Adjusted Life-Years (PALYs) lost. The temperature-PALYs association was fitted for each location in the first stage and then we applied meta-analyses to obtain the national estimations. The attributable fraction (AF) of PALY lost due to ambient temperatures and the corresponding economic costs were calculated for different subgroups of the working-age population. A total of 3,629,661 of PALYs lost were attributed to non-optimal temperatures during 2000-2019 in Brazil, corresponding to 2.90 % (95 % CI: 1.82 %, 3.95 %) of the total PALYs lost. Non-optimal temperatures have led to US$104.86 billion (95 % CI: 65.95, 142.70) of economic costs related to PALYs lost and the economic burden was more substantial in males and the population aged 15-44 years. Higher risks of extreme cold temperatures were observed in the South region in Brazil while extreme hot temperatures were observed in the Central West and Northeast regions. In conclusion, non-optimal temperatures are associated with considerable labour losses as well as economic costs in Brazil. Tailored policies and adaptation strategies should be proposed to mitigate the impacts of non-optimal temperatures on the labour supply in a changing climate.

Short-term exposure to wildfire-related PM2.5 increases mortality risks and burdens in Brazil.

To assess mortality risks and burdens associated with short-term exposure to wildfire-related fine particulate matter with diameter ≤ 2.5 µm (PM2.5), we collect daily mortality data from 2000 to 2016 for 510 immediate regions in Brazil, the most wildfire-prone area. We integrate data from multiple sources with a chemical transport model at the global scale to isolate daily concentrations of wildfire-related PM2.5 at a 0.25 × 0.25 resolution. With a two-stage time-series approach, we estimate (i) an increase of 3.1% (95% confidence interval [CI]: 2.4, 3.9%) in all-cause mortality, 2.6% (95%CI: 1.5, 3.8%) in cardiovascular mortality, and 7.7% (95%CI: 5.9, 9.5) in respiratory mortality over 0-14 days with each 10 µg/m3 increase in daily wildfire-related PM2.5; (ii) 0.65% of all-cause, 0.56% of cardiovascular, and 1.60% of respiratory mortality attributable to acute exposure to wildfire-related PM2.5, corresponding to 121,351 all-cause deaths, 29,510 cardiovascular deaths, and 31,287 respiratory deaths during the study period. In this study, we find stronger associations in females and adults aged ≥ 60 years, and geographic difference in the mortality risks and burdens.

Exposure to wildfire-related PM2.5 and site-specific cancer mortality in Brazil from 2010 to 2016: A retrospective study.

BACKGROUND: Long-term exposure to fine particles ≤2.5 µm in diameter (PM2.5) has been linked to cancer mortality. However, the effect of wildfire-related PM2.5 exposure on cancer mortality risk is unknown. This study evaluates the association between wildfire-related PM2.5 and site-specific cancer mortality in Brazil, from 2010 to 2016. METHODS AND FINDINGS: Nationwide cancer death records were collected during 2010-2016 from the Brazilian Mortality Information System. Death records were linked with municipal-level wildfire- and non-wildfire-related PM2.5 concentrations, at a resolution of 2.0° latitude by 2.5° longitude. We applied a variant difference-in-differences approach with quasi-Poisson regression, adjusting for seasonal temperature and gross domestic product (GDP) per capita. Relative risks (RRs) and 95% confidence intervals (CIs) for the exposure for specific cancer sites were estimated. Attributable fractions and cancer deaths were also calculated. In total, 1,332,526 adult cancer deaths (age ≥ 20 years), from 5,565 Brazilian municipalities, covering 136 million adults were included. The mean annual wildfire-related PM2.5 concentration was 2.38 µg/m3, and the annual non-wildfire-related PM2.5 concentration was 8.20 µg/m3. The RR for mortality from all cancers was 1.02 (95% CI 1.01-1.03, p < 0.001) per 1-µg/m3 increase of wildfire-related PM2.5 concentration, which was higher than the RR per 1-µg/m3 increase of non-wildfire-related PM2.5 (1.01 [95% CI 1.00-1.01], p = 0.007, with p for difference = 0.003). Wildfire-related PM2.5 was associated with mortality from cancers of the nasopharynx (1.10 [95% CI 1.04-1.16], p = 0.002), esophagus (1.05 [95% CI 1.01-1.08], p = 0.012), stomach (1.03 [95% CI 1.01-1.06], p = 0.017), colon/rectum (1.08 [95% CI 1.05-1.11], p < 0.001), larynx (1.06 [95% CI 1.02-1.11], p = 0.003), skin (1.06 [95% CI 1.00-1.12], p = 0.003), breast (1.04 [95% CI 1.01-1.06], p = 0.007), prostate (1.03 [95% CI 1.01-1.06], p = 0.019), and testis (1.10 [95% CI 1.03-1.17], p = 0.002). For all cancers combined, the attributable deaths were 37 per 100,000 population and ranged from 18/100,000 in the Northeast Region of Brazil to 71/100,000 in the Central-West Region. Study limitations included a potential lack of assessment of the joint effects of gaseous pollutants, an inability to capture the migration of residents, and an inability to adjust for some potential confounders. CONCLUSIONS: Exposure to wildfire-related PM2.5 can increase the risks of cancer mortality for many cancer sites, and the effect for wildfire-related PM2.5 was higher than for PM2.5 from non-wildfire sources.

Loss of life expectancy from PM2.5 in Brazil: A national study from 2010 to 2018.

BACKGROUND: Long-term exposure to PM2.5 is proved to be linked with mortality. However, limited studies have estimated the PM2.5 related loss of life expectancy (LLE) and its changing trends. How much life expectancy would be improved if PM2.5 pollution is reduced to the new WHO air quality guideline (AQG) level is unclear. METHODS: Data on deaths from all-causes, cancer, cardiovascular and respiratory diseases were collected from 5,565 Brazilian municipalities during 2010-2018. A difference-in-differences approach with quasi-Poisson regression was applied to examine the PM2.5-years of life lost (YLL) associations and PM2.5 associated LLE. RESULTS: The annual PM2.5 concentration in each municipality from 2010 to 2018 was 7.7 µg/m3 in Brazil. Nationally, with each 10 µg/m3 increase in five-year-average (current and previous four years) concentrations of PM2.5, the relative risks (RRs) were 1.18 (95% CI: 1.15-1.21) for YLL from all-causes, 1.22 (1.16-1.28) from cancer, 1.12 (1.08-1.17) from cardiovascular and 1.17 (1.10-1.25) from respiratory diseases. Life expectancy could be improved by 1.09 (95% CI: 0.92-1.25) years by limiting PM2.5 concentration to the national lowest level (2.9 µg/m3), specifically, 0.20 (0.15-0.24) years for cancer, 0.16 (0.11-0.22) years for cardiovascular and 0.09 (0.05-0.13) years for respiratory diseases, with significant disparities across regions and municipalities. Life expectancy would be improved by 0.78 (0.66-0.90) years by setting the new WHO AQG PM2.5 concentration level of 5 µg/m3 as an acceptable threshold. CONCLUSIONS: Using nationwide death records in Brazil, we found that long-term exposure to PM2.5 was associated with reduced life expectancy from all-causes, cancer, cardiovascular and respiratory diseases with regional inequalities and different trends. PM2.5 pollution abatement to below the WHO AQG level would improve this loss of life expectancy in Brazil.

Associations between long-term exposure to PM2.5 and site-specific cancer mortality: A nationwide study in Brazil between 2010 and 2018.

Long-term exposure to PM2.5 has been linked to lung cancer incidence and mortality, but limited evidence existed for other cancers. This study aimed to assess the association between PM2.5 on cancer specific mortality. An ecological study based on the cancer mortality data collected from 5,565 Brazilian cities during 2010-2018 using a difference-in-differences approach with quasi-Poisson regression, was applied to examine PM2.5-cancer mortality associations. Globally gridded annual average surface PM2.5 concentration was extracted and linked with the residential municipality of participants in this study. Sex, age stratified and exposure-response estimations were also conducted. Totalling 1,768,668 adult cancer deaths records of about 208 million population living across 5,565 municipalities were included in this study. The average PM2.5 concentration was 7.63 µg/m3 (standard deviation 3.32) with range from 2.95 µg/m3 to 28.5 µg/m3. With each 10 µg/m3 increase in three-year-average (current year and previous two years) concentrations of PM2.5, the relative risks (RR) of cancer mortality were 1.16 (95% confidence interval [CI]: 1.11-1.20) for all-site cancers. The PM2.5 exposure was significantly associated with several cancer-specific mortalities including oral, nasopharynx, oesophagus, and stomach, colon rectum, liver, gallbladder, larynx, lung, bone, skin, female breast, cervix, prostate, brain and leukaemia. No safe level of PM2.5 exposure was observed in the exposure-response curve for all types of cancer. In conclusion, with nationwide cancer death records in Brazil, we found that long-term exposure to ambient PM2.5 increased risks of mortality for many cancer types. Even low level PM2.5 concentrations had significant impacts on cancer mortality.

Draft Genome Sequence and De Novo Assembly of a Fusarium oxysporum f. sp. lycopersici Isolate Collected from the Andean Region in Colombia.

We report a draft genome assembly of the causal agent of tomato vascular wilt, Fusarium oxysporum f. sp. lycopersici isolate 59, obtained from the Andean region in Colombia.

The impacts of long-term exposure to PM2.5 on cancer hospitalizations in Brazil.

BACKGROUND: Long-term exposure to PM2.5 has been linked to cancer incidence and mortality. However, it was unknown whether there was an association with cancer hospitalizations. METHODS: Data on cancer hospitalizations and annual PM2.5 concentrations were collected from 1,814 Brazilian cities during 2002-2015. A difference-in-difference approach with quasi-Poisson regression was applied to examine State-specific associations. The State-specific associations were pooled at a national level using random-effect meta-analyses. PM2.5 attributable burden were estimated for cancer hospitalization admissions, inpatient days and costs. RESULTS: We included 5,102,358 cancer hospitalizations (53.8% female). The mean annual concentration of PM2.5 was 7.0 µg/m3 (standard deviation: 4.0 µg/m3). With each 1 µg/m3 increase in two-year-average (current year and previous one year) concentrations of PM2.5, the relative risks (RR) of hospitalization were 1.04 (95% confidence interval [CI]: 1.02 to 1.07) for all-site cancers from 2002 to 2015 without sex and age differences. We estimated that 33.82% (95%CI: 14.97% to 47.84%) of total cancer hospitalizations could be attributed to PM2.5 exposure in Brazil during the study time. For every 100,000 population, 1,190 (95%CI: 527 to 1,836) cancer hospitalizations, 8,191 (95%CI: 3,627 to 11,587) inpatient days and US$788,775 (95%CI: $349,272 to $1,115,825) cost were attributable to PM2.5 exposure. CONCLUSIONS: Long-term exposure to ambient PM2.5 was positively associated with hospitalization for many cancer types in Brazil. Inpatient days and cost would be saved if the annual PM2.5 exposure was reduced.

Cytidine-phosphate-guanosine oligodeoxynucleotides in combination with CD40 ligand decrease periodontal inflammation and alveolar bone loss in a TLR9-independent manner.

Local administration of toll-like receptor 9 (TLR9), agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG ODNs), and CD40 ligand (CD40L) can decrease ligature-induced periodontal inflammation and bone loss in wild type (WT) mouse. OBJECTIVE: This study aimed to explore whether such effect is dependent on TLR9 signaling. MATERIAL AND METHODS: Purified spleen B cells isolated from WT C57BL/6J mice and TLR9 knockout (KO) mice were cultured for 48 hours under the following conditions: CD40L, CpG+CD40L, CpG at low, medium and high doses. We determined B cell numbers using a hemocytometer at 24 h and 48 h. Percentages of CD1dhiCD5+ B cells were detected by flow cytometry. Interleukin-10 (IL-10) mRNA expression and protein secretion were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and by ELISA, respectively. The silk ligature was tied around the maxillary second molars for 14 days, during which the CpG+CD40L mixture or PBS was injected into palatal gingiva on days 3, 6, and 9. RESULTS: For both WT and TLR9 KO mice, CpG significantly induced B cell proliferation, increased IL-10 mRNA expression and protein secretion of IL-10 but reduced CD1dhiCD5+ B cells population; local injection of CpG+CD40L mixture significantly decreased alveolar bone loss and the number of TRAP-positive cells adjacent to the alveolar bone surface, and significantly increased the gingival mRNA expression of IL-10 and decreased RANKL and IFN-γ mRNA expression. CONCLUSIONS: These results indicated that CpG plus CD40L decreased periodontal inflammation and alveolar bone loss in a TLR9-independent manner in ligature-induced experimental periodontitis.

Cytidine-phosphate-guanosine oligodeoxynucleotides in combination with CD40 ligand decrease periodontal inflammation and alveolar bone loss in a TLR9-independent manner

Abstract Local administration of toll-like receptor 9 (TLR9), agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG ODNs), and CD40 ligand (CD40L) can decrease ligature-induced periodontal inflammation and bone loss in wild type (WT) mouse. Objective: This study aimed to explore whether such effect is dependent on TLR9 signaling. Material and Methods: Purified spleen B cells isolated from WT C57BL/6J mice and TLR9 knockout (KO) mice were cultured for 48 hours under the following conditions: CD40L, CpG+CD40L, CpG at low, medium and high doses. We determined B cell numbers using a hemocytometer at 24 h and 48 h. Percentages of CD1dhiCD5+ B cells were detected by flow cytometry. Interleukin-10 (IL-10) mRNA expression and protein secretion were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and by ELISA, respectively. The silk ligature was tied around the maxillary second molars for 14 days, during which the CpG+CD40L mixture or PBS was injected into palatal gingiva on days 3, 6, and 9. Results: For both WT and TLR9 KO mice, CpG significantly induced B cell proliferation, increased IL-10 mRNA expression and protein secretion of IL-10 but reduced CD1dhiCD5+ B cells population; local injection of CpG+CD40L mixture significantly decreased alveolar bone loss and the number of TRAP-positive cells adjacent to the alveolar bone surface, and significantly increased the gingival mRNA expression of IL-10 and decreased RANKL and IFN-γ mRNA expression. Conclusions: These results indicated that CpG plus CD40L decreased periodontal inflammation and alveolar bone loss in a TLR9-independent manner in ligature-induced experimental periodontitis.

Toll-like receptor agonists Porphyromonas gingivalis LPS and CpG differentially regulate IL-10 competency and frequencies of mouse B10 cells.

OBJECTIVE: This study is to determine the effects of P. gingivalis LPS and CpG on B10 cell expansion and IL-10 competency in vitro. MATERIAL AND METHODS: Spleen B cells were isolated from C57BL/6J mice with or without formalin-fixed P. gingivalis immunization. B cells were cultured for 48 hours under the following conditions: CD40L, CD40L+LPS, CD40L+CpG, and CD40L+LPS+CpG in the presence or absence of fixed P. gingivalis. Percentages of CD1dhiCD5+ B cells were measured by flow cytometry. IL-10 mRNA expression and secreted IL-10 were measured by real-time quantitative PCR and by ELISA respectively. RESULTS: P. gingivalis LPS plus CD40L significantly increased CD1dhiCD5+ B cell percentages and secreted IL-10 levels in both immunized and non-immunized mice B cells in the presence or absence of P. gingivalis, compared with control group. Secreted IL-10 levels were significantly increased in CD40L+LPS treated group compared with CD40L treatment group in the absence of P. gingivalis. CpG plus CD40L significantly decreased CD1dhiCD5+ B cell percentages, but greatly elevated secreted IL-10 levels in immunized and non-immunized mice B cells in the absence of P. gingivalis, compared with CD40L treatment group. CONCLUSIONS: P. gingivalis LPS and CpG differentially enhance IL-10 secretion and expansion of mouse B10 cells during innate and adaptive immune responses.

Toll-like receptor agonists Porphyromonas gingivalis LPS and CpG differentially regulate IL-10 competency and frequencies of mouse B10 cells

Abstract IL-10 expressing regulatory B cells (B10) play a key role in immune system balance by limiting excessive inflammatory responses. Effects of toll-like receptor signaling and co-stimulatory molecules on B10 activity during innate and adaptive immune responses are not fully understood. Objective This study is to determine the effects of P. gingivalis LPS and CpG on B10 cell expansion and IL-10 competency in vitro. Material and Methods Spleen B cells were isolated from C57BL/6J mice with or without formalin-fixed P. gingivalis immunization. B cells were cultured for 48 hours under the following conditions: CD40L, CD40L+LPS, CD40L+CpG, and CD40L+LPS+CpG in the presence or absence of fixed P. gingivalis. Percentages of CD1dhiCD5+ B cells were measured by flow cytometry. IL-10 mRNA expression and secreted IL-10 were measured by real-time quantitative PCR and by ELISA respectively. Results P. gingivalis LPS plus CD40L significantly increased CD1dhiCD5+ B cell percentages and secreted IL-10 levels in both immunized and non-immunized mice B cells in the presence or absence of P. gingivalis, compared with control group. Secreted IL-10 levels were significantly increased in CD40L+LPS treated group compared with CD40L treatment group in the absence of P. gingivalis. CpG plus CD40L significantly decreased CD1dhiCD5+ B cell percentages, but greatly elevated secreted IL-10 levels in immunized and non-immunized mice B cells in the absence of P. gingivalis, compared with CD40L treatment group. Conclusions P. gingivalis LPS and CpG differentially enhance IL-10 secretion and expansion of mouse B10 cells during innate and adaptive immune responses.

Antioxidant activity of extract from Polygonum cuspidatum.

Numerous diseases are induced by free radicals via lipid peroxidation, protein peroxidation and DNA damage. It has been known that a variety of plant extracts have antioxidant activities to scavenge free radicals. Whether Polygonum cuspidatum Sieb. et Zuce has antioxidant activity is unknown. In this study, dried roots of Polygonum cuspidatum were extracted by ethanol and the extract was lyophilized. Free radical scavenging assays, superoxide radical scavenging assays, lipid peroxidation assays and hydroxyl radical-induced DNA strand scission assays were employed to study antioxidant activities. The results indicate that the IC50 value oí Polygonum cuspidatum extract is 110 microg/ml in free radical scavenging assays, 3.2 microg/ml in superoxide radical scavenging assays, and 8 microg/ml in lipid peroxidation assays, respectively. Furthermore, Polygonum cuspidatum extract has DNA protective effect in hydroxyl radical-induced DNA strand scission assays. The total phenolics and flavonoid content of extract is 641.1 +/- 42.6 mg/g and 62.3 +/- 6.0 mg/g. The results indicate that Polygonum cuspidatum extract clearly has antioxidant effects.

Antioxidant activity of extract from Polygonum cuspidatum

Numerous diseases are induced by free radicals via lipid peroxidation, protein peroxidation and DNA damage. It has been known that a variety of plant extracts have antioxidant activities to scavenge free radicals. Whether Polygonum cuspidatum Sieb. et Zuce has antioxidant activity is unknown. In this study, dried roots of Polygonum cuspidatum were extracted by ethanol and the extract was lyophilized. Free radical scavenging assays, superoxide radical scavenging assays, lipid peroxidation assays and hydroxyl radical-induced DNA strand scission assays were employed to study antioxidant activities. The results indicate that the IC50 value oí Polygonum cuspidatum extract is 110 µg/ml in free radical scavenging assays, 3.2 µg/ml in superoxide radical scavenging assays, and 8 µg/ml in lipid peroxidation assays, respectively. Furthermore, Polygonum cuspidatum extract has DNA protective effect in hydroxyl radical-induced DNA strand scission assays. The total phenolics and flavonoid content of extract is 641.1 ± 42.6 mg/g and 62.3 ± 6.0 mg/g. The results indicate that Polygonum cuspidatum extract clearly has antioxidant effects.