Optimal therapeutic conditions for the neural stem cell-based management of ischemic stroke: a systematic review and network meta-analysis based on animal studies.

BACKGROUND: In order to promote the clinical translation of preclinical findings, it is imperative to identify the most optimal therapeutic conditions and adopt them for further animal and human studies. This study aimed to fully explore the optimal conditions for neural stem cell (NSC)-based ischemic stroke treatment based on animal studies. METHODS: The PubMed, Ovid-Embase, and Web of Science databases were searched in December 2021. The screening of search results, extraction of relevant data, and evaluation of study quality were performed independently by two reviewers. RESULTS: In total, 52 studies were included for data analysis. Traditional meta-analysis showed that NSCs significantly reduced the modified neurological severity score (mNSS) and volume of cerebral infarct in animal models of ischemic stroke. Network meta-analysis showed that allogeneic embryonic tissue was the best source of NSCs. Further, intracerebral transplantation was the most optimal route of NSC transplantation, and the acute phase was the most suitable stage for intervention. The optimal number of NSCs for transplantation was 1-5×105 in mouse models and 1×106 or 1.8×106 in rat models. CONCLUSIONS: We systematically explored the therapeutic strategy of NSCs in ischemic stroke, but additional research is required to develop optimal therapeutic strategies based on NSCs. Moreover, it is necessary to further improve and standardize the design, implementation, measuring standards, and reporting of animal-based studies to promote the development of better animal experiments and clinical research.

PM2.5 and Serum Metabolome and Insulin Resistance, Potential Mediation by the Gut Microbiome: A Population-Based Panel Study of Older Adults in China.

BACKGROUND: Insulin resistance (IR) affects the development of type 2 diabetes mellitus (T2DM), which is also influenced by accumulated fine particle air pollution [particulate matter (PM) with aerodynamic diameter of <2.5µm (PM2.5)] exposure. Previous experimental and epidemiological studies have proposed several potential mechanisms by which PM2.5 contributes to IR/T2DM, including inflammation imbalance, oxidative stress, and endothelial dysfunction. Recent evidence suggests that the imbalance of the gut microbiota affects the metabolic process and may precede IR. However, the underlying mechanisms of PM2.5, gut microbiota, and metabolic diseases are unclear. OBJECTIVES: We investigated the associations between personal exposure to PM2.5 and fasting blood glucose and insulin levels, the IR index, and other related biomarkers. We also explored the potential underlying mechanisms (systemic inflammation and sphingolipid metabolism) between PM2.5 and insulin resistance and the mediating effects between PM2.5 and sphingolipid metabolism. METHODS: We recruited 76 healthy seniors to participate in a repeated-measures panel study and conducted clinical examinations every month from September 2018 to January 2019. Linear mixed-effects (LME) models were used to analyze the associations between PM2.5 and health data (e.g., functional factors, the IR index, inflammation and other IR-related biomarkers, metabolites, and gut microbiota). We also performed mediation analyses to evaluate the effects of mediators (gut microbiota) on the associations between exposures (PM2.5) and featured metabolism outcomes. RESULTS: Our prospective panel study illustrated that exposure to PM2.5 was associated with an increased risk of higher IR index and functional biomarkers, and our study provided mechanistic evidence suggesting that PM2.5 exposure may contribute to systemic inflammation and altered sphingolipid metabolism. DISCUSSION: Our findings demonstrated that PM2.5 was associated with the genera of the gut microbiota, which partially mediated the association between PM2.5 and sphingolipid metabolism. These findings may extend our current understanding of the pathways of PM2.5 and IR. https://doi.org/10.1289/EHP9688.

Associations between Personal PM2.5 Elemental Constituents and Decline of Kidney Function in Older Individuals: the China BAPE Study.

Long-term exposure to fine particulate matter (PM2.5) is associated with kidney dysfunction. However, few studies have investigated acute effects of PM2.5 elemental constituents on renal function. We evaluated associations between personal PM2.5 and its elemental constituents and kidney function, assessed by an estimated glomerular filtration rate (eGFR) in Biomarkers of Air Pollutants Exposure in the Chinese aged 60-69 study. Seventy one older individuals were visited monthly between September 2018 and January 2019. Each participant wore a PM2.5 monitor for 72 h, responded to a questionnaire, and underwent a physical examination with blood sampling. Linear mixed-effect models were used to estimate associations between personal PM2.5 elemental constituents and eGFR. We found that significant changes in eGFR from -1.69% [95% confidence interval (CI): -3.34%, -0.01%] to -3.27% (95% CI: -5.04%, -1.47%) were associated with interquartile range (IQR) increases in individual PM2.5 exposures at various lag periods (7-12, 13-24, 0-24, 25-48, and 49-72 h). An IQR increase in 72 h moving averages of copper, manganese, and titanium in personal PM2.5 corresponded to -2.34% (95% CI: -3.67%, -0.99%) to -4.56% (95% CI: -7.04%, -2.00%) changes in eGFR. Personal PM2.5 and some of its elemental constituents are inversely associated with eGFR in older individuals.

Personal black carbon exposure and its determinants among elderly adults in urban China.

Personal exposure to air pollution is affected by its concentration in the microenvironment and individual time-activity patterns. To investigate personal black carbon (BC) exposure levels and identify their potential determinants, we conducted a panel study among 67 elderly residents aged 60-69 years in Jinan, China. Personal BC exposure was measured using portable real-time monitors, while corresponding ambient BC concentrations and meteorological conditions were also collected from the local central site. Time-activity and household characteristics were recorded. A linear mixed-effects model was used to identify potential determinants of personal BC exposure. The daily average personal BC exposure concentration was 4.1 ± 2.0 µg/m3 (±standard deviation, SD), which was significantly lower than the ambient concentration (4.6 ± 2.5 µg/m3) (p < 0.001). Strong correlation (Spearman's r = 0.63, p < 0.001) was found between personal and ambient BC concentrations. The fixed-site monitoring ambient concentration cannot fully reflect the actual personal exposure concentration. Ambient BC concentration, ambient temperature, relative humidity, education level and air purifier use were significant determinants of personal BC exposure. Our findings highlight the need for detailed assessment of personal exposure on health risk assessment of BC and also help develop strategies for targeted risk reduction.

Particulate matter air pollution and the expression of microRNAs and pro-inflammatory genes: Association and mediation among children in Jinan, China.

Exposure to particulate matter (PM) has been associated with increased risk of various diseases, possibly through its effect on inflammatory response. MicroRNAs (miRNAs), an epigenetic mechanism regulating gene expression, can affect the expression of pro-inflammatory genes. However, few epidemiological studies have examined the impact of PM on inflammation-related miRNAs and their target mRNAs, especially among vulnerable population. We recruited 160 and 113 children from areas with different PM level in Jinan, China. We measured benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts in serum and the expression of 5 candidate miRNAs involved in inflammation regulation and 7 pro-inflammatory genes predicted to be their targets in leukocytes. Generally, children in the polluted area had higher miRNAs and lower mRNAs expression than those in the control area. An interquartile increase of BPDE-Alb adducts was associated with 12.66 %, 14.13 %, and 12.76 % higher of let-7a, miR-146a-5p, and miR-155-5p, as well as 21.61 %, 20.16 %, and 12.49 % lower of IL-6, CXCL8, and TLR2 mRNAs at false discovery rate<0.05, respectively. Additionally, let-7a, miR-146a-5p, and miR-155-5p were found to mediate the associations of BPDE-Alb adducts with IL-6 and/or TLR2 expression. Our findings suggested that PM exposure might attenuate inflammatory response among children in China, which was partly mediated by miRNAs regulating pro-inflammatory genes.

Air pollution exposure and immunological and systemic inflammatory alterations among schoolchildren in China.

Exposure to air pollution is associated with an increased risk of respiratory infection, to which children are more susceptible than adults. However, epidemiological evidence regarding the association of chronic exposure to air pollution with the immune and systemic inflammatory function of children is scarce, especially in the context of higher exposure levels. In this study, we included 163 chronically exposed schoolchildren from a polluted area and 110 schoolchildren from a control area in Licheng district, Jinan, China. Immune biomarkers, including the absolute counts of lymphocyte subsets and the levels of immunoglobulins G, A, and M, C3, and C4 were determined. To explore the related biological process of altered immune biomarkers, 2 systemic inflammatory biomarkers, including C-reactive protein and the neutrophil-to-lymphocyte ratio, were also determined. After adjusting for confounders, the decreased B lymphocyte count (p = 0.021) and C3 and C4 levels (both p < 0.001) and the increased monocyte count (p = 0.009) and CD8+ T lymphocyte proportion (p = 0.054) were associated with living in the polluted area. Significant differences in the C4 and C3 levels between the areas were only seen in male schoolchildren and in schoolchildren without passive smoking exposure (Pinteraction = 0.036 and 0.042, respectively). The alterations in immune biomarkers suggested that air pollution-induced immunotoxic effects and relevant adaptive responses were simultaneously present in schoolchildren exposed to a higher level of air pollution. Future studies investigating the temporal patterns of these biomarkers among children are warranted.

Disruption of thyroid hormone levels by decabrominated diphenyl ethers (BDE-209) in occupational workers from a deca-BDE manufacturing plant.

While there is some evidence that exposure to decabrominated diphenyl ethers (BDE-209) affects thyroid function, the results obtained to date have been inconsistent. No studies have been performed on workers in deca-BDE manufacturing who had a high level of exposure to BDE-209 and relatively little exposure to other contaminants. In the present study, the relationship between BDE-209 exposure and thyroid hormone in occupational workers from a deca-BDE manufacturing plant was investigated. The serum and urine levels of polybrominated diphenyl ethers (PBDEs) and serum thyroid hormones were measured in 72 workers recruited from the deca-BDE manufacturing plant. The associations between their thyroid hormone levels and their exposure to BDE-209 were examined using multiple linear regression models. Serum concentrations of BDE-209 ranged from 67.4 to 109,000 ng/g lipid weight (lw), with a median of 3420 ng/g lw, contributing to 93.1% of the total PBDEs. The concentration of BDE-209 in urine was highly correlated with that in the serum (r2 = 0.440, p < 0.001), indicating that urine may be a good non-invasive biomonitoring medium of BDE-209 body burden in occupational workers. BDE-209 in the serum was significantly and positively correlated with total thyroxine (tT4, r = 0.270, p = 0.029) and marginally and positively correlated with total triiodothyronine (tT3, r = 0.232, p = 0.061) in all occupational workers after adjusting for gender, age, BMI, and occupational exposure duration. A 10-fold increase in the serum BDE-209 concentration was associated with an increase in tT4 (8.63 nmol/L) [95% confidence interval (CI): 0.930-16.3] and tT3 (0.106 nmol/L) [95% confidence interval (CI): -0.005-0.219], corresponding to the increase of 7.8% in tT4 level and 5.4% in tT3 level. Associations between urine BDE-209 levels and thyroid hormones were similar to the results for the serum levels. These findings offer new evidence for proving the thyroid disrupting effects of BDE-209, impacting the direction of hyperthyroidism.

Cardiopulmonary effects induced by occupational exposure to titanium dioxide nanoparticles.

Although some toxicological studies have reported that exposure to titanium dioxide nanoparticles (nano-TiO2) may elicit adverse cardiopulmonary effects, related data collected from human are currently limited. The purpose of this study is to explore cardiopulmonary effects among workers who were exposed to nano-TiO2 and to identify biomarkers associated with exposure. A cross-sectional study was conducted in a nano-TiO2 manufacturing plant in eastern China. Exposure assessment and characterization of TiO2 particles were performed in a packaging workshop. Physical examination and possible biomarkers for cardiopulmonary effects were examined among 83 exposed workers and 85 controls. In packaging workshop, the total mass concentration of particles was 3.17 mg/m3. The mass concentration of nanoparticles was 1.22 mg/m3 accounting for 39% of the total mass. Lung damage markers (SP-D and pulmonary function), cardiovascular disease markers (VCAM-1, ICAM-1, LDL, and TC), oxidative stress markers (SOD and MDA), and inflammation markers (IL-8, IL-6, IL-1ß, TNF-α, and IL-10) were associated with occupational exposure to nano-TiO2. Among those markers, SP-D showed a time (dose)-response pattern within exposed workers. The data strongly suggest that nano-TiO2 could contribute, at least in part, to the cardiopulmonary effects observed in workers. The studied markers and pulmonary function tests may be useful in health surveillance for workers exposed to nanomaterials.

[Risk assessment and risk control for occupational exposure to chemical toxicants from an isophorone nitrile device].

OBJECTIVE: Risk assessment and risk control for occupational exposure to chemical toxicants were performed on an isophorone nitrile device with an annual production of 5,000 tons, based on improved Singaporean semi-quantitative risk assessment method, with consideration of actual situation in China and in the present project. METHODS: With the use of engineering analysis and identification of occupational hazards in the improved Singaporean semi-quantitative risk assessment method, hazard rating (HR) and risk assessment were performed on chemical toxicants from an isophorone nitrile device with an annual production of 5,000 tons. RESULTS: The chemical toxicants in the isophorone nitrile device were mainly isophorone, hydrocyanic acid, methanol, phosphoric acid, sodium hydroxide, and sodium cyanide; the HR values were mild hazard (2), extreme hazard (5), mild hazard (2), mild hazard (2), moderate hazard (3), and extreme hazard (5), respectively, and the corresponding exposure rating (ER) values were 2.09, 2.72, 2.76, 1.68, 2.0, and 1.59, respectively. The risk of chemical toxicants in this project was assessed according to the formula Risk = [HR×ER](1/2). Hydrocyanic acid was determined as high risk, sodium hydroxide and sodium cyanide as medium risk, and isophorone, methanol, and phosphoric acid as low risk. Priority in handling of risks was determined by risk rating. The table of risk control measure was established for pre-assessment of occupational hazards. CONCLUSION: With risk assessment in this study, we concluded that the isophorone nitrile device with 5,000 ton annual production was a high-occupational hazard device. This device is a project of extreme occupational hazard. The improved Singaporean semi-quantitative risk assessment method is a scientific and applicable method, and is especially suitable for pre-evaluation of on-site project with no analogy.

The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene.

1,3-Butadiene (BD) has been classified as a human carcinogen, group I; however, the relationship between polymorphisms of glutathione S-transferases that metabolize BD and chromosomal damage is not clear. The present study used sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays to detect chromosomal damage in peripheral lymphocytes of 44 BD-exposed workers and 39 non-exposed healthy controls. PCR and PCR-RFLP were employed to detect three known glutathione S-transferase polymorphisms GSTT1, GSTM1, and GSTP1 (Ile105Val). The data demonstrated that the micronucleus (CBMN) frequency in BD-exposed workers was significantly higher than that in controls (frequency ratio (FR)=1.48, 95% CI: 1.14-1.91, P<0.01), and the CBMN frequency was higher in workers exposed to higher cumulative BD levels (FR=1.70, 95% CI: 1.28-2.27, P<0.01). However, differences in SCE frequency were not observed (FR=1.14, 95% CI: 0.81-1.61, P>0.05). Among exposed workers, chromosomal damage was related to BD exposure levels (FR=1.35, 95% CI: 1.02-1.80, P<0.05); age, older workers exhibited higher MN frequencies than younger workers (FR=1.45, 95% CI: 1.14-1.84, P<0.05); and years of work, those with more years of work exhibited higher MN frequencies than those with fewer years (FR=1.40, 95% CI: 1.10-1.77, P<0.05). Multivariate Poisson regression analysis showed that those who carried GSTM1 (-) (FR=1.48, 95% CI: 1.14-1.92) or GSTT1 (-) (FR=1.42, 95% CI: 1.10-1.83) genotypes, and especially those who carried both (FR=2.10, 95% CI: 1.43-3.09) exhibited significantly higher MN frequencies than those carrying GSTM1 (+), GSTT1 (+) genotypes or their combination. The GSTP1 Val genotype did not affect MN frequency (P>0.05). Our results suggested that higher levels of BD exposure in the workplace resulted in increased chromosomal damage, and that polymorphisms in GSTT1 and GSTM1 genes might modulate the genotoxic effects of BD exposure. Furthermore, the GSTT1 and GSTM1 polymorphisms exhibited an additive effect. Finally, urinary DHBMA was found to provide a biomarker that correlated with airborne BD levels.

[Analysis on occupational exposure levels and control effectiveness of dust in cement production line of new dry method].

OBJECTIVE: To investigate the occupational exposure levels of dust in new suspension preheated dry process (NSP) cement production line and put forward rectification measures for dust-exposed posts, and to provide ideas for the modern cement production enterprises in dust control and occupational health management. METHODS: Occupational health field investigation combined with field test were used to measure the time-weighted average concentration (C(TWA)) of the dust in the workplace. Rectification measures were taken for the dust-exposed posts with unqualified dust concentration, and the protective effects of dustproof facilities in the rectified workplace were evaluated. RESULTS: The field investigation revealed incompletely closed dustproof facilities, improperly set dust hoods, excess of dust leakage points, and other problems in the dust-exposed posts of an NSP cement production line before rectification, and the dustproof facilities could hardly exert dust removal effect. The field test showed that the vast majority of dust-exposed posts had the dust concentrations exceeding the occupational exposure limits (OELs), with a qualified rate as low as 31.8%. A series of rectification measures were taken for these posts. After the rectification, the dust-exposed posts demonstrated dramatically dropped C(TWA), and the qualified rate of dust concentration in the dust-exposed posts rose to 90.9%. CONCLUSION: The dust hazards in NSP cement production line cannot be ignored. Taking appropriate protective measures are critical for curbing dust hazards in modern cement production.

[Study on association of interleukin-1 receptor antagonist(RA) gene + 2018 locus mutation with silicosis].

OBJECTIVE: To approach whether + 2018 locus (T-- C) mutation within the interleukin- receptor antagonist (IL-1RA) gene promoter region are associated with susceptibility to silicosis in Southwest Chinese Han population. METHODS: 75 cases of silicosis and 137 silica-exposed workers(being employed) were selected as subjects.5ml peripheral vein blood was drawn from each subject. By real-time quantitative polymerase chain reaction and sequencing techniques, IL-1RA gene mutation of all subjects were analyzed. RESULTS: The frequency of IL-1RA + 2018C among the cases with silicosis was higher than that among the silica-exposed workers (controls) (28.0% versus 15.0% , Fisher' s exact P < 0.01 ). The frequency of allelic C was higher in cases with phase I silicosis than in controls(31.8% versus 15.0%, Fisher's exact P < 0.01 ). The frequency of allelic C was higher in cases with phase I and Ill silicosis than in controls, but which statistic difference being not significant(22.6% versus 15.0%, Fisher's exact P < 0.01). After adjusted for confounding factors, the frequency of IL-1RA + 2018C among silicoses and its subgroups was still higher than among controls, which statistic difference being significant (Fisher' s exact P < 0.01). CONCLUSION: IL-1RA gene polymorphisms played an important role in making the Han population of Southwest China susceptible to silicosis. IL-1RA might be took as a gene to be selected for studying the susceptibility of silicosis.

[An analysis about genetic basis of cotton cultivars in China since 1949 with molecular markers].

The diversity of 166 cotton cultivars(cult.) including 159 upland(G. hirsutum L) and 7 island(G. barbadense L) ones planted mainly in China since 1949 was explored by RAPD, genetic distance(GD) and cluster analysis. The correlation coefficients between Nei's GD of RAPDs and two groups of phenotype data's Euclidean distances (UD) were 0.6445(n = 1770) and 0.7078 (n = 7140), which indicated that RAPD could be used to explore genetic diversity among cotton cultivars in China. The genetic basis of cotton cultivars in China was studied by comparison among different cotton species, different cultivar types, different history periods, different growing regions and different sources. The results showed as follows:within cotton cultivars planted in China, the genetic basis of island cotton cultivars was narrower than that in upland ones; the genetic basis of cultivars released in China since 1949 was narrower than that of introduced ones from outside of China; the genetic basis of hybrids was narrower than that of conventional cultivars(Conv. Cult.); the genetic basis of upland cultivars after 1980 was narrower than that in 1970's; the genetic basis of cultivars in Changjiang cotton region was narrower than that of Huanghuai cotton region, northwestward cotton region was the narrowest. From which some strategies for breeding, especially for the methods of widening the genetic basis of China cotton cultivars, could be understood and withdrawn.