Pretreatment with brain-derived neurotrophic factor (BDNF) reduces ischemic damage after focal cerebral ischemia, and bone marrow mesenchymal stem cells(MSCs) were reported to ameliorate functional deficits after stroke in rats. Here we investigate the synergistically therapeutic effects of BDNF gene-modified MSCs on cerebral infarction. We transfected MSCs with the BDNF gene using a lentivirus-based system and investigated whether the BDNF-modified MSCs contributed to improved functional recovery in a rat transient middle cerebral artery occlusion (MCAO) model. Compared to untreated rats, rats that received both MSCs and BDNF-MSCs showed significantly more functional recovery. The difference in modified neurological severity score(mNSS) was statistically significant (P < 0.001). Recovery was better in BDNF-MSCs than in MSCs (P < 0.001). At the second week and second month after the systemic delivery of blank vector-modified MSCs and BDNF-modified MSCs, the treated rats exhibited more significant recovery than the control, including the accumulation and living of enhanced green fluorescence protein (EGFP)-positive cells in the infarct area and surrounding areas, neuron-like changes, expression of surface markers of neural cells, and a large amount of BDNF expression in the BDNF-MSCs-treated group. Our findings suggest that BDNF-gene-modified rMSCs can migrate to surrounding areas of the cerebral infarction lesion, differentiate into neural cells, and survive for extended periods. With the synergy of BDNF, they may promote the recovery of the neurological function following cerebral infarction and represent a new strategy for stem cell-based therapy.
Animals ; Brain-Derived Neurotrophic Factor ; biosynthesis ; genetics ; Genetic Vectors ; genetics ; Infarction, Middle Cerebral Artery ; genetics ; therapy ; Lentivirus ; genetics ; metabolism ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Rats ; Rats, Inbred F344 ; Recovery of Function ; Transfection

Generation of bio-engineered teeth by using stem cells will be a major approach for bioengineered implantation. Previous studies have demonstrated that dissociated tooth germ cells are capable of generating a tooth after reaggregation in vitro. However, the cellular and molecular mechanisms underlying this tooth regeneration are not clear. In this study, we dispersed E13.5 molar germ into single cells, immediately reaggregated them into cell pellet, then grafted the reaggregates under mouse kidney capsule for various times of culture. We investigated the morphogenesis and the expression of several developmental genes in dental epithelial cells in reaggregates of tooth germ cells. We found that dissociated tooth germ cells, after reaggregation, recapitulated normal tooth developmental process. In addition, dissociated dental epithelial cells retained the expression of Fgf8, Noggin, and Shh during reaggregation and tooth regeneration processes. Our results demonstrated that, despite of under dissociated status, dental epithelial cells maintained their odontogenic fate after re-aggregation with dental mesenchymal cells. These results provided important information for future in vitro generation of bio-engineered teeth from stem cells.
Animals ; Cell Culture Techniques ; methods ; Cell Differentiation ; Embryo, Mammalian ; Epithelial Cells ; cytology ; metabolism ; Female ; Gene Expression Regulation, Developmental ; genetics ; Male ; Mice ; Odontogenesis ; genetics ; Tooth Germ ; cytology ; physiology

Background Exposure to air pollutants O₃ and PM_2.5 is closely related to population mortality. Most of the domestic research findings are for residents in coastal areas, and less for those in the central and western regions. Objective To investigate the acute effects of O₃ and PM_2.5 on the mortality of residents in a city of central China. Methods Data were collected on atmospheric pollutants, meteorological data, and population mortality in a city of central China from January 1, 2015 to June 30, 2021. Meteorological data included daily average temperature, air pressure, and relative humidity. Atmospheric pollution data included daily mean concentrations of PM_2.5, PM₁₀, SO₂, NO₂, and CO and maximum 8 h O₃. Generalized additive model with Poisson distribution was used for estimating the relationships between air pollutants (O₃ and PM_2.5) and population mortality, and further stratified by age, gender, and education. Results The daily maximum 8 h average concentration of O₃ in the city during the study period was 94.38 μɡ·m⁻³ and the daily average concentration of PM_2.5 was 55.56 μɡ·m⁻³. In the single-pollutant model, the correlations between O₃ concentration and total deaths as well as deaths due to respiratory, circulatory, hypertension, coronary heart disease, and stroke were strongest at lag02, lag2, lag02, lag0, lag02, and lag0, and for every 10 μɡ·m⁻³ increase in concentration of O₃, the associated ER (95%CI) values of daily mortality were increased by 0.09% (−0.08%–0.25%), 0.35% (0–0.71%), 0.43% (0.18%–0.68%), 0.45% (0.02%–0.91%), 0.59% (0.16%–1.02%), and 0.33% (0.01%–0.65%), respectively. The effect of O₃ on total mortality was not statistically significant (P>0.05). The correlations between PM_2.5 concentration and total deaths, as well as deaths due to respiratory, circulatory, hypertension, coronary heart disease, and stroke were strongest at lag1, lag5, lag01, lag05, lag04, and lag01, and for every 10 μɡ·m⁻³ increase in concentration of PM_2.5, the associated ER (95%CI) values of daily mortality increased by 0.02% (−0.09–0.13%), 0.25% (0.01%–0.50%), 0.35% (0.16%–0.54%), 1.18% (0.59%–1.77%), 0.17% (−0.13%–0.40%), and 0.65% (0.38%–0.92%), respectively, with no statistically significant effects of PM_2.5 on total mortality and mortality due to coronary heart disease (P>0.05). During warm season (from May to October), the ER (95%CI) values of total deaths per 10 μɡ·m⁻³ increase in O₃ in male, people aged 6~65 years, people aged >65 years, and people below high school education were 0.46% (0.16%–0.75%), 0.38% (0.08%–0.68%), 0.41% (0.14%–0.66%), and 0.38% (0.14%–0.61%), respectively, while the O₃ effect was not statistically significant (P>0.05) during cool season (from November to April). Conclusions Atmospheric pollutants (O₃ and PM_2.5) have acute effects on mortality in the city, with the elderly, people with less than a high school education, and those with circulatory disease being more sensitive to O₃ and PM_2.5 exposures.

Background In recent years, our country's atmospheric particulate matter pollution has improved significantly, while ozone (O₃) pollution has become increasingly serious. As a secondary pollutant, O₃ is closely related to human health. Objective To study the effect of short-term exposure to ozone in ambient air on population mortality in China. Methods A computer search with key words of "ozone or O₃", "death", and "time series" in Chinese or "ozone", "mortality", and "China" in English was performed in Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, and VIP databases to find literature on effects of short-term ozone exposure on population mortality covering a time period from January 1, 1990 to December 31, 2021. According to a set of inclusion and exclusion criteria developed for this study, literaturescreening, quality evaluation, andrelevant data extraction were carried out. Finally, R 4.1.2 software was used to perform meta-analysis to estimate target effect sizes. Results A total of 978 articles were retrieved. According to the inclusion and exclusion criteria, 18 articles were finally included, including 39 effect size estimates. The results showed that every 10 μɡ·m⁻³ increase in ambient ozone concentration was associated with an increase of 0.45% (95%CI: 0.39%-0.51%), 0.50% (95%CI: 0.33%-0.68%), and 0.60% (95%CI: 0.48%-0.72%) in total, respiratory, and cardiovascular disease mortalities , respectively. The results of subgroup analysis by age, sex, and season showed that when ozone concentration increased 10 μɡ·m⁻³, an increase of 0.34% (95%CI: 0.17%-0.51%) in mortality was observed in the ≥ 65-year-old population, higher than 0.09% (95%CI: −0.21%-0.39%) increase in the <65-year-old population; the mortality increase in females [0.44% (95%CI: 0.30%-0.58%)] was greater than that in males [0.35% (95%CI: 0.22%-0.48%)]; compared with the warm season [0.29% (95%CI: 0.16%-0.42%)], mortality increase was higher in the cold season [1.03% (95%CI: 0.71%-1.35%)]. Conclusion Ambient ozone is an important factor affecting population mortality. The elderly and women ≥ 65 years old in China are more sensitive to ozone, and the impact of ozone exposure on population mortality is greater in cold season.

Objective To explore the research progress, research hotspot and development trend of tigecycline resistance based on the quantitative analysis and visualization function of CiteSpace. Methods The data were collected from 4,263 Chinese and English articles on tigecycline resistance in CNKI, Wanfang, VIP and Web of Science (WOS) databases from 2012 to 2022. CiteSpace 5.8.R3 software was used to analyze the cooperative network of authors, the cooperative network of countries and institutions, the total citation times of journals, and keywords included in the literature, to reveal the hotspots and trends of tigecycline resistance research. Results The number of articles published in English literature was higher than that in Chinese literature. China had the largest number of published documents, showing a significant international academic influence in this research field. Countries all over the world were concerned about the resistance of tigecycline, but Chinese literatures focused more on the clinical infection and prevention of tigecycline resistance, while English literatures placed special emphasis on the research about the drug resistance mechanism of tigecycline. Conclusion The research direction at home and abroad is basically the same, but the research focus has gradually shifted from the clinical treatment and monitoring of tigecycline to the molecular level of drug resistance mechanism.