ABSTRACT
Background An association between atmospheric fine particulate matter (PM2.5) exposure and Parkinson's disease (PD) has been suggested by previous studies, but the results of current epidemiological studies are still inconclusive. Objective To systematically evaluate the relationship between exposure to ambient PM2.5 and the risk of PD, as well as to explore potential influencing factors, aiming to provide scientific evidence for formulating early prevention strategies for PD. Methods Cochrane Library, PubMed, Web of Science, Medline, Embase, China National Know-ledge Infrastructure (CNKI), Wanfang Database, and VIP Chinese Science and Technology Journal Database were queried. The search terms included Parkinson's disease, particulate matter 2.5, and PM2.5 in both Chinese and English. Cohort studies examining the association between atmospheric PM2.5 exposure and the risk of PD were collected and searched from the inception of each database to June 26, 2023. The identified literature was screened, and the basic information of the included studies and their research subjects, outcome indicators, quantitative results of each study, as well as the information required by bias risk assessment were extracted. The Newcastle-Ottawa Scale was employed to assess the risk of literature bias. Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias analysis were conducted in Stata 15.0 software. Results Twelve cohort studies were identified. A total of 17443136 participants with follow-up periods ranging from 3.5 to 22 years were included in the analysis. The meta-analysis, utilizing a random-effects model, revealed that PD risk was elevated by 6% after exposure to PM2.5 [HR=1.06 (95%CI: 1.02, 1.11), P=0.006]. The subgroup analysis demonstrated that exposure to PM2.5 increased PD risk by 6% in North America [HR=1.06 (95%CI: 1.00, 1.12), P=0.033] and by 17% in East Asia [HR=1.17 (95%CI: 1.02, 1.33), P=0.020]. However, the effect was not statistically significant in Europe. PD risk exhibited a 7% rise [HR=1.07 (95%CI: 1.02, 1.14), P=0.011] in individuals aged 60 years and older, which was different from that in individuals younger than 60 years. Exposure to various concentrations of PM2.5 was observed to associate with an elevated risk of PD. The inclusion of adjustments for PD-related comorbidities did not alter the conclusion that ambient PM2.5 exposure might elevate the risk of PD. The studies with a follow-up duration exceeding 5 years and reporting more than 1000 PD cases suggested a significant increase in the risk of PD due to ambient PM2.5 exposure [HR=1.06 (95%CI: 1.01, 1.12), P=0.012; HR=1.06 (95%CI: 1.01, 1.11), P=0.027, respectively]. Conversely, no significant association was identified between ambient PM2.5 exposure and the risk of PD within the cohorts with a follow-up duration of less than 5 years and reporting fewer than 1000 PD cases [HR=1.09 (95%CI: 0.95, 1.26), P=0.214; HR=1.12 (95%CI: 0.98, 1.02), P=0.092, respectively]. The sensitivity analysis showed that the results were stable. The publication bias analysis and the combined trim-and-fill method showed that the results were robust. Conclusion The risk of PD could be increased by ambient PM2.5 exposure and influenced by age and area. The research results might be affected by the duration of follow-up and the quantity of PD cases reported.
ABSTRACT
Objective:To investigate the effects and mechanisms of copper transporter 1 (CTR1) in radiation induced intestinal injury in vitro. Methods:Human small intestinal epithelial cells (HIEC) were irradiated with 2, 4, 6, 8 Gy of X-rays and rat intestinal epithelial cells (IEC-6) were irradiated with 5, 10, 15, 20 Gy of X-rays. At 2, 4, 8, 24, and 48 h after irradiation, the expression of CTR1 was detected by Western blot assay. In some experiments, HIEC and IEC-6 cells were transfected with CTR1 shRNA and then exposed to X-rays. Copper levels were detected by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The radiosensitivity of cells was verified by colonogenic assay, the cellular reactive oxygen species (ROS) level and DNA damage were detected to further explore the related mechanism. In addition, Western blot was applied to detect the expressions of antioxidants and cuproptosis associated proteins in enterocytes after silencing CTR1 or irradiation.Results:The expression of CTR1 was increased by X-ray irradiation in a dose-dependent manner ( t=3.53, 3.45, 6.37, 11.11, 11.13, P<0.05). CTR1 expression was successfully diminished by CTR1 shRNA adenovirus vectors. According to the survival curves, the enhancement ratios of the radiosensitivity of HIEC and IEC-6 cells with CTR1 knocking-down were 1.146 and 1.201, respectively. Radiation-induced copper accumulation was alleviated after CTR1 silencing in IEC-6 cells ( t=3.10, P<0.05). At 0.5 h after irradiation, the ROS production in the CTR1 knockdown group was significantly lower than that in the control group ( t=5.23, 2.96, P<0.05). At 1 h after irradiation, the protein expression of γ-H2AX in the CTR1 knockdown group was obviously lower than that in the control group ( t=7.50, 4.29, P<0.05). The expressions of Nrf2 and HO-1 were increased after irradiation, which could be further increased after CTR1 silencing. In addition, cuproptosis associated protein DLAT, LIAS and FDX1 were reduced post-irradiation, which were recovered after CTR1 silencing. Conclusions:The radioresistance of HIEC and IEC-6 cells was enhanced after CTR1 silencing, possibly through the intracellular ROS and cuproptosis pathway.
ABSTRACT
Object To study the antitumor effects of extracts from the fruits, roots and rhizomes of Sinopodophyllum emodi (Wall.) Ying, the roots and rhizomes of Dysosma furfuracea S.Y. Bao and the podophyllotoxin, deoxypodophyllotoxin of Guijiu plants in mice. Methods Tumor borne mice with transplanted HepA and Ehrlich ascites carcinoma (EAC) were used to observe the antitumor and the liver protective effects of the above five samples, which were given orally. Results Extracts of roots and rhizomes of S. emodi, and D. furfuracea showed the significant antitumor effects. Conclusion All the five samples have antitumor activity.