We performed this meta-analysis to estimate the associations of maternal exposure to PM2.5 and its chemical constituents with birth weight and to explore the sources of heterogeneity in regard to the findings of these associations. A total of 32 studies were identified by searching the MEDLINE, PUBMED, Embase, China Biological Medicine and Wanfang electronic databases before April 2015. We estimated the statistically significant associations of reduced birth weight (β = -15.9 g, 95% CI: -26.8, -5.0) and LBW (OR = 1.090, 95% CI: 1.032, 1.150) with PM2.5 exposure (per 10 μg/m(3) increment) during the entire pregnancy. Trimester-specific analyses showed negative associations between birth weight and PM2.5 exposure during the second (β = -12.6 g) and third (β = -10.0 g) trimesters. Other subgroup analyses indicated significantly different pooled-effect estimates of PM2.5 exposure on birth weight in studies with different exposure assessment methods, study designs and study settings. We further observed large differences in the pooled effect estimates of the PM2.5 chemical constituents for birth weight decrease and LBW. We concluded that PM2.5 exposure during pregnancy was associated with lower birth weight, and late pregnancy might be the critical window. Some specific PM2.5 constituents may have larger toxic effects on fetal weight. Exposure assessment methods, study designs and study settings might be important sources of the heterogeneity among the included studies.
In this study, gold nanorods (GNRs) were incorporated into the hydrogel networks formed by the copolymerization of N-isopropylacrylamide (NIPAm) and methacrylated poly-β-cyclodextrin (MPCD)-based macromer to fabricate an injectable and near-infrared (NIR)/pH-responsive poly(NIPAm-co-MPCD)/GNRs nanocomposite hydrogel, which could serve as a long-acting implant for chemophotothermal synergistic cancer therapy. The nanocomposite hydrogel showed superior mechanical and swelling properties, gelation characteristics, and excellent NIR-responsive property. A hydrophobic acid-labile adamantane-modified doxorubicin (AD-DOX) prodrug was loaded into the hydrogel efficiently by host-guest interaction. The nanocomposite hydrogel exhibited a manner of sustained drug release and could sustain the slow and steady release of DOX for more than 1 month. The pH-responsive release of DOX from the nanocomposite hydrogel was observed owing to the cleavage of acid-labile hydrazone bond between DOX and the adamantyl group in acidic environment. NIR irradiation could accelerate the release of DOX from the networks, which was controlled by the collapse of the hydrogel networks induced by photothermal effect of GNRs. The in vitro cytotoxicity test demonstrated the excellent biocompatibility and photothermal effect of the nanocomposite hydrogel. Moreover, the in situ-forming hydrogel showed promising tissue biocompatibility in the mouse model study. The in vivo antitumor test demonstrated the capacity of the nanocomposite hydrogel for chemophotothermal synergistic therapy with reduced adverse effects owing to the prolonged drug retention in the tumor region and efficient photothermal effect. Therefore, this injectable and NIR/pH-responsive nanocomposite hydrogel exhibited great potential as a long term drug delivery platform for chemophotothermal synergistic cancer therapy.
Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors. Oxa(IV)@ZnPc@M exhibits an anti-tumor M1 phenotype polarization and can efficiently home to primary and bone metastatic tumors. Additionally, therapeutics inside Oxa(IV)@ZnPc@M undergo NIR triggered release, which can kill primary tumors via combined chemo-photodynamic therapy and induce immunogenic cell death simultaneously. Oxa(IV)@ZnPc@M combined with anti-PD-L1 can eliminate primary and bone metastatic tumors, activate tumor-specific antitumor immune response, and improve overall survival with limited systemic toxicity. Therefore, this all-in-one macrophage provides a treatment platform for effective therapy of primary and bone metastatic tumors.
BackgroundAlthough several previous studies have assessed the association of fine particulate matter (PM2.5) exposure during pregnancy with preterm birth, the results have been inconsistent and remain controversial. This meta-analysis aims to quantitatively summarize the association between maternal PM2.5 exposure and preterm birth and to further explore the sources of heterogeneity in findings on this association.MethodsWe searched for all studies published before December 2014 on the association between PM2.5 exposure during pregnancy and preterm birth in the MEDLINE, PUBMED and Embase databases as well as the China Biological Medicine and Wanfang databases. A pooled OR for preterm birth in association with each 10 μg/m3 increase in PM2.5 exposure was calculated by a random-effects model (for studies with significant heterogeneity) or a fixed-effects model (for studies without significant heterogeneity).ResultsA total of 18 studies were included in this analysis. The pooled OR for PM2.5 exposure (per 10 μg/m3 increment) during the entire pregnancy on preterm birth was 1.13 (95 % CI = 1.03–1.24) in 13 studies with a significant heterogeneity (Q = 80.51, p < 0.001). The pooled ORs of PM2.5 exposure in the first, second and third trimester were 1.08 (95 % CI = 0.92–1.26), 1.09 (95 % CI = 0.82–1.44) and 1.08 (95 % CI = 0.99–1.17), respectively. The corresponding meta-estimates of PM2.5 effects in studies assessing PM2.5 exposure at individual, semi-individual and regional level were 1.11 (95 % CI = 0.89–1.37), 1.14 (95 % CI = 0.97–1.35) and 1.07 (95 % CI = 0.94–1.23). In addition, significant meta-estimates of PM2.5 exposures were found in retrospective studies (OR = 1.10, 95 % CI = 1.01–1.21), prospective studies (OR = 1.42, 95 % CI = 1.08–1.85), and studies conducted in the USA (OR = 1.16, 95 % CI = 1.05–1.29).ConclusionsMaternal PM2.5 exposure during pregnancy may increase the risk of preterm birth,but significant heterogeneity was found between studies. Exposure assessment methods, study designs and study settings might be important sources of heterogeneity, and should be taken into account in future meta-analyses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-015-0738-2) contains supplementary material, which is available to authorized users.
Cancer metastases is still a hurdle for good prognosis and live quality of breast cancer patients. Treatment strategies that can inhibit metastatic cancer while treating primary cancer are needed to improve the therapeutic effect of breast cancer.Methods: In this study, a dual functional drug conjugate comprised of protoporphyrin IX and NLG919, a potent indoleamine-2,3-dioxygenase (IDO) inhibitor, is designed to combine photodynamic therapy and immune checkpoint blockade to achieve both primary tumor and distant metastases inhibition. Liposomal delivery is applied to improve the biocompatibility and tumor accumulation of the drug conjugate (PpIX-NLG@Lipo). A series of in vitro and in vivo experiments were carried out to examine the PDT effect and IDO inhibition activity of PpIX-NLG@Lipo, and subsequently evaluate its anti-tumor capability in the bilateral 4T1 tumor-bearing mice.Results: The in vitro and in vivo experiments demonstrated that PpIX-NLG@Lipo possess strong ability of ROS generation to damage cancer cells directly through PDT. Meanwhile, PpIX-NLG@ Lipo can induce immunogenic cell death to elicit the host immune system. Furthermore, PpIX-NLG@Lipo interferes the activity of IDO, which can amplify PDT-induced immune responses, leading to an increasing amount of CD8+ T lymphocytes infiltrated into tumor site, finally achieve both primary and distant tumor inhibition.Conclusion: This work presents a novel conjugate approach to synergize photodynamic therapy and IDO blockade for enhanced cancer therapy through simultaneously inhibiting both primary and distant metastatic tumor.
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