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1.
Cell Stem Cell ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38908380

ABSTRACT

The intricate anatomical structure and high cellular density of the myocardium complicate the bioengineering of perfusable vascular networks within cardiac tissues. In vivo neonatal studies highlight the key role of resident cardiac macrophages in post-injury regeneration and angiogenesis. Here, we integrate human pluripotent stem-cell-derived primitive yolk-sac-like macrophages within vascularized heart-on-chip platforms. Macrophage incorporation profoundly impacted the functionality and perfusability of microvascularized cardiac tissues up to 2 weeks of culture. Macrophages mitigated tissue cytotoxicity and the release of cell-free mitochondrial DNA (mtDNA), while upregulating the secretion of pro-angiogenic, matrix remodeling, and cardioprotective cytokines. Bulk RNA sequencing (RNA-seq) revealed an upregulation of cardiac maturation and angiogenesis genes. Further, single-nuclei RNA sequencing (snRNA-seq) and secretome data suggest that macrophages may prime stromal cells for vascular development by inducing insulin like growth factor binding protein 7 (IGFBP7) and hepatocyte growth factor (HGF) expression. Our results underscore the vital role of primitive macrophages in the long-term vascularization of cardiac tissues, offering insights for therapy and advancing heart-on-a-chip technologies.

2.
Bioeng Transl Med ; 9(3): e10581, 2024 May.
Article in English | MEDLINE | ID: mdl-38818123

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been a major global health concern since its emergence in 2019, with over 680 million confirmed cases as of April 2023. While COVID-19 has been strongly associated with the development of cardiovascular complications, the specific mechanisms by which viral infection induces myocardial dysfunction remain largely controversial as studies have shown that the severe acute respiratory syndrome coronavirus-2 can lead to heart failure both directly, by causing damage to the heart cells, and indirectly, by triggering an inflammatory response throughout the body. In this review, we summarize the current understanding of potential mechanisms that drive heart failure based on in vitro studies. We also discuss the significance of three-dimensional heart-on-a-chip technology in the context of the current and future pandemics.

3.
Sci Adv ; 10(13): eadk0164, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38536913

ABSTRACT

Despite tremendous progress in the development of mature heart-on-a-chip models, human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip with circulating immune cells to model severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced acute myocarditis. We observed hallmarks of coronavirus disease (COVID-19)-induced myocardial inflammation, as the presence of immune cells augmented the secretion of proinflammatory cytokines, triggered progressive impairment of contractile function, and altered intracellular calcium transients. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the heart-on-a-chip and then validated in COVID-19 patients with low left ventricular ejection fraction, demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation-induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2-induced myocardial inflammation, we established that administration of endothelial cell-derived exosomes effectively rescued the contractile deficit, normalized calcium handling, elevated the contraction force, and reduced the ccf-mtDNA and cytokine release via Toll-like receptor-nuclear factor κB signaling axis.


Subject(s)
COVID-19 , Exosomes , Myocarditis , Humans , DNA, Mitochondrial/genetics , Stroke Volume , Calcium , Ventricular Function, Left , Inflammation , SARS-CoV-2 , Cytokines
4.
Proc Natl Acad Sci U S A ; 120(50): e2309472120, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38060560

ABSTRACT

Ionizable lipid nanoparticles (LNPs) pivotal to the success of COVID-19 mRNA (messenger RNA) vaccines hold substantial promise for expanding the landscape of mRNA-based therapies. Nevertheless, the risk of mRNA delivery to off-target tissues highlights the necessity for LNPs with enhanced tissue selectivity. The intricate nature of biological systems and inadequate knowledge of lipid structure-activity relationships emphasize the significance of high-throughput methods to produce chemically diverse lipid libraries for mRNA delivery screening. Here, we introduce a streamlined approach for the rapid design and synthesis of combinatorial libraries of biodegradable ionizable lipids. This led to the identification of iso-A11B5C1, an ionizable lipid uniquely apt for muscle-specific mRNA delivery. It manifested high transfection efficiencies in muscle tissues, while significantly diminishing off-targeting in organs like the liver and spleen. Moreover, iso-A11B5C1 also exhibited reduced mRNA transfection potency in lymph nodes and antigen-presenting cells, prompting investigation into the influence of direct immune cell transfection via LNPs on mRNA vaccine effectiveness. In comparison with SM-102, while iso-A11B5C1's limited immune transfection attenuated its ability to elicit humoral immunity, it remained highly effective in triggering cellular immune responses after intramuscular administration, which is further corroborated by its strong therapeutic performance as cancer vaccine in a melanoma model. Collectively, our study not only enriches the high-throughput toolkit for generating tissue-specific ionizable lipids but also encourages a reassessment of prevailing paradigms in mRNA vaccine design. This study encourages rethinking of mRNA vaccine design principles, suggesting that achieving high immune cell transfection might not be the sole criterion for developing effective mRNA vaccines.


Subject(s)
Nanoparticles , mRNA Vaccines , Muscles , Liposomes , Transfection
5.
bioRxiv ; 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37609237

ABSTRACT

Cardiovascular disease continues to take more human lives than all cancer combined, prompting the need for improved research models and treatment options. Despite a significant progress in development of mature heart-on-a-chip models of fibrosis and cardiomyopathies starting from induced pluripotent stem cells (iPSCs), human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip system with circulating immune cells to model SARS-CoV-2-induced acute myocarditis. Briefly, we observed hallmarks of COVID-19-induced myocardial inflammation in the heart-on-a-chip model, as the presence of immune cells augmented the expression levels of proinflammatory cytokines, triggered progressive impairment of contractile function and altered intracellular calcium transient activities. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the in vitro heart-on-a-chip model and then validated in COVID-19 patients with low left ventricular ejection fraction (LVEF), demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2 induced myocardial inflammation, we established that administration of human umbilical vein-derived EVs effectively rescued the contractile deficit, normalized intracellular calcium handling, elevated the contraction force and reduced the ccf- mtDNA and chemokine release via TLR-NF-kB signaling axis.

6.
Biomaterials ; 301: 122255, 2023 10.
Article in English | MEDLINE | ID: mdl-37651922

ABSTRACT

To better understand sodium channel (SCN5A)-related cardiomyopathies, we generated ventricular cardiomyocytes from induced pluripotent stem cells obtained from a dilated cardiomyopathy patient harbouring the R222Q mutation, which is only expressed in adult SCN5A isoforms. Because the adult SCN5A isoform was poorly expressed, without functional differences between R222Q and control in both embryoid bodies and cell sheet preparations (cultured for 29-35 days), we created heart-on-a-chip biowires which promote myocardial maturation. Indeed, biowires expressed primarily adult SCN5A with R222Q preparations displaying (arrhythmogenic) short action potentials, altered Na+ channel biophysical properties and lower contractility compared to corrected controls. Comprehensive RNA sequencing revealed differential gene regulation between R222Q and control biowires in cellular pathways related to sarcoplasmic reticulum and dystroglycan complex as well as biological processes related to calcium ion regulation and action potential. Additionally, R222Q biowires had marked reductions in actin expression accompanied by profound sarcoplasmic disarray, without differences in cell composition (fibroblast, endothelial cells, and cardiomyocytes) compared to corrected biowires. In conclusion, we demonstrate that in addition to altering cardiac electrophysiology and Na+ current, the R222Q mutation also causes profound sarcomere disruptions and mechanical destabilization. Possible mechanisms for these observations are discussed.


Subject(s)
Cardiomyopathy, Dilated , Induced Pluripotent Stem Cells , Adult , Humans , Myocytes, Cardiac , Cardiomyopathy, Dilated/genetics , Endothelial Cells , Lab-On-A-Chip Devices
7.
Int Immunopharmacol ; 124(Pt A): 110841, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37647682

ABSTRACT

The regulatory mechanism on granulosa cells (GCs) oxidative injury is becoming increasingly important in polycystic ovary syndrome (PCOS) studies. Serine/threonine kinase mitogen-activated protein 4 kinase 4 (Map4k4) is linked with oxidative injury and possibly associated with premature ovarian failure and ovarian dysgenesis. Herein, we investigated the function and mechanism of Map4k4 in a PCOS rat model. A microarray from GEO database identified Map4k4 was up-regulated in the ovarian of PCOS rats, and functional enrichments suggested that oxidative stress-associated changes are involved. We verified the raised Map4k4 expression in an established PCOS rat model and also in the isolated PCOS-GCs, which were consistent with the microarray data. Map4k4 knockdown in vivo contributed to regular estrous cycle, restrained steroid concentrations and ovarian injury in PCOS rats. Both Map4k4 silencing in vivo and in vitro attenuated the PCOS-related GC oxidative stress and apoptosis. Mechanically, Map4k4 activated the JNK/c-JUN signaling pathway. Importantly, a JNK agonist restored the suppressive effects of Map4k4 silencing on PCOS-induced granulosa cell injury and oxidative stress. Besides, Map4k4 may be a target gene of miR-185-5p. In conclusion, Map4k4, a potential target of miR-185-5p, is up-regulated and induces ovarian GC oxidative injury by activating JNK/c-JUN pathway in PCOS. The Map4k4/JNK/c-JUN mechanism may provide a new idea on the treatment of PCOS.

8.
Front Chem ; 10: 995261, 2022.
Article in English | MEDLINE | ID: mdl-36238104

ABSTRACT

Titanium dioxide (TiO2) has emerged as a viable choice for several biological and environmental applications because of its high efficiency, cheap cost, and high photostability. In pursuit of this purpose, the research of its many forms has been influenced by these unique aspects. The development of novel TiO2-based hybrid materials with enhanced photocatalytically induced anticancer activity has gained tremendous attention. Here, we have developed a novel photocatalytic material (TiO2-Ag NPs@-CD) by decorating ultrasmall silver nanoparticles (Ag NPs) with per-6-thio-ß-cyclodextrin (SH-ß-CD) on TiO2 NPs. TiO2-Ag NPs@-CD were characterized by employing various characterization techniques and evaluated for their anticancer activity against HeLa cancer cells using an MTT assay. The biocompatibility of the designed nanoparticles was determined on two normal cell lines, namely, 3T3 and human mesenchymal stem cells (hMSCs). The results show that the TiO2-Ag NPs@-CD induced superior cytotoxic effects on HeLa cancer cells at a concentration of 64 µg/ml. Live-dead staining and oxidative stress investigations demonstrated that cell membrane disintegration and ROS-induced oxidative stress generated by TiO2-Ag NPs@-CD inside HeLa cancer cells are the contributing factors to their exceptional anti-cancer performance. Moreover, TiO2-Ag NPs@-CD exhibited good biocompatibility with 3T3 and hMSCs. These results indicated that the combination of all three components-a silver core, SH-ß-CD ligands, and TiO2 nanoparticles-produced a synergistic anticancer effect. Hence, the TiO2-Ag NPs@-CD is a promising material that can be employed for different biological applications.

9.
Sci Rep ; 12(1): 16993, 2022 10 10.
Article in English | MEDLINE | ID: mdl-36216963

ABSTRACT

The essence of enterotypes is stratifying the entire human gut microbiome, which modulates the association between diet and disease risk. A study was designed at the Center of Reproductive Medicine, Shengjing Hospital of China Medical University and Jinghua Hospital of Shenyang. Prevotella and Bacteroides were analyzed in 407 samples of stool, including 178 men with enterotype B (61 normal, 117 overweight/obese) and 229 men with enterotype P (74 normal, 155 overweight/obese). The ratio between Prevotella and Bacteroides abundance, P/B, was used as a simplified way to distinguish the predominant enterotype. In enterotype P group (P/B ≥ 0.01), obesity was a risk factor for a reduced rate of forward progressive sperm motility (odds ratio [OR] 3.350; 95% confidence interval [CI] 1.881-5.966; P < 0.001), and a reduced rate of total sperm motility (OR 4.298; 95% CI 2.365-7.809; P < 0.001). Obesity was also an independent risk factor (OR 3.131; 95% CI 1.749-5.607; P < 0.001) after adjusting follicle-stimulating hormone. In enterotype P, body mass index, as a diagnostic indicator of a reduced rate of forward progressive sperm motility and a decreased rate of decreased total sperm motility, had AUC values of 0.627 (P = 0.001) and 0.675 (P < 0.0001), respectively, which were significantly higher than the predicted values in all patients. However, in enterotype B group (P < 0.01), obesity was not a risk factor for asthenospermia, where no significant difference between obesity and sperm quality parameters was observed. This study is tried to introduce enterotypes as a population-based individualized classification index to investigate the correlation between BMI and asthenospermia. In our study, overweight/obese men with enterotype P were found to have poorer sperm quality. however, sperm quality was not associated with overweight/obese in men with enterotype B. Thereof, BMI is a risk factor for asthenospermia only in men with enterotype P, but not in men with enterotype B.


Subject(s)
Asthenozoospermia , Obesity , Overweight , Asthenozoospermia/etiology , Bacteroides , Body Mass Index , Follicle Stimulating Hormone , Humans , Male , Obesity/complications , Obesity/epidemiology , Overweight/complications , Overweight/epidemiology , Prevotella , Semen , Sperm Motility
10.
Inorg Chem ; 61(40): 15921-15935, 2022 Oct 10.
Article in English | MEDLINE | ID: mdl-36170648

ABSTRACT

Chiral drugs are of great significance in drug development and life science because one pair of enantiomers has a different combination mode with target biological active sites, leading to a vast difference in physical activity. Metal-organic framework (MOF)-based chiral hybrid materials with specific chiral sites have excellent applications in the highly effective sensing of drug enantiomers. Sitagliptin and clonidine are effective curing drugs for controlling diabetes and hypertension, while insulin and norepinephrine are the biomarkers of these two diseases. Excessive use of sitagliptin and clonidine can cause side effects such as stomach pain, nausea, and headaches. Herein, through post-synthetic strategy, MOF-based chiral hybrid material Eu-BTB@d-carnitine (H3BTB = 1,3,5-benzenetrisbenzoic acid) was synthesized. Eu-BTB@d-carnitine has dual emission peaks at 417 and 616 nm when excited at 330 nm. Eu-BTB@d-carnitine can be applied in luminescent recognition toward sitagliptin and clonidine with high sensitivity and low detection limit (for sitagliptin detection, Ksv is 7.43 × 106 [M-1]; for clonidine detection, Ksv is 9.09 × 106 [M-1]; limit of detection (LOD) for sitagliptin is 10.21 nM, and LOD of clonidine is 8.34 nM). In addition, Eu-BTB@d-carnitine can further realize highly sensitive detection of insulin in human fluids with a high Ksv (2.08 × 106 [M-1]) and a low LOD (15.48 nM). On the other hand, norepinephrine also can be successfully discriminated by the hybrid luminescent platform of Eu-BTB@d-carnitine and clonidine with a high Ksv value of 4.79 × 106 [M-1] and a low LOD of 8.37 nM. As a result, the chiral hybrid material Eu-BTB@d-carnitine can be successfully applied in the highly effective ratiometric sensing of curing drugs and biomarkers for diabetes and hypertension.


Subject(s)
Diabetes Mellitus , Hypertension , Insulins , Metal-Organic Frameworks , Biomarkers , Carnitine , Clonidine , Europium/chemistry , Humans , Metal-Organic Frameworks/chemistry , Norepinephrine , Sitagliptin Phosphate
11.
Lab Chip ; 22(6): 1171-1186, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35142777

ABSTRACT

Coronavirus disease 2019 (COVID-19) was primarily identified as a novel disease causing acute respiratory syndrome. However, as the pandemic progressed various cases of secondary organ infection and damage by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported, including a breakdown of the vascular barrier. As SARS-CoV-2 gains access to blood circulation through the lungs, the virus is first encountered by the layer of endothelial cells and immune cells that participate in host defense. Here, we developed an approach to study SARS-CoV-2 infection using vasculature-on-a-chip. We first modeled the interaction of virus alone with the endothelialized vasculature-on-a-chip, followed by the studies of the interaction of the virus exposed-endothelial cells with peripheral blood mononuclear cells (PBMCs). In an endothelial model grown on a permeable microfluidic bioscaffold under flow conditions, both human coronavirus (HCoV)-NL63 and SARS-CoV-2 presence diminished endothelial barrier function by disrupting VE-cadherin junctions and elevating the level of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, and angiopoietin-2. Inflammatory cytokine markers were markedly more elevated upon SARS-CoV-2 infection compared to HCoV-NL63 infection. Introduction of PBMCs with monocytes into the vasculature-on-a-chip upon SARS-CoV-2 infection further exacerbated cytokine-induced endothelial dysfunction, demonstrating the compounding effects of inter-cellular crosstalk between endothelial cells and monocytes in facilitating the hyperinflammatory state. Considering the harmful effects of SARS-CoV-2 on endothelial cells, even without active virus proliferation inside the cells, a potential therapeutic approach is critical. We identified angiopoietin-1 derived peptide, QHREDGS, as a potential therapeutic capable of profoundly attenuating the inflammatory state of the cells consistent with the levels in non-infected controls, thereby improving the barrier function and endothelial cell survival against SARS-CoV-2 infection in the presence of PBMC.


Subject(s)
Angiopoietin-1 , COVID-19 Drug Treatment , COVID-19 , Endothelium, Vascular , Inflammation , SARS-CoV-2 , COVID-19/virology , Endothelial Cells/immunology , Endothelial Cells/virology , Endothelium, Vascular/immunology , Endothelium, Vascular/virology , Humans , Immunity, Innate , Inflammation/drug therapy , Inflammation/virology , Lab-On-A-Chip Devices , Leukocytes, Mononuclear
12.
J Mol Cell Cardiol ; 160: 97-110, 2021 11.
Article in English | MEDLINE | ID: mdl-34216608

ABSTRACT

Angiotensin II (Ang II) presents a critical mediator in various pathological conditions such as non-genetic cardiomyopathy. Osmotic pump infusion in rodents is a commonly used approach to model cardiomyopathy associated with Ang II. However, profound differences in electrophysiology and pharmacokinetics between rodent and human cardiomyocytes may limit predictability of animal-based experiments. This study investigates the application of an Organ-on-a-chip (OOC) system in modeling Ang II-induced progressive cardiomyopathy. The disease model is constructed to recapitulate myocardial response to Ang II in a temporal manner. The long-term tissue cultivation and non-invasive functional readouts enable monitoring of both acute and chronic cardiac responses to Ang II stimulation. Along with mapping of cytokine secretion and proteomic profiles, this model presents an opportunity to quantitatively measure the dynamic pathological changes that could not be otherwise identified in animals. Further, we present this model as a testbed to evaluate compounds that target Ang II-induced cardiac remodeling. Through assessing the effects of losartan, relaxin, and saracatinib, the drug screening data implicated multifaceted cardioprotective effects of relaxin in restoring contractile function and reducing fibrotic remodeling. Overall, this study provides a controllable platform where cardiac activities can be explicitly observed and tested over the pathological process. The facile and high-content screening can facilitate the evaluation of potential drug candidates in the pre-clinical stage.


Subject(s)
Angiotensin II/adverse effects , Cardiomyopathies/chemically induced , Cardiomyopathies/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Animals , Cardiomyopathies/pathology , Cardiotonic Agents/pharmacology , Cell Line , Cell Survival/drug effects , Coculture Techniques , Drug Evaluation, Preclinical/methods , Fibroblasts/metabolism , Fibrosis , Humans , Induced Pluripotent Stem Cells/cytology , Lab-On-A-Chip Devices , Losartan/pharmacology , Mice , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Pilot Projects , Proteome , Proteomics/methods , Recombinant Proteins/pharmacology , Relaxin/pharmacology , Ventricular Remodeling/drug effects
13.
Nat Protoc ; 16(4): 2158-2189, 2021 04.
Article in English | MEDLINE | ID: mdl-33790475

ABSTRACT

Owing to their high spatiotemporal precision and adaptability to different host cells, organ-on-a-chip systems are showing great promise in drug discovery, developmental biology studies and disease modeling. However, many current micro-engineered biomimetic systems are limited in technological application because of culture media mixing that does not allow direct incorporation of techniques from stem cell biology, such as organoids. Here, we describe a detailed alternative method to cultivate millimeter-scale functional vascularized tissues on a biofabricated platform, termed 'integrated vasculature for assessing dynamic events', that enables facile incorporation of organoid technology. Utilizing the 3D stamping technique with a synthetic polymeric elastomer, a scaffold termed 'AngioTube' is generated with a central microchannel that has the mechanical stability to support a perfusable vascular system and the self-assembly of various parenchymal tissues. We demonstrate an increase in user familiarity and content analysis by situating the scaffold on a footprint of a 96-well plate. Uniquely, the platform can be used for facile connection of two or more tissue compartments in series through a common vasculature. Built-in micropores enable the studies of cell invasion involved in both angiogenesis and metastasis. We describe how this protocol can be applied to create both vascularized cardiac and hepatic tissues, metastatic breast cancer tissue and personalized pancreatic cancer tissue through incorporation of patient-derived organoids. Platform assembly to populating the scaffold with cells of interest into perfusable functional vascularized tissue will require 12-14 d and an additional 4 d if pre-polymer and master molds are needed.


Subject(s)
Blood Vessels/physiology , Lab-On-A-Chip Devices , Organoids/physiology , Perfusion , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Tissue Scaffolds/chemistry
14.
Exp Ther Med ; 21(5): 424, 2021 May.
Article in English | MEDLINE | ID: mdl-33747163

ABSTRACT

The present study was designed to investigate the role and mechanism of action behind the action of lidocaine in gastric cancer cells. Lidocaine was tested for its potential role in affecting the viability of cells using Cell Counting Kit-8 (CCK-8) assays. It was found that there was a decreased MKN45 cell viability upon lidocaine treatment in a dose-dependent manner. Phosphorylated c-Met, phosphorylated c-Src, c-Met and c-Src levels were detected using western blotting following lidocaine or hepatocyte growth factor (HGF) intervention. It was found that the phosphorylation levels of c-Met and c-Src were markedly reduced by lidocaine treatment, with this effect being further relieved by the addition of HGF. Subsequently, whether lidocaine repressed the malignant biological properties of gastric cancer cells through the c-Met/c-Src axis was further investigated through the detection of epithelial-mesenchymal transition markers (N-caderin and vimentin), wound healing and transwell assay analysis. In addition, cell apoptosis and the levels of apoptosis-related proteins were determined using TUNEL and western blot assays, respectively. The results demonstrated that the malignant behavior of cells were notably repressed upon lidocaine treatment, but the addition of HGF markedly reversed these effects, indicating that the effects of lidocaine on supressing the malignant behaviour of cells could be mediated through the c-Met/c-Src axis. Subsequently, whether lidocaine affected the sensitivity of cells to cisplatin or 5-FU was analyzed using a CCK-8 assay. Enhanced sensitivity of cells to cisplatin or 5-FU was observed when treated in combination with lidocaine. The present study concluded that the involvement of the c-Met/c-Src pathway in the biological behaviour of MKN45 cells was mediated by lidocaine. Therefore, lidocaine may have the potential to suppress the malignant behaviour and proliferation of gastric cancer cells.

15.
Environ Sci Pollut Res Int ; 28(29): 39101-39109, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33745054

ABSTRACT

There is limited and equivocal epidemiological evidence relating to the association between maternal sulfur dioxide (SO2) exposure and the risk of oral clefts (OCs) in offspring. We performed a population-based case-control study in Liaoning province to evaluate aforementioned relationship during 3 months before conception, the first trimester of pregnancy, and their single months. The study involved 3086 patients with OCs and 7950 controls. Data relating to SO2 concentration was acquired from air monitoring stations throughout the study period. We used a multivariable logistic regression model to evaluate the association between exposure to SO2 and the risk of OCs during the exposure windows. Maternal SO2 exposure was positively related to OCs during the 3 months before conception (odds ratio = 1.38, 95% confidence interval: 1.15-1.65; P for trend < 0.01). Positive relationships were obtained from the first and second months before conception and the first month of pregnancy. Thus, our research reflects a relationship between SO2 exposure and the risk of OCs. Future studies are now required to verify the association between SO2 exposure and OCs during pregnancy and indicate the most relevant vulnerable exposure time windows.


Subject(s)
Air Pollutants , Air Pollution , Cleft Palate , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/analysis , Case-Control Studies , China/epidemiology , Cleft Palate/chemically induced , Cleft Palate/epidemiology , Female , Humans , Maternal Exposure/adverse effects , Nitrogen Dioxide , Particulate Matter/analysis , Pregnancy , Sulfur Dioxide
16.
Bioact Mater ; 6(9): 2801-2819, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33665510

ABSTRACT

Despite showing a great promise in the field of nanomedicine, nanoparticles have gained a significant attention from regulatory agencies regarding their possible adverse health effects upon environmental exposure. Whether those nanoparticles are generated through intentional or unintentional means, the constant exposure to nanomaterials can inevitably lead to unintended consequences based on epidemiological data, yet the current understanding of nanotoxicity is insufficient relative to the rate of their emission in the environment and the lack of predictive platforms that mimic the human physiology. This calls for a development of more physiologically relevant models, which permit the comprehensive and systematic examination of toxic properties of nanoparticles. With the advancement in microfabrication techniques, scientists have shifted their focus on the development of an engineered system that acts as an intermediate between a well-plate system and animal models, known as organ-on-a-chips. The ability of organ-on-a-chip models to recapitulate in vivo like microenvironment and responses offers a new avenue for nanotoxicological research. In this review, we aim to provide overview of assessing potential risks of nanoparticle exposure using organ-on-a-chip systems and their potential to delineate biological mechanisms of epidemiological findings.

17.
Aging (Albany NY) ; 13(6): 8865-8879, 2021 03 19.
Article in English | MEDLINE | ID: mdl-33742607

ABSTRACT

BACKGROUND: The findings of associations between prenatal air pollution exposure and hypospadias risk in offspring are inconsistent. No systematic review or meta-analysis has yet summarized the present knowledge on the aforementioned topic. METHODS: Relevant manuscripts were identified by searching PubMed and Web of Science databases through January 31, 2020. Summary odds ratios (ORs) with 95% confidence intervals (CIs) in meta-analyses were estimated based on a random effects model. Publication bias was evaluated by funnel plots, Begg's test, and Egger's test. RESULTS: The search identified 3,032 relevant studies. Sixteen studies cumulatively involving 21,701 hypospadias cases and 1,465,364 participants were included. All of these studies were classified as having a low risk of bias. We classified pollutants as nitrogen oxides, particulate matter (PM), ozone, and other exposures. The exposure window to pollutants varied from three months before conception to seven days after delivery. In the meta-analyses, only PM2.5 exposure in the first trimester was related to increased risk of hypospadias (per 10 µg/m3 OR = 1.34; 95% CI: 1.06-1.68). CONCLUSION: We found evidence for an effect of PM2.5 exposure on hypospadias risk. Improvements in the areas of study design, exposure assessment, and specific exposure window are needed to advance this field.


Subject(s)
Air Pollution/adverse effects , Environmental Exposure/adverse effects , Hypospadias/etiology , Particulate Matter/adverse effects , Female , Humans , Male , Pregnancy
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 249: 119214, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33257240

ABSTRACT

In industry, over usage of Cu2+ and Al3+ will lead to toxic wastewater, which further to give serious pollution for the environment. On the other hand, L-lysine can enhance serotonin release in the amygdala, with subsequent changes in psychobehavioral responses to stress. Therefore it is the urgent problem to design a method for detecting the amount of Cu2+, Al3+, and L-lysine. In this work, through the solvothermal synthesis method, two new coordination complexes based on the new bifunctional building block 4'-(1H-1,2,4-triazole-1-yl)- [1,1'-biphenyl]-4-carboxylic acid (HL) have been synthesized, namely, [Zn(L)2·4H2O] (complex 1) and [Cd(L)2·4H2O] (complex 2). X-ray single-crystal diffractometer was used to analyze its structure, powder X-ray diffraction (PXRD) patterns confirmed that 1 and 2 powder's purity and 1 can keep stable during the detection process of Cu2+, Al3+, and L-lysine, respectively. Elemental analysis, thermogravimetric analysis, infrared analysis, ultraviolet analysis and fluorescent spectrum have been used to characterize these complexes. The photo-luminescent test showed that 1 can accurately recognize Al3+ and Cu2+ among various cations. On the other hand, 1 can distinguish L-lysine among amino acid molecules. Therefore, 1 can be utilized as a multifunctional fluorescent probe for Al3+(Ksv = 1.5570 × 104 [M]-1), Cu2+(Ksv = 1.4948 × 104 [M]-1) and L-lysine (Ksv = 4.9118 × 104 [M]-1) with low detection limits (17.5 µM, 18.2 µM, 5.6 µM) respectively.


Subject(s)
Coordination Complexes , Cadmium , Copper , Crystallography, X-Ray , Lysine , Zinc
20.
ACS Cent Sci ; 6(6): 903-912, 2020 Jun 24.
Article in English | MEDLINE | ID: mdl-32607437

ABSTRACT

Kidney-on-a-chip devices may revolutionize the discovery of new therapies. However, fabricating a 3D glomerulus remains a challenge, due to a requirement for a microscale soft material with complex topography to support cell culture in a native configuration. Here, we describe the use of microfluidic spinning to recapitulate complex concave and convex topographies over multiple length scales, required for biofabrication of a biomimetic 3D glomerulus. We produced a microfluidic extruded topographic hollow fiber (h-FIBER), consisting of a vessel-like perfusable tubular channel for endothelial cell cultivation, and a glomerulus-like knot with microconvex topography on its surface for podocyte cultivation. Meter long h-FIBERs were produced in microfluidics within minutes, followed by chemically induced inflation for generation of topographical cues on the 3D scaffold surface. The h-FIBERs were assembled into a hot-embossed plastic 96-well plate. Long-term perfusion, podocyte barrier formation, endothelialization, and permeability tests were easily performed by a standard pipetting technique on the platform. Following long-term culture (1 month), a functional filtration barrier, measured by the transfer of albumin from the blood vessel side to the ultrafiltrate side, suggested the establishment of an engineered glomerulus.

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