Effects of environmental phenols on eGFR: machine learning modeling methods applied to cross-sectional studies.

Purpose: Limited investigation is available on the correlation between environmental phenols' exposure and estimated glomerular filtration rate (eGFR). Our target is established a robust and explainable machine learning (ML) model that associates environmental phenols' exposure with eGFR. Methods: Our datasets for constructing the associations between environmental phenols' and eGFR were collected from the National Health and Nutrition Examination Survey (NHANES, 2013-2016). Five ML models were contained and fine-tuned to eGFR regression by phenols' exposure. Regression evaluation metrics were used to extract the limitation of the models. The most effective model was then utilized for regression, with interpretation of its features carried out using shapley additive explanations (SHAP) and the game theory python package to represent the model's regression capacity. Results: The study identified the top-performing random forest (RF) regressor with a mean absolute error of 0.621 and a coefficient of determination of 0.998 among 3,371 participants. Six environmental phenols with eGFR in linear regression models revealed that the concentrations of triclosan (TCS) and bisphenol S (BPS) in urine were positively correlated with eGFR, and the correlation coefficients were ß = 0.010 (p = 0.026) and ß = 0.007 (p = 0.004) respectively. SHAP values indicate that BPS (1.38), bisphenol F (BPF) (0.97), 2,5-dichlorophenol (0.87), TCS (0.78), BP3 (0.60), bisphenol A (BPA) (0.59) and 2,4-dichlorophenol (0.47) in urinary contributed to the model. Conclusion: The RF model was efficient in identifying a correlation between phenols' exposure and eGFR among United States NHANES 2013-2016 participants. The findings indicate that BPA, BPF, and BPS are inversely associated with eGFR.

Rapid heating (<2 Ma) to ultrahigh-temperature metamorphism via asthenospheric upwelling.

Ultrahigh-temperature (UHT) metamorphism is the most thermally extreme form of regional crustal metamorphism, with temperatures exceeding 900°C. The duration and heat source of UHT metamorphism are critical constraints on the tectonic evolution of orogenic systems. Here, we report the discovery of a sapphirine-bearing granulite from the east-central Himalaya which preserves UHT evidence. The reconstructed pressure-temperature-time path indicates that the temperature increased by almost 200°C within ~2 Ma which is consistent with rapid asthenospheric heat input. Numerical simulations illustrate potential mechanisms for such heating: juxtaposition of the deep crustal accretionary system with the upwelling asthenospheric mantle through newly developed apertures generated by slab break-off and/or associated vertical tearing of down-going Indian lithosphere. Spatial-temporal consistencies among the UHT metamorphic phases, postcollisional magmatism, geophysical constraints, and crustal deformation indicate that slab break-off or tearing controls broad swaths of Himalayan tectonics. The consequent upwelling asthenosphere may have been a significant heat source for the Miocene Himalaya and for similar ancient collisional orogenic systems.

The role of extended synaptotagmin at membrane contact sites in cancer research.

Membrane contact sites (MCSs) are adjacent locations between the membranes of two different organelles and play important roles in various physiological processes, including cellular calcium and lipid signaling. In cancer research, MCSs have been proposed to regulate tumor metabolism and fate, contributing to tumor progression, and this function could be exploited for tumor therapy. However, there is little evidence on how MCSs are involved in cancer progression. In this review, we use extended synaptotagmins (E-Syts) as an entry point to describe how MCSs affect cancer progression and may be used as new diagnostic biomarkers. We then introduced the role of E-Syt and its related pathways in calcium and lipid signaling, aiming to explain how MCSs affect tumor proliferation, progression, metastasis, apoptosis, drug resistance, and treatment through calcium and lipid signaling. Generally, this review will facilitate the understanding of the complex contact biology of cancer cells.

Total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert II AEG.

PURPOSE: The optimal procedure is still controversial about Siewert type II AEG, We are attempt to explore the efficacy and feasibility of total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis for Siewert type II AEG. METHOD: Data of patients with Siewert type II AEG who received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis in the Hebei General Hospital were collected from October 2020 to October 2021, The operation time, surgical blood loss, the number of dissected lymph nodes, duration of drainage tube, the length of stay in ICU, the resume oral feeding time, the length of postoperative hospital stay, postoperative complications and other related indicators of the patients were collected to evaluate the safety and feasibility of this operation. RESULT: A total of 17 patients received total laparoscopic total gastrectomy and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosisin the treatment of Siewert type II AEG were analyzed in our research. The mean operation time was 253 ± 24.8 min (196-347 min); The median surgical blood loss was 250 ml (20-2400 ml); The average number of dissected lymph nodes were 28 ± 4.6 (17-36); The median duration of drainage tube was 5 days (3-7days); The median length of stay in ICU was 18 h(10-34 h); The median time of resume oral feeding was 6 days (5-7days); The median postoperative hospital stay was 11 days (8-15 days). Among the all enrolled patients, one patient underwent the conversion to laparotomy due to the massive intraoperative bleeding, one patient developed anastomotic stenosis at jejunum side-to-side anastomosis on the first month after surgery, there was no case of death during the operation and postoperative anastomotic fistula. All patients achieved R0 resection with an average distance of 6 cm (4-8.5 cm) from the upper margin of the tumor to the resection margin. CONCLUSION: The operation of total laparoscopic total gastric and distal esophagectomy combined with reconstruction by transhiatal esophagojejunal Roux-en-y mediastinal anastomosis is technically feasible and sufficiently safe in the treatment of Seiwert type II AEG from our primary clinical experience. This procedure could be one of the alternatives for the radical treatment of Siewert type II AEG.

Purely nonlinear amplified ultralow-noise transmission using hybrid second-order DRA and PPLN-based PSA.

We report ultralow-noise transmission over a 102-km single-mode fiber using a purely nonlinear amplification scheme consisting of a second-order distributed Raman amplifier (DRA) and a phase-sensitive amplifier (PSA) based on periodically poled LiNbO3 waveguides. The hybrid DRA/PSA features a broadband gain over the C and L bands and an ultralow-noise advantage, with a less than -6.3 dB effective noise figure in the DRA stage and a 1.6 dB optical signal-to-noise ratio (OSNR) improvement in the PSA stage. Compared with the unamplified link, the OSNR is improved by 10.2 dB for a 20-Gbaud 16QAM signal in the C band, resulting in error-free detection (a bit-error rate of less than 3.8 × 10-3) for the signal with a low link input power of -25 dBm. Mitigation of nonlinear distortion is also achieved by the proposed nonlinear amplified system due to the subsequent PSA.

Genome-wide identification of WOX family members in nine Rosaceae species and a functional analysis of MdWOX13-1 in drought resistance.

WUSCHEL-related homeobox (WOX) transcription factors (TFs) are important in plant development processes and evolutionary novelties. In this study, a genome-wide comprehensive analysis of WOX genes from nine Rosaceae species was carried out, and their potential roles in Malus were subsequently investigated. 125 WOXs in 9 Rosaceae species were identified and classified into three clades, i.e., the ancient, intermediate, and WUS clades. Prunus. domestica contained the most intra-genomic collinearity among the nine Rosaceae species. Additionally, the cis-elements in WOX gene family members were compared and classified into three categories, including phytohormone-responsive, plant growth and development, and abiotic and biotic stresses. Overexpression (OE) of MdWOX13-1 also increased the callus weight and enhanced ROS scavenging against drought stress. Furthermore, via yeast-one hybrid assay and LUC analyses, MdWOX13-1 could directly bind to the MdMnSOD promoter. Therefore, our results will facilitate further study of the WOX genes' function in the Rosaceae family.

Kukoamine A activates Akt/GSK-3ß signaling pathway to inhibit oxidative stress and relieve myocardial ischemia-reperfusion injury.

PURPOSE: Myocardial ischemia/reperfusion (MI/R) injury refers to a pathological condition of treatment of myocardial infarction. Oxidative stress and inflammation are believed to be important mechanisms mediating MI/R injury. Kukoamine A (KuA), a sperm, is the main bioactive component extracted from the bark of goji berries. In this study, we wanted to investigate the possible effects of KuA on MI/R injury. METHODS: In this experiment, all rats were divided into sham operation group, MI/R group, KuA 10 mg + MI/R group, KuA 20 mg + MI/R group. After 120 min of ischemia/reperfusion treatment, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal rates of rising and fall of left ventricular pressure (±dp/dtmax), and ischemic area were detected. Serum samples of rats in each group were collected. The enzyme activities of catalase (CAT), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), levels of malondialdehyde (MDA), CK muscle/brain (CK-MB), tumor necrosis factor (TNF), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were detected using enzyme-linked immunosorbent assay (ELISA). The apoptosis of myocardium in each group was detected according to the instructions of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of mammalian target of glycogen synthase kinase-3ß (GSH-3ß) and protein kinase B (Akt) mRNA level in myocardial tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: MI/R rats showed a significant increase in oxidative stress and inflammation. In addition, we showed that KuA significantly improved the myocardial function such as LVSP, left ventricular ejection fraction, +dp/dt, and -dp/dt. Here, it attenuated dose-dependent histological damage in ischemia-reperfused myocardium, which is associated with the enzyme activities of SOD, GSH-PX, and levels of MDA, IL-6, TNF-α, L-1ß. CONCLUSIONS: KuA inhibited gene expression of Akt/GSK-3ß, inflammation, oxidative stress and improved MR/I injury. Taken together, our results allowed us to better understand the pharmacological activity of KuA against MR/I injury.

Effect and mechanisms of synthesis conditions on the cadmium adsorption capacity of modified fly ash.

In this study, modified coal fly ash (NMFA) was prepared by sodium hydroxide (NaOH) with low-temperature hydrothermal method. The differences of the ash to alkali mass ratio (5:3, 5:4, 5:5, 5:6), calcination temperature (100 â„ƒ, 200 â„ƒ, 300 â„ƒ), and calcination time (1 h, 3 h, 5 h) were investigated. The adsorption experiments obtained the optimal result with the ash to base ratio of 5:5, calcination temperature of 200 â„ƒ, and calcination time of 3 h, adsorbing 90.27 mg/g of Cd2+. The characterization results (SEM-EDS, FTIR, XRD, and XPS) also confirmed the effective adsorption of Cd2+ by NMFA. The functional groups of Si-O, Al-O, and Fe-O played an important role in Cd2+ removal. Meanwhile, the influences of dosage, different pH, and co-existing cations were also investigated. Quasi-secondary adsorption kinetics and Langmuir isotherm model were also referred to the Cd2+ adsorption by NMFA. Therefore, the good adsorption of NMFA-3 on Cd2+ provided new ideas for the safe utilization of fly ash and heavy metal purification in wastewater.

Which Is the Most Appropriate PI3K Inhibitor for Breast Cancer Patients with or without PIK3CA Status Mutant? A Systematic Review and Network Meta-Analysis.

OBJECTIVE: The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a promising treatment target for patients with breast cancer (BC). Our study aimed to evaluate the most effective and safe PI3K inhibitor for patients with BC, especially in PIK3CA mutation. METHODS: Electronics databases were systematically searched from their inception to June 2020 for published randomized controlled trials (RCTs) comparing PI3K inhibitor therapy versus non-PI3K inhibitor therapy in patients with BC that mentioned or reported data of PIK3CA-mutated patient subgroups. Eligible RCTs had to report at least one of the following clinical outcomes: objective response rate (ORR), progression-free survival (PFS), or adverse events (AE). RESULTS: Nine eligible RCTs involving 3872 BC patients and four PI3K inhibitor therapy arms (i.e., alpelisib, buparlisib, pictilisib, and taselisib) were included. In evaluating ORR, beneficial significant results of PI3K inhibitors could be found in the PIK3CA mutated group (1.952, 1.012 to 3.766); analogous results could also be found in 6m-PFS (1.519, 1.144 to 2.018) and PFS from HR data (-0.346, -0.525 to -0.168). From pairwise and network meta-analyses, buparlisib showed the most favorable ORR, as it was significantly different from fulvestrant in the PIK3CA-mutated patient group (2.80, 1.56 to 5.03). Alpelisib ranked first in the assessment of 6m-PFS and was significantly different from fulvestrant in the PIK3CA-mutated group (2.33, 1.45 to 3.44). The above PI3K inhibitors had good safety with few serious AEs. PROSPERO registration CRD42020193932. CONCLUSION: The PI3K inhibitors alpelisib and buparlisib appear to have superior efficacy and safety therapeutic choices for patients with BC, especially in PIK3CA-mutated patients.

Synthesis and Identification of a Novel Peptide, Ac-SDK (Biotin) Proline, That Can Elicit Anti-Fibrosis Effects in Rats Suffering from Silicosis.

BACKGROUND: N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a short peptide with an anti-silicosis effect. However, the short biological half-life and low plasma concentration of Ac-SDKP hamper discovery of specific targets in organisms and reduce the anti-silicosis effect. A novel peptide, Ac-SDK (biotin) proline, termed "Ac-B", with anti-fibrotic properties was synthesized. METHODS: Ac-B was detected quantitatively by high-performance liquid chromatography. Phagocytosis of Ac-B by the alveolar epithelial cell line A549 was investigated by confocal laser scanning microscopy and flow cytometry. To further elucidate the cellular-uptake mechanism of Ac-B, chemical inhibitors of specific uptake pathways were used. After stimulation with transforming growth factor-ß1, the effects of Ac-B on expression of the myofibroblast marker vimentin and accumulation of collagen type I in A549 cells were analyzed by Western blotting. Sirius Red staining and immunohistochemical analyses of the effect of Ac-B on expression of α-smooth muscle actin (SMA) in a rat model of silicosis were undertaken. RESULTS: Ac-B had good traceability during the uptake, entry, and distribution in cells. Ac-B treatment prevented an increase in α-SMA expression in vivo and in vitro and was superior to that of Ac-SDKP. Caveolae-mediated uptake of Ac-B by A549 cells led to achieving anti-epithelial-mesenchymal transformation (EMT) effects. CONCLUSION: Ac-B had an anti-fibrotic effect and could be a promising agent for the fibrosis observed in silicosis in the future.

Exploration and analysis of the value of tumor-marker joint detection in the pathological type of lung cancer.

Lung cancer is a disease characterized by the uncontrolled growth of cells in lung tissue. If left untreated, cell growth can spread beyond the lungs to a process called metastasis and reach surrounding tissues or other organs. This experiment was set up to discuss and analyze the research value of joint detection of tumor markers including carcino-embryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21-1) and neuron-specific enolase (NSE) in the diagnosis and pathological type of lung cancer. From November 2016 to February 2018, 378 cases of patients with lung cancer treated in our hospital and 200 cases of people with healthy physical examinations were collected. The electrochemical immunoluminescence method was adopted to detect the CEA, CYFRA21-1 and NSE. The detected positive rate and the concentration of CEA, CYFRA21-1 and NSE of lung cancer group were higher than that of the healthy physical examination group. The differences were of statistical significance (P<0.05); the detected positive rate of CEA and CYFRA21-1 and the concentration of CEA, CYFRA21-1 and NSE of squamous carcinoma group were higher than that of the adenocarcinoma group. The differences were of statistical significance (P<0.05). The CEA, CYFRA21-1 and NSE are related to the pathological type of lung cancer and can be regarded as related indicators to diagnose lung cancer.

Possibility of removing cadmium pollution from the environment using a newly synthesized material coal fly ash.

Coal fly ash (FA) is a solid waste produced in coal combustion. This study focused on the removal of Cd2+ from wastewater by a newly synthesized adsorbent material, the low-temperature and sodium hydroxide-modified fly ash (SHM-FA). The SEM and BET analyses of SHM-FA demonstrated that the adsorbent was porous and had a huge specific surface area. The XRF, XRD, FTIR and TGA characterization showed that SHM-FA has an amorphous structure and the Si-O and Al-O in the fly ash dissolved into the solution, which improved the adsorption capacity of Cd. The results indicated that SHM-FA has desired adsorption performance. The adsorption performance was significantly affected by the dosage, starting pH, Cd2+ initial concentrations, and temperature, as well as adsorption time. In the optimal conditions, the removal efficiency and adsorption capacity of Cd2+ by SHM-FA were 95.76% and 31.79 mg g-1, respectively. The experiment provided clearly explained adsorption kinetics and isotherms. And the results confirmed that the adsorption behavior was well described by the pseudo-second-order kinetic and Langmuir isotherm model, which means that the adsorption of Cd2+ was controlled by SHM-FA through surface reaction and external diffusion process. In addition, the recycling of SHM-FA for reuse after Cd2+ adsorption showed high removal efficiency up to six times of use. Therefore, it can be concluded that SHM-FA is a low-cost adsorbent for Cd2+ removal from wastewater.

Potential of removing Cd(II) and Pb(II) from contaminated water using a newly modified fly ash.

Modified fly ash was prepared through low-temperature roasting method using NaOH as activator. The techniques of Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray photoelectron spectroscopy (XPS) and the X-ray diffraction (XRD) were introduced to analyze the chemical and physical performance of samples, respectively. It was found that a significant improvements in activity and specific surface area of adsorbent. This work systematically reported the uptake performances of modified materials for single and two mixed toxic cations Pb(II) and Cd(II). The results unveiled that pseudo-second-order model was suitable to analyze the adsorption process. The adsorption process were better fitted by Langmuir model and the maximum uptake capacities were 126.55 and 56.31 mg g-1 for Pb(II) and Cd(II) in single system at 298 K, respectively. Additionally, in mixed solution, the maximum uptake capacity reduced to 120.48 and 36.10 mg g-1 under the same adsorption conditions. Competitive adsorption results demonstrated that adsorption ability was restricted by other metal ions, as while as, the binding affinity of two cations followed the order of Pb(II)>Cd(II). Meanwhile, the co-existed cations as Ca(II), Mg(II) Na(I) and K(I) had antagonistic effects on the uptake of Cd(II) and Pb(II). The results indicate that the modified fly ash was a low-cost and effective adsorbent for the cleaning up metal ions in wastewater, which has a promising application prospect.

The Effect of Intensive Statin Therapy on Symptomatic Intracranial Arterial Stenosis.

BACKGROUND: The aim of this study was to observe the effect of intensive statin therapy on symptomatic intracranial arterial stenosis. METHODS: overall, 120 patients with symptomatic intracranial arterial stenosis were admitted to the Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China from January 2010 to May 2013. They were randomly divided into three groups and were given different doses of atorvastatin orally for 1 year or more, and followed up for 12 months. The three groups were assessed for clinical end-point event rates and changes in cerebral blood flow value before and after treatment to assess the effectiveness of intensive statin therapy. RESULTS: The incidence rates of end-point cerebrovascular events in the low-dose group (10 mg/d), the general-dose group (20 mg/d) and the intensive treatment group (40 mg/d) were 26.3%, 13.5% and 5.4% respectively during the 12-month follow-up after treatment. There was a significant difference between the low dose group and the intensive treatment group (P<0.05). The relative cerebral blood flow and relative cerebral blood volume of the three groups were significantly higher than those before treatment (P<0.05), and the relative time to peak for the intensive treatment group was shorter than that before treatment (P<0.001). CONCLUSION: Atorvastatin at 40 mg/d has a significant advantage compared with atorvastatin at 20 mg/d and 10 mg/d in reducing cerebrovascular events and improving cerebral blood flow.

Establishment of flail chest in a rabbit model / 中国胸心血管外科临床杂志

@#Objective    To explore the feasibility of establishing a rabbit model of flail chest. Methods    Flail chest model was eatablished in 12 New Zealand white rabbits after anesthesia and sterile surgery. The paradoxical movement of chest wall was recorded by the biological signal acquisition system, arterial blood was collected for blood gas analysis, the vital signs were recorded by electrocardiogram (ECG) and the lung tissue was taken for the pathological analysis at the end of the experiment. The effect of flail chest on the respiratory function of experimental animals was analyzed to evaluate the feasibility of establishing flail chest model. Results    All surgeries were successful without mortality. The operation time was 41.42±7.08 min. Duration of endotracheal intubation was 79.33±12.21 min. Statistical results showed that the pH, partial pressure of arterial carbon dioxide (PaCO2) and base excess (BE) increased; while partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) reduced. Pathological results showed that flail chest not intervented for a long period would lead to organic lesions. Conclusion    The rabbit model of flail chest is feasible, safe, repeatable, easy and simple to handle. The animal is easy to access which is the foundation to study the disease process, recovery procedure and the efficacy after intervention.

Differential gene expression analysis in glioblastoma cells and normal human brain cells based on GEO database.

The differentially expressed genes between glioblastoma (GBM) cells and normal human brain cells were investigated to performed pathway analysis and protein interaction network analysis for the differentially expressed genes. GSE12657 and GSE42656 gene chips, which contain gene expression profile of GBM were obtained from Gene Expression Omniub (GEO) database of National Center for Biotechnology Information (NCBI). The 'limma' data packet in 'R' software was used to analyze the differentially expressed genes in the two gene chips, and gene integration was performed using 'RobustRankAggreg' package. Finally, pheatmap software was used for heatmap analysis and Cytoscape, DAVID, STRING and KOBAS were used for protein-protein interaction, Gene Ontology (GO) and KEGG analyses. As results: i) 702 differentially expressed genes were identified in GSE12657, among those genes, 548 were significantly upregulated and 154 were significantly downregulated (p<0.01, fold-change >1), and 1,854 differentially expressed genes were identified in GSE42656, among the genes, 1,068 were significantly upregulated and 786 were significantly downregulated (p<0.01, fold-change >1). A total of 167 differentially expressed genes including 100 upregulated genes and 67 downregulated genes were identified after gene integration, and the genes showed significantly different expression levels in GBM compared with normal human brain cells (p<0.05). ii) Interactions between the protein products of 101 differentially expressed genes were identified using STRING and expression network was established. A key gene, called CALM3, was identified by Cytoscape software. iii) GO enrichment analysis showed that differentially expressed genes were mainly enriched in 'neurotransmitter:sodium symporter activity' and 'neurotransmitter transporter activity', which can affect the activity of neurotransmitter transportation. KEGG pathway analysis showed that the differentially expressed genes were mainly enriched in 'protein processing in endoplasmic reticulum', which can affect protein processing in endoplasmic reticulum. The results showed that: i) 167 differentially expressed genes were identified from two gene chips after integration; and ii) protein interaction network was established, and GO and KEGG pathway analyses were successfully performed to identify and annotate the key gene, which provide new insights for the studies on GBN at gene level.

Gene Expression Profile of Peripheral Blood Mononuclear Cells in Response to Intracerebral Hemorrhage.

RNA-sequencing, a powerful tool, yields a comprehensive view of whole transcriptome. Intracerebral hemorrhage (ICH) is a devastating form of stroke. To date, RNA-sequencing analysis of ICH has not been reported. Peripheral blood mononuclear cells (PBMCs) were used as a source of mRNA for gene expression profile analysis in stroke. In this study, we performed transcriptome analyses for PBMCs from four ICH patients and four healthy volunteers on Illumina platform. We identified 4040 significantly differentially expressed genes (DEGs). Functional annotation of DEGs with DAVID Bioinformatics Resources indicated that genes associated with cell apoptosis, autophagy, cell-cell adhesion, inflammatory response, protein binding, positive regulation of gene expression, and signal transduction were most significantly enriched by DEGs. Gene set enrichment analysis identified 40 significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including chemokine signaling, cytokine-cytokine receptor interaction, oxidative phosphorylation, and glutathione metabolism processes. These data point to a complex mechanism for ICH pathogenesis. Overall, the present study demonstrated an altered gene expression profile of PBMCs in response to acute ICH. Our study provided important information for understanding the molecular mechanisms of ICH pathogenesis at system-wide levels.

Obeticholic Acid Protects against Lipopolysaccharide-Induced Fetal Death and Intrauterine Growth Restriction through Its Anti-Inflammatory Activity.

Farnesoid X receptor (FXR) is expressed in human and rodent placentas. Nevertheless, its function remains obscure. This study investigated the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, on LPS-induced fetal death and intrauterine growth restriction. All pregnant mice except controls were i.p. injected with LPS (100 µg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD13 to GD17. As expected, placental FXR signaling was activated by OCA. OCA pretreatment protected against LPS-induced fetal death. In addition, OCA pretreatment alleviated LPS-induced reduction of fetal weight and crown-rump length. Additional experiments showed that OCA inhibited LPS-evoked TNF-α in maternal serum and amniotic fluid. Moreover, OCA significantly attenuated LPS-induced upregulation of placental proinflammatory genes including Tnf-α, Il-1ß, IL-6, Il-12, Mip-2, Kc, and Mcp-1 By contrast, OCA elevated anti-inflammatory cytokine IL-10 in maternal serum, amniotic fluid, and placenta. Further analysis showed that OCA blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth zone. These results provide a mechanistic explanation for placental FXR-mediated anti-inflammatory activity. Overall, this study provides evidence for roles of FXR as an important regulator of placental inflammation.

Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport.

Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl2 (2.5 or 5.0mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl2. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters.