Short-term exposures to PM2.5, PM2.5 chemical components, and antenatal depression: Exploring the mediating roles of gut microbiota and fecal short-chain fatty acids.

BACKGROUND: PM2.5 and its chemical components increase health risks and are associated with depression and gut microbiota. However, there is still limited evidence on whether gut microbiota and short-chain fatty acids (SCFAs) mediate the association between PM2.5, PM2.5 chemical components, and antenatal depression. The purpose of this study was to investigate the mediating role of maternal gut microbiota in correlations between short-term exposure to PM2.5, short-term exposure to PM2.5 chemical components, and antenatal depression. METHODS: Demographic information and stool samples were collected from 75 pregnant women in their third trimester. Their exposure to PM2.5 and PM2.5 chemical components was measured. Participants were divided into the non-antenatal depression group or the antenatal depression group according to the cut-off of 10 points on the Edinburgh Postnatal Depression Scale (EPDS). The gut microbiota were analyzed using the 16 S rRNA-V3/V4 gene sequence, and the concentration of PM2.5 and its chemical components was calculated using the Tracking Air Pollution in China (TAP) database. Gas chromatography-mass spectrometry was used to analyze SCFAs in stool samples. In order to assess the mediating effects of gut microbiota and SCFAs, mediation models were utilized. RESULTS: There were significant differences between gut microbial composition and SCFAs concentrations between the non-antenatal depression group and the antenatal depression group. PM2.5 and its chemical components were positively associated with EPDS scores and negatively associated with genera Enterococcus and Enterobacter. Genera Candidatus_Soleaferrea (ß = -7.21, 95%CI -11.00 to -3.43, q = 0.01) and Enterococcus (ß = -2.37, 95%CI -3.87 to -0.87, q = 0.02) were negatively associated with EPDS scores, indicating their potential protective effects against antenatal depression. There was no significant association between SCFAs and EPDS scores. The mediating role of Enterococcus between different lagged periods of PM2.5, PM2.5 chemical component exposure, and antenatal depression was revealed. For instance, Enterococcus explained 29.23% (95%CI 2.16-87.13%, p = 0.04) of associations between PM2.5 exposure level at the day of sampling (lag 0) and EPDS scores. CONCLUSION: Our study highlights that Enterococcus may mediate the associations between PM2.5, PM2.5 chemical components, and antenatal depression. The mediating mechanism through which the gut microbiota influences PM2.5-induced depression in pregnant women still needs to be further studied.

Postnatal nighttime light exposure and infant temperament at age 12 months: mediating role of genus Akkermansia.

The gut microbiome has been reported to be associated with nighttime light (NTL) exposure and temperament. However, the specific role of infant gut microbiome plays in NTL exposure and temperament is unclear. This study investigated the potential mediating role of infants' gut microbiome in correlations between NTL exposure and temperament. Demographic information, stool samples, and temperament scores were collected from 40 infants. Temperament was evaluated using the Infants Behavior Questionnaire-Revised (IBQ-R). The gut microbiota was analyzed using 16S rRNA sequencing. Cumulative and lagged effects of NTL exposure were calculated based on residential address (NTLpoint) and a concentric 1 km radius buffer zone around the address (NTL1000m), respectively. Mediation models were utilized for assessing the mediating effects of the gut microbiome. The gut microbiome of infants with higher fear scores was characterized by a higher abundance of Akkermansia and Clostridium_sensu_stricto_1 and a lower abundance of Bacteroides. Mediation models indicated Akkermansia played a full mediating role in associations between NTLpoint, NTL1000m and fear in specific time periods. Genus Akkermansia explained 24.46% and 33.50% of associations between fear and cumulative exposure to NTLpoint and NTL1000m, respectively. This study provides evidence for the mediating role of Akkermansia between NTL exposure and fear. However, further experimental is required to elucidate the mechanisms through which the gut microbiome mediates between NTL exposure and temperament in infants.

Role and Mechanism of mir-5189-3p in Deep Vein Thrombosis of Lower Extremities.

BACKGROUND: This study is to investigate the role and mechanism of mir-5189-3p in deep vein thrombosis (DVT) in lower extremity. METHODS: The blood samples were collected from Kazakh patients with DVT in lower extremity and were subjected to microRNA sequencing. Bioinformatics were used to identify mir-5189-3p and its target genes. Dual luciferase reporter assay was used to determine the regulatory effect of mir-5189-3p on JAG1. SD rats were randomly divided into normal control, DVT model, hsa-miR-5189-3p mimics and hsa-miR-5189-3p negative control groups. HE staining was used to observe the pathological changes. TUNEL method was used to observe apoptosis. Western blot was used to detect Bax and Bcl-2 protein expression. Real-time quantitative PCR was used to detect JAG1, Notch1 and Hes1 mRNA. RESULTS: The target of Has-miR-5189-3p was JAG1. Co-transfection of miR-5189-3p mimics and pmirGLO/JAG1 wild-type plasmid induced significantly decreased luciferase activity. In hsa-miR-5189-3p mimics and hsa-miR-5189-3p negative control groups, there were more nucleated cells in the thrombus tissues, and the organization degree obviously increased. Signs of blood flow recanalization were observed. The apoptosis of hsa-miR-5189-3p mimics and hsa-miR-5189-3p negative control groups was lower than that in DVT model group. Furthermore, mir-5189-3p mimics significantly increased the mRNA levels of JAG1, Notch1 and Hes1. Additionally, mir-5189-3p mimics significantly increased Bcl-2 while decreased Bax protein. CONCLUSIONS: mir-5189-3p could inhibit apoptosis and promote thrombus organization in DVT possibly via Notch signaling pathway. Mir-5189-3p can be used as a potential target for DVT treatment.

Outcomes of Selective Strategies for Distal Entry Tears After Thoracic Endovascular Aortic Repair in Type B Aortic Dissection.

BACKGROUND: Distal entry tears have undesirable influence in type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR), including inhibition of aortic remolding and increase of late aortic events. Therefore, distal entry tears should be managed. Nowadays, main strategies for managing distal entry tears included total and selective strategies. However, which strategy is better still remains controversial. The objective of the study is to investigate the outcomes of selective strategy for distal entry tears after TEVAR in TBAD. METHODS: A total of 43 consecutive patients with TBAD with distal entry tears after TEVAR were administered with selective strategy for distal entry tears, including occlusion of the tear in the thoracic aortic segment, thrombosis of the reverse blood flow channel in the false lumen, and selective occlusion of distal entry tears. Mortality, complications, and aortic remolding in early follow-up (12 months after operation) were analyzed. RESULTS: All 43 patients survived during the follow-up period. Operation was performed again for femoral artery reconstruction in 1 patient who had occlusion of the approach vessel during the follow-up period, and the remaining 42 patients had no uncomfortable symptoms and operation-related complications. The maximum diameter of the aorta was 32.03 ± 6.35 mm and 27.36 ± 4.92 mm, respectively, for before and after reintervention, and the difference was significant (t = 5.899, P < 0.001). The unthrombotic range of the false lumen after reintervention was significantly shrunken in all patients, compared with the range before reintervention. CONCLUSIONS: Selective strategy was safe and effective, at least in early follow-up. Its effectiveness should be further verified by more clinical observation results and long-term follow-up results.

Interleukin-2 mediated associations between gut microbiota and acute myeloid leukemia: A population-based mediation Mendelian randomization study.

The relationship between the gut microbiota and acute myeloid leukemia (AML) has been established, but the exact role of interleukin (IL) in mediating this relationship has remained unclear. This study aimed to utilize whether interleukins mediate the relationships between gut microbiota and AML, thereby identifying potential novel targets for future AML treatment. Mendelian randomization (MR) is a method for finding the causality of exposure and outcome. Final instrumental variables were selected based on MR assumptions, and used to judge validity of the results. Our study identified risk and protective factors for AML, and interleukin-related gut microbiota. Finally, mediation MR analyses resulted in Interleukin-2 (IL-2) mediated associations between Clostridiaceae 1, Clostridium sensu stricto 1 and AML, with IL-2 respectively explaining 13.96 % and 12.11 % of the total effect of the aforementioned gut microbiota on AML. Our results successfully identified causal effects between specific gut microbiota, AML, and interleukins, while also elucidating the mediating role of IL-2 in these associations using MR analysis. These findings provide valuable insights into potential therapeutic targets for AML treatment.

Combined impact of Hepatitis B virus and gestational diabetes mellitus on ultrasound-measured fetal growth and adverse perinatal outcomes: A seven-year retrospective study.

AIMS: To investigate the impact of pregnancy with combined hepatitis B virus (HBV) infection and Gestational diabetes mellitus (GDM) on fetal growth and adverse perinatal outcomes. METHODS: All the pregnant women with HBV infection and/or GDM who delivered at Women's Hospital, Zhejiang University between January 2015, and September 2022 were included. A total of 1633 pregnant women were recruited in the final analysis, including 409 women with HBV infection and GDM, 396 with HBV infection only, 430 with GDM only, and 398 without HBV infection and GDM. Linear and logistic regression models were used to study the impact of pregnancy with combined HBV infection and GDM on fetal growth and adverse perinatal outcomes. RESULTS: Pregnancy with combined HBV infection and GDM was associated with increased Z-scores on primary fetal ultrasound parameters and significantly increased the risk of fetal femur length overgrowth (OR: 2.88, 95 % CI: 1.13 âˆ¼ 7.35), placental abruption (OR: 3.64, 95 % CI: 1.18 âˆ¼ 11.22), and macrosomia (OR: 4.19, 95 % CI: 1.66 âˆ¼ 10.56) compared to pregnancy without HBV infection and GDM. CONCLUSIONS: Both maternal HBV infection and GDM are independently associated with adverse perinatal outcomes. Their combination further increases the risk of adverse perinatal outcomes.

Inflammatory cytokines and prenatal depression: Is there a mediating role of maternal gut microbiota?

OBJECTIVE: The mechanism of levels of inflammatory cytokines that affects brain function and mood through gut microbiota has not been fully elucidated. This study aimed to investigate the potential mediating role of gut microbiota between maternal inflammatory cytokines levels and prenatal depression. DESIGN: There were 29 women in the prenatal depression group and 27 women in the control group enrolled in this study. The Edinburgh Postnatal Depression Scale (EPDS) score of 10 was considered the cut-off value for prenatal depression. We collected demographic information, stool and blood samples. The gut microbiota was profiled using V3-V4 gene sequence of 16S rRNA, and the concentration of inflammatory cytokines were analyzed. The mediation model was analyzed by using the model 4 in the process procedure for SPSS. RESULTS: There were significance differences in the concentration of interleukin-1beta (IL-1ß)(Z = -2.383, P = 0.017) and IL-17A (Z = -2.439, P = 0.015) between the prenatal depression group and control group. There was no significant difference in α- diversity and ß-diversity between the two groups. Intestinibacter (OR: 0.012; 95% CI, 0.001-0.195) and Escherichia_Shigella (OR: 0.103; 95% CI, 0.014-0.763) were protective factors for prenatal depression, while Tyzzerella (OR: 17.941; 95% CI, 1.764-182.445) and Unclassified_f_Ruminococcaceae (OR: 22.607; 95% CI, 1.242-411.389) were risk factors. And Intestinibacter play a mediation effect between IL-17A and prenatal depression. CONCLUSION: Maternal gut microbiota is a significant mediator of the relationship between inflammatory cytokines and prenatal depression. Further research is still needed in exploring the mediating mechanisms of gut microbiota between inflammatory cytokines and depression.

Cumulative and lagged effects of varying-sized particulate matter exposure associates with toddlers' gut microbiota.

Particulate matter (PM) is an important component of air pollutants and is associated with various health risks. However, the impact of PM on toddlers' gut microbiota is rarely investigated. This study aimed to assess the cumulative and lagged effects of varying-sized PMs on toddlers' gut microbiota. We collected demographic information, stool samples, and exposure to PM from 36 toddlers aged 2-3 years. The toddlers were divided into warm season group and cooler season group according to the collection time of stool samples. The gut microbiota was processed and analyzed using 16S rRNA V3-V4 gene regions. The concentration of PM was calculated using China High Air Pollutants (CHAP) database. To assess the mixed effects of varying-sized PM, multiple-PM models were utilized. There were significant differences between the community composition, α- and ß-diversity between two groups. In multiple-PM models, there was a significant effect of weight quantile sum (PM1, PM2.5, and PM10) on α-diversity indices. In weight quantile sum models, after adjusting for a priori confounders, we found a negative effect of weight quantile sum on Enterococcus (ß = -0.134, 95% CI -0.263 to -0.006), positive effects of weight quantile sum on unclassified_f__Ruminococcaceae (ß = 0.247, 95% CI 0.102 to 0.393), Ruminococcus_1 (ß = 0.444, 95% CI 0.238 to 0.650), unclassified_f__Lachnospiraceae (ß = 0.278, 95% CI 0.099 to 0.458), and Family_XIII_AD_3011_group (ß = 0.254, 95% CI 0.086 to 0.422) in WSG and CSG. In lagged weight quantile sum models, the correlation between lag time PM levels and the gut microbiota showed seasonal trends, and weights of PM changed with lag periods. This is the first study to highlight that cumulative and lagged effects of PMs synergistically affect the diversities (α- and ß-diversity) and abundance of the gut microbiota in toddlers. Further research is needed to explore the mediating mechanism of varying-sized PMs exposure on the gut microbiota in toddlers.

Expression and role of interleukin-1ß and associated biomarkers in deep vein thrombosis.

Lower extremity deep vein thrombosis (DVT) is a common peripheral vascular disease, in which inflammation plays an important role. The aim of the present study was to investigate the expression and role of inflammatory factors in DVT. A rat model of venous thrombosis of the lower extremities was established through venous ligation surgery. The rats were examined at 2, 8, 24, 48 and 72 h after the induction of inferior venous stenosis and compared with control and sham surgery groups. The serum levels of interleukin-1ß (IL-1ß), tissue factor (TF) and xanthine oxidase (XOD) were measured using ELISAs. The morphology of the DVT tissue was observed by hematoxylin and eosin staining. Circulating endothelial cells (CECs) in peripheral blood were counted by flow cytometry. Reverse transcription-quantitative PCR and western blotting were used to detect mRNA and protein expression, respectively. The serum levels of IL-1ß, TF and XOD exhibited no significant differences between the control and sham surgery groups. However, those in the rat model of DVT presented an upward trend from 2 to 24 h and peaked at 24 h, with a significant difference from the respective levels in the control and sham surgery groups. The histopathological analysis revealed the presence of red and mixed thrombi in the rats 2-48 h following the induction of inferior venous stenosis group with inflammatory cell infiltration in the vascular wall. Thrombus formation was evident after 72 h. While significant difference was observed in the number of CECs in the peripheral blood between the control and sham surgery groups, the number of peripheral blood CECs in the rats with inferior venous stenosis group increased from 8 to 72 h, with significant differences among these groups. The mRNA levels of IL-1ß, TF, XOD and NF-κB in the tissues peaked at 24 h, with significant differences compared with those in the control and sham surgery groups. In addition, the protein expression level of NF-κB increased from 2 to 72 h. In conclusion, these results suggest that the high expression of IL-1ß, TF, XOD and NF-κB may promote thrombus formation.

Polymorphism of IL-1ß rs16944(T/C) Associated with Serum Levels of IL-1ß and Subsequent Stimulation of Extracellular Matrix Degradation Affects Intervertebral Disk Degeneration Susceptibility.

PURPOSE: To investigate the association of polymorphism of IL-1ß rs16944(T/C) with intervertebral disk degeneration (IDD), explore the possible mechanism and evaluate the predictive value of IL-1ß for IDD. PATIENTS AND METHODS: A total of 196 consecutive patients with IDD were recruited, and 196 healthy controls were matched to these patients based on sex and age (±3 years). The polymorphisms of IL-1ß rs16944(T/C), rs1143623(G/C), rs10490571(T/C) and rs2853550(A/G) were determined, and serum IL-1ß, MMP-1, MMP-3, MMP-9 and a disintegrin-like and metalloproteinase with thrombospondin motif-4 (ADAMTS-4) levels were measured. Univariate analysis was performed with Student t-test or one-way ANOVA followed by post hoc and Chi-square test. Variables with two-sided P<0.10 were included in multivariate analysis, which employed a backward stepwise logistic regression model. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value. RESULTS: Multivariate analysis showed that the polymorphism of IL-1ß rs16944(T/C) was independently associated with IDD. The risk for IDD was significantly increased in TT and TC genotype compared with CC genotype, and the OR of TT genotype was higher than that of TC genotype. ANOVA analysis showed that serum concentration of IL-1ß was highest in IL-1ß rs16944 TT genotype, intermediate in TC genotype, and lowest in CC genotype. Similarly, serum concentrations of MMP-3 and ADAMTS-4 demonstrated the same tendency of TT > TC > CC genotype. Serum concentrations of MMP-1 and MMP-9 were higher in TT genotype than in TC and CC genotype. The area under curve (AUC) of IL-1ß levels in predicting IDD was 0.788 (SE: 0.023, P=0.001, 95% CI: 0.742-0.834), and the predictive value was modest with a sensitivity of 77.0% and a specificity of 75%. CONCLUSION: Polymorphism of IL-1ß rs16944(T/C) affected IDD susceptibility through upregulation of serum levels of IL-1ß and subsequent stimulation of ECM degradation. IL-1ß levels could be applied in predicting IDD.

Thrombolysis Combined Therapy Using CuS@SiO2-PEG/uPA Nanoparticles.

Massive hemorrhage caused by the uncontrolled release of thrombolysis drugs is a key issue of thrombolysis therapy in clinical practice. In this study, we report a near-infrared (NIR) light-triggered drug delivery system, i.e., CuS@mSiO2-PEG (CSP) nanoparticles, for the loading of a thrombolytic drug (urokinase plasminogen activators, uPA). CSP nanoparticles with the CuS nanoparticles as photothermal agents and mesoporous SiO2 for the loading of uPA were synthesized using a facile hydrothermal method. The CSP core-shell nanoparticles were demonstrated to possess excellent photothermal performance, exhibiting a photothermal conversion efficiency of up to 52.8%. Due to the mesoporous SiO2 coating, the CSP core-shell nanoparticles exhibited appropriate pore size, high pore volume, and large surface area; thus, they showed great potential to be used as drug carriers. Importantly, the release of uPA from CuS@mSiO2-PEG/uPA (CSPA) carriers can be promoted by the NIR laser irradiation. The drug loading content of uPA for the as-prepared NIR-triggered drug delivery system was calculated to be 8.2%, and the loading efficiency can be determined to be as high as 89.6%. Due to the excellent photothermal effect of CSP nanocarriers, the NIR-triggered drug delivery system can be used for infrared thermal imaging in vivo. The in vivo thrombolysis assessment demonstrated that the NIR-triggered drug delivery system showed excellent thrombolytic ability under the irradiation of an 808 nm laser, showing the combined therapy for thrombolysis. As far as we know, the CSPA core-shell nanoparticles used as NIR-triggered drug delivery systems for thrombolysis have not been reported.

Identification of Novel Long Noncoding RNAs and Their Role in Abdominal Aortic Aneurysm.

OBJECTIVE: Long noncoding RNAs (lncRNAs) have emerged as critical molecular regulators in various diseases. However, the potential regulatory role of lncRNAs in the pathogenesis of abdominal aortic aneurysm (AAA) remains elusive. The aim of this study was to identify crucial lncRNAs associated with human AAA by comparing the lncRNA and mRNA expression profiles of patients with AAA with those of control individuals. MATERIALS AND METHODS: The expression profiles of lncRNAs and mRNAs were analyzed in five dilated aortic samples from AAA patients and three normal aortic samples from control individuals using microarray technology. Functional annotation of the screened lncRNAs based on the differentially expressed genes was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Microarray results revealed 2046 lncRNAs and 1363 mRNAs. Functional enrichment analysis showed that the mRNAs significantly associated with AAA were enriched in the NOD-like receptor (NLR) and nuclear factor kappa-B (NF-κB) signaling pathways and in cell adhesion molecules (CAMs), which are closely associated with pathophysiological changes in AAA. The lncRNAs identified using microarray analysis were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) analysis with 12 versus 11 aortic samples. Finally, three key lncRNAs (ENST00000566954, ENST00000580897, and T181556) were confirmed using strict validation. A coding-noncoding coexpression (CNC) network and a competing endogenous RNA (ceRNA) network were constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs. CONCLUSIONS: Our microarray profiling analysis and validation of significantly expressed lncRNAs between patients with AAA and control group individuals may provide new diagnostic biomarkers for AAA. The underlying regulatory mechanisms of the confirmed lncRNAs in AAA pathogenesis need to be determined using in vitro and in vivo experiments.

Association Between Three SNPs and Thromboangiitis Obliterans in Xinjiang Uyghur Population.

BACKGROUND: Thromboangiitis obliterans (TAO), also called Buerger's disease, is a chronic peripheral vascular occlusive disease. It is an obliterative vasculitis characterized by arterial thrombosis and strongly associated with tobacco exposure. The pathogenesis and etiology of TAO are not well understood, but genetic factors may be important in its development. A case-control study was undertaken to identify genetic factors potentially involved in the pathogenesis of TAO in a Xinjiang Uyghur population of China, where TAO is common. METHODS: We ascertained 177 TAO patients by clinical screening and 86 healthy individuals from the HAPMAP database. The genotypes of single-nucleotide polymorphisms (SNPs) of the participants were identified using the Affymetrix Genome-Wide Human SNP Array 6.0 to perform a genome wide association study (GWAS). The association between the SNPs and incidence of TAO was quantified using race stratification exposure. RESULTS: Through a case-control GWAS study 26 SNPs were significantly associated with incidence of TAO following a Bonferroni correction. However, after genomic control correction for population stratification only three of these SNPS were highly significantly associated with TAO: rs376511 in IL17RC (OR = 24.4, 95% CI:8.68 - 68.62, p < 0.0001), rs7632505 in SEMA5B (OR = 29.47, 95% CI:7.16 - 121.3, p < 0.0001), and rs10178082 (OR = 18.09, 95% CI: 6.56 - 49.92, p < 0.0001) showed a significant risk of TAO in the Uyghur population. CONCLUSIONS: This study shows an association between these 3 SNPs and susceptibility to TAO in the Uyghur population, suggesting that polymorphisms in the IL-17RC and Sema 5B genes may pre-dispose individuals in this population to development of TAO. These findings require replication.

Association between prothrombin gene polymorphisms and hereditary thrombophilia in Xinjiang Kazakhs population.

To assess the association between polymorphisms of prothrombin gene and hereditary thrombophilia in Xinjiang Kazakhs population. Through cross-sectional investigation, permanent Kazakh population of Ili Kazakh Autonomous Prefecture was selected as the study object to measure their antithrombin III (AT-III), protein C, protein S activity and activated C protein resistance value, thus defining the situation of the crowd's hereditary thrombophilia. Sequenom Massarray detection technology was used to conduct a genotype test of the six sites selected by the case and control groups. Haploview software was used to perform linkage disequilibrium analysis of the six sites, and the impact of the interaction between genetic variations and environment on hereditary thrombophilia was researched by the use of sum model. A total of 1005 Kazakh volunteers participated in the test (332 men and 673 women), average age (41.13 ±â€Š11.50) years; the prevalence of hereditary thrombophilia in Xinjiang Kazakh population was 31.0%, and the prevalence of AT-III deficiency, protein C deficiency, protein S deficiency and activated protein C resistance was 16.4, 14.9, 20.6 and 7.8%, respectively. The difference in allele frequency of the hereditary thrombophilia patient group at rs3136447 and rs5896 sites was statistically significant (P = 0.0483 and P = 0.0302, respectively). rs5896 and rs2070852 had high linkage disequilibrium (r = 0.99), and constituted a single-domain block 1. The rs3136447 and the rs5896 polymorphisms located in the region of the prothrombin gene may be associated with hereditary thrombophilia in the Xinjiang Kazakhs population. There is additive interactive effect of rs5896 polymorphism (CT + TT) and smoke on hereditary thrombophilia.