The Interactive Effects of Nontoxic Levels of Microplastics - Textile Microfibers and Tire Wear Particles, on the Acute Toxicity of Bifenthrin in the Estuarine Grass Shrimp, \u3ci\u3e Palaemonetes pugio\u3c/i\u3e

Contemporary pollution issues are primarily focused on Contaminants of Emerging Concern (CECs) which may include Brominated and Fluorinated flame retardants, Pharmaceuticals and Personal Care Products (PPCPs), Contemporary Use Pesticides (CUPs), nanomaterials and microplastics (Muraya et al., 2014). Tire wear particles and textile microfibers are examples of CECs which may gradually increase in the environment and may cause adverse effect on the health of some aquatic species (Marwood et al., 2011; Taylor et al., 2016). Microplastic particles are so small that they can be ingested by many marine species such as filter feeders and small particle feeders including mollusk and crustaceans, which will bioaccumulate within their body and some of the smallest particles may pass into individual cells where they are transparent and may cause harmful effects on a molecular level. Many studies (Gray and Weinstein, 2017; Qiao et al., 2019; Scherer et al., 2018) have observed that bioaccumulation of different sizes, types and shapes of microplastics and nanoplastics may occur. However, there is very little evidence about interaction between microplastics and coexisting contaminants. Therefore, the objective of this study was to evaluate toxicity of textile microfibers and tire wear particles and their influence on toxicity effect of bifenthrin, a contemporary use pyrethroid insecticide, toward estuarine adult grass shrimp, Palaemonetes pugio, a very widely distributed shallow water benthic macroinvertebrates which constitutes around 56% population of pelagic macrofaunal in tidal creeks of the southeastern coast of the United States

Flow-mediated dilatation to relieve puncture-induced radial artery spasm: A pilot study

  Background: Puncture-induced radial artery spasm (RAS) may extend the duration of coronary an­giography (CAG) or cause transradial access failure. Flow-mediated dilatation (FMD), a widely-used noninvasive approach for assessing endothelial function, was reported to remove the entrapped radial sheath after percutaneous coronary intervention. Herein, the efficacy and safety of FMD in treating puncture-induced RAS before transradial CAG was investigated. Methods: Ninety patients with puncture-induced RAS were randomized in a 1:1:1 ratio into three groups: FMD group was immediately treated with blockage of brachial artery blood for 5 min using a sphygmomanometric cuff and then rapid relief; nitroglycerin (NTG) group was administered with 0.5 mg sublingual NTG instantly; and the no-therapy group was treated with a wait-and-watch strategy. The time of radial pulse recovery, and regional and systemic complications were recorded. Results: The rate of radial pulse recovery within 30 min in FMD group was significantly higher than that in no-therapy group (97% vs. 73%, p = 0.026). The median time to return of radial pulse in FMD group and NTG group was significantly shorter than that in no-therapy group (7 [6.5–9] min vs. 15 [12–18] min, 8 [7–9] min vs. 15 [12–18] min, respectively; both p < 0.001). Headache and decreased blood pressure were more prevalent in NTG group than those in FMD and no-therapy groups. Conclusions: FMD is a feasible, noninvasive and nonpharmacological approach to relieve RAS and facilitate radial artery cannulation after an initial failed attempt. (Cardiol J 2018; 25, 1: 1–6

Molecular genetic analysis of three children with CHDFIDD and literature review

Objective To analyze the clinical and genetic characteristics of three children with congenital heart defects， dysmorphic facial features and intellectual developmental disorders（CHDFIDD）. Methods Three children presenting with CHDFIDD were enrolled. Genomic DNA was extracted from peripheral venous blood of the children and their parents. Whole-exome sequencing（WES） was performed using chip-capture high-throughput sequencing technology. Suspected causative mutations were verified by Sanger sequencing and bioinformatic analysis. Using “CDK13 gene” and “CDK13-related diseases” as search terms， literatures of CNKI and Wanfang database were retrieved until February 2024. Using “CDK13”， “CDK13-related disorder” and “CHDFIDD” as search terms， literatures from the establishment of PubMed database untio February 2024 was retrieved， and the relevant literature was reviewed. Results WES revealed heterozygous variants of the CDK13 gene in three children， including c.2572 C>T （p.Leu858Phe）， c.2579 G>A （p.Arg860Gln）， and c.2602C>T （p.Arg868Trp）， which were verified as de novo variants by Sanger sequencing.Combined with the clinical phenotype， all 3 children were diagnosed with CHDFIDD. However， the possibility that one of the affected children’s parents was a germline chimera for the mutation could not be excluded. According to the ACMG guidelines， all three mutation sites were classified as likely pathogenic. A total of 14 studies consisting of 108 cases were retrieved. Among them， c.2572C>T has not been reported. Conclusions The de novo variants of the CDK13 gene may be the genetic cause of developmental delay/intellectual disability in these three children. The findings in the present study expand the spectrum of CDK13 gene mutations， providing reference for the diagnosis of CHDFIDD

Comparison of velopharyngeal morphology of two palatoplasty techniques in patients with hard and soft cleft palate

PurposeThe study aims to compare the velopharyngeal morphology of hard and soft cleft palate (HSCP) patients after Furlow and Sommerlad palatoplasty.Patients and methodsA total of 51 patients (20 cases in Furlow palatoplasty group, 16 cases in Sommerlad palatoplasty group and 15 normal children in the control group) were included in our study. Velopharyngeal function and speech outcomes of patients with HSCP who had either Furlow palatoplasty or Sommerlad palatoplasty for cleft palate repair were evaluated by perceptual speech assessment (PSA), lateral cephalometric radiographs and nasopharyngoscopy. To assess velopharyngeal morphology of patients treated with two techqiques, we analyzed measurements such as velar length, pharyngeal depth, and the Adequate ratio (the ratio of velar length to pharyngeal depth). Furthermore, skeletal landmarks including cranial base, cervical vertebrae, posterior nasal spine which were defined as the pharyngeal triangle were measured. Finally, the position of the point U relative to the pharyngeal triangle were compared.ResultsVelopharyngeal closure (VPC) rate in Furlow palatoplasty group accounted for 90%, while that in Sommerlad palatoplasty group was 81.3%. PSA of the former group was significantly better than that of the latter group (P < 0.05). Velar length, pharyngeal depth and the Adequate ratio (1.37 ± 0.14 vs. 1.41 ± 0.15) were comparable between the Furlow group and control group (P > 0.05), while Sommerlad group had a shorter velar length, deeper pharyngeal depth and a smaller Adequate ratio (1.20 ± 0.18) compared to the above two groups (P < 0.05). Furhermore, the point U of Sommerlad group in the pharyngeal triangle was higher than that of the other two groups.ConclusionsIn the treatment modality of patients with HSCP, both Furlow palatoplasty and Sommerlad palatoplasty seem to be effective. Furlow palatoplasty appears to have velopharyngeal morphology similar to normal control group., while Sommerlad group shows a shorter velar length, deeper pharyngeal depth and a smaller Adequate rati

The Chemokine Receptor CXCR3 Isoform B Drives Breast Cancer Stem Cells

We are seeking to identify molecular targets that are relevant to breast cancer cells with stem-like properties. There is growing evidence that cancer stem cells (CSCs) are supported by inflammatory mediators expressed in the tumor microenvironment. The chemokine receptor CXCR3 binds the interferon-γ-inducible, ELR-negative CXC chemokines CXCL9, CXCL10, and CXCL11 and malignant cells have co-opted this receptor to promote tumor cell migration and invasion. There are 2 major isoforms of CXCR3: CXCR3A and CXCR3B. The latter is generated from alternative splicing and results in a protein with a longer N-terminal domain. CXCR3 isoform A is generally considered to play a major role in tumor metastasis. When the entire tumor cell population is examined, CXCR3 isoform B is usually detected at much lower levels than CXCR3A and for this, and other reasons, was not considered to drive tumor progression. We have shown that CXCR3B is significantly upregulated in the subpopulation of breast CSCs in comparison with the bulk tumor cell population in 3 independent breast cancer cell lines (MDA-MB-231, SUM159, and T47D). Modulation of CXCR3B levels by knock in strategies increases CSC populations identified by aldehyde dehydrogenase activity or CD44+CD24− phenotype as well as tumorsphere-forming capacity. The reverse is seen when CXCR3B is gene-silenced. CXCL11 and CXCL10 directly induce CSC. We also report that novel CXCR3 allosteric modulators BD064 and BD103 prevent the induction of CSCs. BD103 inhibited experimental metastasis. This protective effect is associated with the reversal of CXCR3 ligand-mediated activation of STAT3, ERK1/2, CREB, and NOTCH1 pathways. We propose that CXCR3B, expressed on CSC, should be explored further as a novel therapeutic target

VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer

Background The function of the non-coding portion of the human genome remains one of the most important questions of our time. Its vast complexity is exemplified by the recent identification of an unusual and notable component of the transcriptome - very long intergenic non-coding RNAs, termed vlincRNAs. Results Here we identify 2,147 vlincRNAs covering 10 percent of our genome. We show they are present not only in cancerous cells, but also in primary cells and normal human tissues, and are controlled by canonical promoters. Furthermore, vlincRNA promoters frequently originate from within endogenous retroviral sequences. Strikingly, the number of vlincRNAs expressed from endogenous retroviral promoters strongly correlates with pluripotency or the degree of malignant transformation. These results suggest a previously unknown connection between the pluripotent state and cancer via retroviral repeat-driven expression of vlincRNAs. Finally, we show that vlincRNAs can be syntenically conserved in humans and mouse and their depletion using RNAi can cause apoptosis in cancerous cells. Conclusions These intriguing observations suggest that vlincRNAs could create a framework that combines many existing short ESTs and lincRNAs into a landscape of very long transcripts functioning in the regulation of gene expression in the nucleus. Certain types of vlincRNAs participate at specific stages of normal development and, based on analysis of a limited set of cancerous and primary cell lines, they appear to be co-opted by cancer-associated transcriptional programs. This provides additional understanding of transcriptome regulation during the malignant state, and could lead to additional targets and options for its reversal

Protopanaxadiol and Protopanaxatriol-Type Saponins Ameliorate Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus in High-Fat Diet/Streptozocin-Induced Mice

Ginsenoside is a major active component of ginseng, which exhibits various pharmacological properties such as hepatoprotection, tumor suppression and diabetes resistance. In this study, the anti-diabetic effects of protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins were explored and compared in high-fat diet/streptozocin-induced type 2 diabetes mellitus (T2DM) mice. Our results showed that low or high dose (50 mg/kg bodyweight or 150 mg/kg bodyweight) PPD and PPT significantly reduced fasting blood glucose, improved glucose tolerance and insulin resistance in T2DM mice. PPD and PPT also regulated serum lipid-related markers such as reduced total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol in T2DM mice. In addition, PPD and PPT dramatically ameliorated the inflammatory responses by suppressing the secretion of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin-6 in serum level and gene expression in liver level, and improved the antioxidant capacity by increasing the superoxide dismutase and decreasing malondialdehyde levels in the serum of T2DM mice. Moreover, the anti-diabetic effect of PPD and PPT appeared to be partially mediated by the suppression of hepatic metabolism genes expression such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase, as well as facilitating lipid metabolism genes expression such as microsomal TG transfer protein in the liver tissues of T2DM mice. Taken together, our results indicated that PPD and PPT might potentially act as natural anti-diabetic compounds to be used for preventing and treating the T2DM and its complications in the future

Association between dietary supplement use and mortality in cancer survivors with different body mass index and frailty status: a cohort study

BackgroundThe association between Body Mass Index (BMI), frailty index (FI), and dietary supplement in cancer survivors has been a subject of growing interest. This study investigates the relationship of BMI and FI with mortality in American cancer survivors and explores the impact of dietary supplement usage on different BMI and FI groups.MethodsThree thousand nine hundred and thirty-two cancer patients from the National Health and Nutrition Examination Survey (NHANES) database were included in the analyses. BMI, FI, and supplement usage were obtained through the NHANES structured survey and the 49-item FI tool. Weighted logistic and Cox proportional hazards models, Kaplan–Meier survival analyses, and propensity score matching (PSM) were used to elucidate the relationships between BMI, FI, dietary supplement, and mortality outcomes.ResultsThe study found significant associations between higher BMI and increased frailty (Odds ratio [OR] = 1.04, 95% confidence interval [95% CI], 1.02–1.06). BMI < 25 kg/m2 and FI > 0.2 are associated with an increased mortality rate. Dietary supplement use can reduce all-cause and cancer mortality in cancer patients with BMI < 25 kg/m2 (Hazard ratio [HR] = 0.63, 95% CI, 0.47–0.84; HR = 0.48, 95% CI, 0.29–0.80) or FI ≤ 0.2 (HR = 0.77, 95% CI, 0.60–0.99; HR = 0.59, 95% CI, 0.39–0.89). In cancer patients with BMI < 25 kg/m2 and FI ≤ 0.2, dietary supplement users had lower all-cause and cancer mortality (HR = 0.49, 95% CI, 0.30–0.79; HR = 0.25, 95% CI, 0.10–0.60).ConclusionThe study revealed a negative correlation between BMI and the FI among the cancer patient cohort as well as their complex impact on mortality and highlighted the role of dietary supplement in cancer prognosis, indicating benefits for non-frail patients with BMI < 25 kg/m2