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Medicine Jun 2024Abdominal aortic aneurysm (AAA) is a cardiovascular disease that seriously threatens human health and brings huge economic burden. At present, its pathogenesis remains...
Abdominal aortic aneurysm (AAA) is a cardiovascular disease that seriously threatens human health and brings huge economic burden. At present, its pathogenesis remains unclear and its treatment is limited to surgical treatment. With the deepening and analysis of studies on the mechanism of ferroptosis, a new idea has been provided for the clinical management of AAA patients, including diagnosis, treatment and prevention. Therefore, this paper aims to construct a competitive endogenous RNA (ceRNA) regulatory axis based on ferroptosis to preliminarily explore the pathogenesis and potential therapeutic targets of AAA. We obtained upregulated and downregulated ferroptosis-related DEGs (FRGs) from GSE144431 dataset and 60 known ferroptosis-related genes. Pearson correlation analysis was used to find aldoketone reductase 1C (AKR1C1) in AAA samples. Enrichment analysis of these genes was performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Correlation test between immune cells and AKR1C1 was investigated through single-sample gene set enrichment analysis (ssGSEA). The AKR1C1-miRNA pairs were predicted by the TargetScan database and miRWalk database. Circular RNA (CircRNA)-miRNA pairs were selected by the CircInteractome database. Overlapping miRNA between circRNA-miRNA and AKR1C1-miRNA pairs was visualized by Venn diagram. Finally, the circRNA-miRNA-mRNA axis was constructed by searching for upstream circRNA and downstream mRNA of overlapping miRNA. Only one downregulated AKR1C1 gene was found in GSE144431 and 60 ferroptosis-related genes. Functional Enrichment and Pathway Analysis of AKR1C1-related genes were further explored, and it was observed that they were mainly enriched in "response to oxidative stress," "glutathione biosynthetic process" and "nonribosomal peptide biosynthetic process," "Ferroptosis," "Glutathione metabolism" and "Chemical carcinogenesis-reactive oxygen species." They were also found to be significantly associated with most immune cells, including Activated Dendritic cells, CD56dim Natural killer cells, Gamma Delta T cells, Immature B cells, Plasmacytoid dendritic cell, Type 2 T helper cell, Activated CD4 T cell and Type 1 T helper cell. Has_circ_0005073-miRNA-543 and AKR1C1-miRNA-543 were identified by Online Database analysis. Therefore, we have established the has_circ_0005073/miRNA-543/AKR1C1 axis in AAA. We found AKR1C1 was differentially expressed between normal and AAA groups. Based on AKR1C1, we constructed the has_circ_0005073/miRNA-543/AKR1C1 axis to analyze AAA.
Topics: Humans; Aortic Aneurysm, Abdominal; Ferroptosis; MicroRNAs; 20-Hydroxysteroid Dehydrogenases; RNA, Messenger; RNA, Circular; Down-Regulation
PubMed: 38941402
DOI: 10.1097/MD.0000000000038749 -
Reconciling Coulter Counter and laser diffraction particle size analysis for aquaculture monitoring.Environmental Monitoring and Assessment Jun 2024The disaggregated inorganic grain size (DIGS) of bottom sediment analyzed with a Coulter Counter (CC) has been used to show that the fraction of sediment deposited in...
The disaggregated inorganic grain size (DIGS) of bottom sediment analyzed with a Coulter Counter (CC) has been used to show that the fraction of sediment deposited in flocs (floc fraction) increased in both the near and far field after the introduction of open cage salmon aquaculture, altering benthic habitat and species composition. As a result, DIGS was identified as a potential indicator of regional environmental changes due to aquaculture. Laser diffraction is an attractive alternative to the CC because of its greater efficiency and larger size range. To determine if a laser diffraction instrument, Beckman-Coulter LS 13 320 (LS), could replace the CC within a Canadian national aquaculture monitoring program, the DIGS of 581 samples from five different regions in eastern Canada were analyzed with an LS and a CC. Results show that the LS could not be used to calculate floc fraction. Instead, % sortable silt and the volume % of inorganic particles < 16 µm were evaluated as alternative proxies for fine sediment properties. LS and CC values for these parameters were correlated, but they were significantly different and the relationship between the instruments was dependent on the area sampled. The LS did not capture variations between areas seen in the CC DIGS data. Where the DIGS from the CC found no sorting in the finest size classes, all the LS samples had similar size distributions characterized by smooth modal peaks. The LS and CC both return values that can be used to monitor changes in the deposition of fine-grained sediment, but the LS cannot determine changes in floc deposition and caution is required if comparing different sedimentary environments.
Topics: Aquaculture; Environmental Monitoring; Particle Size; Geologic Sediments; Canada; Animals; Lasers
PubMed: 38940996
DOI: 10.1007/s10661-024-12786-w -
Investigative Ophthalmology & Visual... Jun 2024The purpose of this study was to investigate the functional effects of peripheral refractive errors on mobility performance through a stair negotiation task.
PURPOSE
The purpose of this study was to investigate the functional effects of peripheral refractive errors on mobility performance through a stair negotiation task.
METHODS
Twenty-one young, normal sighted subjects navigated through an obstacle with steps, wearing spectacles that altered only their peripheral refraction. Lenses were used to induce positive defocus (+2 diopters [D] and +4 D), negative defocus (-2 D and -4 D), or astigmatism (+1.75 D and -3.75 D, axis 45 degrees) in the periphery. Feet trajectories were analyzed, and several gait assessment parameters were obtained. Statistical tests were conducted to determine significant performance differences between the lenses. Peripheral refraction in each subject was measured using a scanning Hartmann-Shack wavefront sensor to assess the impact of intrinsic peripheral refraction on the experiment.
RESULTS
Statistically significant differences in performance appeared when peripheral errors were superimposed. Crossing time with respect to plano lenses increased by 6.2%, 7.6%, 19.2%, and 29.6% for the -2 D, +2 D, -4 D, and +4 D lenses, respectively (P < 0.05 in the last 3 cases). Subjects exhibited slower walking speeds, increased step count, and adopted precautionary measures. High-power positive defocus lenses had the biggest impact on performance, and differences were observed in distance to steps between induced positive and negative defocus.
CONCLUSIONS
In this laboratory-based study without an adaptation period, peripheral refractive errors affected stair negotiation, causing cautious behavior in subjects. Performance differences among types of peripheral defocus may result from magnification effects and intrinsic peripheral refraction. These results highlight the importance of understanding the effects of induced peripheral errors by myopia control and intraocular lenses.
Topics: Humans; Male; Female; Adult; Refraction, Ocular; Refractive Errors; Young Adult; Eyeglasses; Visual Acuity; Gait; Walking
PubMed: 38940761
DOI: 10.1167/iovs.65.6.42 -
MSystems Jun 2024Skin ulceration syndrome (SUS) is currently the main disease threatening aquaculture due to its higher mortality rate and infectivity, which is caused by . Our previous...
Skin ulceration syndrome (SUS) is currently the main disease threatening aquaculture due to its higher mortality rate and infectivity, which is caused by . Our previous studies have demonstrated that SUS is accompanied by intestinal microbiota (IM) dysbiosis, alteration of short-chain fatty acids (SCFAs) content and the damage to the intestinal barrier. However, the mediating effect of IM on intestine dysfunction is largely unknown. Herein, we conducted comprehensive intestinal microbiota transplantation (IMT) to explore the link between IM and SUS development. Furthermore, we isolated and identified a strain with an ability to produce acetic acid from both healthy individual and SUS individual with IM from healthy donors. We found that dysbiotic IM and intestinal barrier function in SUS recipients could be restored by IM from healthy donors. The strain could restore IM community and intestinal barrier function. Consistently, acetate supply also restores intestinal homeostasis of SUS-diseased and -infected . Mechanically, acetate was found to specifically bind to its receptor-free fatty acid receptor 2 (FFAR2) to mediate IM structure community and intestinal barrier function. Knockdown of FFAR2 by transfection of specific FFAR2 siRNA could hamper acetate-mediated intestinal homeostasis . Furthermore, we confirmed that acetate/FFAR2 could inhibit -activated NF-κB-MLCK-MLC signaling pathway to restore intestinal epithelium integrity and upregulated the expression of ZO-1 and Occludin. Our findings provide the first evidence that restores pathogen-induced intestinal barrier dysfunction via acetate/FFAR2-NF-κB-MLCK-MLC axis, which provides new insights into the control and prevention of SUS outbreak from an ecological perspective.IMPORTANCESkin ulceration syndrome (SUS) as a main disease in aquaculture has severely restricted the developmental aquaculture industry. Intestinal microbiota (IM) has been studied extensively due to its immunomodulatory properties. Short-chain fatty acids (SCFAs) as an essential signal molecule for microbial regulation of host health also have attracted wide attention. Therefore, it is beneficial to explore the link between IM and SUS for prevention and control of SUS. In the study, the contribution of IM to SUS development has been examined. Additionally, our research further validated the restoration of SCFAs on intestinal barrier dysfunction caused by SUS via isolating SCFAs-producing bacteria. Notably, this restoration might be achieved by inhibition of NF-κB-MLCK-MLC signal pathway, which could be activated by . These findings may have important implications for exploration of the role of IM in SUS occurrence and provide insight into the SUS treatment.
PubMed: 38940521
DOI: 10.1128/msystems.00602-24 -
Gut Microbes 2024Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the...
Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.
Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.
Topics: Animals; Receptors, CXCR6; Chemokine CXCL16; Mice; Fecal Microbiota Transplantation; Humans; Gastrointestinal Microbiome; Liver; Lymphocytes; Mice, Inbred C57BL; Male; Immunity, Innate; Fatty Liver; Interleukin-22; Non-alcoholic Fatty Liver Disease; Interleukins; Female
PubMed: 38940400
DOI: 10.1080/19490976.2024.2372881 -
Animal Models and Experimental Medicine Jun 2024Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant... (Review)
Review
Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant attention due to their close association with host health. As important mediators between the gut microbiota and the host, SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics, activating G protein-coupled receptors, and inhibiting pathogenic microbial infections. This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health, enhancing energy metabolism, mitigating diseases such as cancer, obesity, and diabetes, modulating the gut-brain axis and gut-lung axis, and promoting bone health.
PubMed: 38940192
DOI: 10.1002/ame2.12464 -
Frontiers in Bioscience (Landmark... Jun 2024
Review
Topics: Animals; Humans; Cocaine; Cocaine-Related Disorders; Gastrointestinal Microbiome; Yin-Yang
PubMed: 38940056
DOI: 10.31083/j.fbl2906215 -
Frontiers in Bioscience (Landmark... May 2024Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence.... (Review)
Review
Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Female; Gastrointestinal Microbiome; Adipose Tissue, Brown; Animals; Insulin Resistance; Fecal Microbiota Transplantation; Obesity
PubMed: 38940030
DOI: 10.31083/j.fbl2906208 -
Frontiers in Bioscience (Landmark... May 2024Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant...
BACKGROUND
Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis.
METHODS
The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB).
RESULTS
PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated.
CONCLUSION
PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.
Topics: Humans; Osteosarcoma; RNA, Long Noncoding; Ferroptosis; STAT3 Transcription Factor; Cell Line, Tumor; Bone Neoplasms; Phospholipid Hydroperoxide Glutathione Peroxidase; Cell Proliferation; Reactive Oxygen Species; Signal Transduction; Cell Movement; Disease Progression; Apoptosis; Gene Expression Regulation, Neoplastic
PubMed: 38940027
DOI: 10.31083/j.fbl2906207 -
Sheng Li Xue Bao : [Acta Physiologica... Jun 2024Noise, as an unavoidable stress (pressure) source in the modern life, affects animals in many ways, both behaviorally and physiologically. Behavioral changes may be... (Review)
Review
Noise, as an unavoidable stress (pressure) source in the modern life, affects animals in many ways, both behaviorally and physiologically. Behavioral changes may be driven by changes in hormone secretion in animals. When animals face with noise stress, the neuroendocrine systems, mainly the hypothalamic-pituitary-adrenal (HPA) axis, are activated, which promotes the secretion and release of stress hormones, and then leads to a series of behavioral changes. The behavioral changes can be easily observed, but the changes in physiological indicators such as hormone levels need to be accurately measured. Currently, many studies have measured the variations of stress hormone levels in animals under different noise conditions. Taking glucocorticoid as an example, this paper summarizes the different measurement methods of stress hormones, especially the non-invasive measurement methods, and compares the advantages and shortcomings of them. It provides a variety of measurement choices for the study of related issues, and also helps us to further understand the sources of animal stress, in order to provide a better habitat for animals.
Topics: Animals; Noise; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Stress, Physiological; Glucocorticoids; Stress, Psychological
PubMed: 38939935
DOI: No ID Found