Seliciclib alleviates ulcerative colitis by inhibiting ferroptosis and improving intestinal inflammation.

BACKGROUND: Ulcerative colitis (UC) is a chronic, recurrent, non-specific inflammatory disease, and the pathogenesis of the disease remains unclear. Ferroptosis is a form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which are simultaneously closely related to reactive oxygen species (ROS). Although seliciclib is highly effective against immune inflammation, its mechanism on colitis is unclear. This study demonstrated that seliciclib administration partially inhibited ferroptosis, alleviating symptoms and inflammation in experimental colitis. METHODS: The mouse UC model was induced by 3.0 % dextran sodium sulfate (DSS) for 7 days and treated with seliciclib (10 mg/kg) for 5 days. In the in vitro model, LPS (100 µg/ml) was used for induction, and seliciclib (10 µM) was applied for 2 h. Meanwhile, appropriate histopathology, inflammatory response, oxidative stress, and ferroptosis regulators were measured. RESULTS: This study primarily investigated the role of seliciclib in regulating ferroptosis in UC. Bioinformatics analysis indicated that DUOX2 may serve a role involved in the ferroptosis of UC. The experimental findings demonstrated that seliciclib alleviates symptoms and inflammation in DSS-induced UC mice and partially mitigates the occurrence of ferroptosis both in vivo and in vitro, possibly through the modulation of DUOX2. CONCLUSIONS: Ferroptosis is strongly associated with the development of colitis, and seliciclib plays an essential role in ferroptosis and inflammation in UC. The suppression of ferroptosis in the intestinal epithelium could be therapeutic approach for ulcerative colitis.

Roxadustat on Renal Anemia with Macroinflammation: A Retrospective Cohort Study.

Introduction: Roxadustat, the first-in-class drug for the treatment of renal anemia, has demonstrated efficacy in renal anemia with microinflammation. Additional data are needed regarding the efficacy of roxadustat on renal anemia with systemic macroinflammation. Methods: Three cohorts of renal anemia based on the basic level of high-sensitivity CRP were included. Patients with hsCRP ≤2 mg/L were selected as non-inflammation (NI) group; 2< hsCRP ≤10 mg/L as microinflammation (MI) group; hsCRP≥10 mg/L as macroinflammation (MA) group. Patients received oral roxadustat three times per week for 52 weeks. The primary end point was the hemoglobin level over weeks 12-52. The second end point was the cumulative proportion of patients achieving hemoglobin response by the end of week 12. Results: A total of 107 patients with chronic kidney diseases (CKDs) were enrolled. Overall, the baseline hemoglobin level of patients was 79.99 ± 11.20 g/L. Roxadustat could significantly increase the hemoglobin level in all of the three groups and did not show any significant difference (p > 0.05, respectively). Meanwhile, compared with that of the NI group, there was no significant difference in hemoglobin response rate in the MA group both at week 12 (p = 0.06; 95% confidence interval [CI], 0.9531-13.75) and week 52 (p = 0.37; 95% CI, 0.5080-7.937). Moreover, the hemoglobin response was independent of baseline hsCRP level (p = 0.72, 95% CI, -0.1139 to 0.0794). More importantly, roxadustat significantly reduced ferritin and serum iron levels and increased total iron-binding capacity in the three groups, which showed no significant differences among the three groups (p > 0.05, respectively). Conclusion: Roxadustat significantly improves anemia in CKD patients with systemic macroinflammation.

LncRNA AFAP1-AS1 mediates breast cancer cell proliferation and migration through the miR-21/PTEN axis.

LncRNAs play various effects, mostly by sponging with miRNAs. Based on public databases integrating bioinformatics analyses and further validation in breast cancer (BC) tissue and cell lines, the effect of lncRNA AFAP1-AS1 on breast cancer cell proliferation and migration was verified. It might work via the miR-21/PTEN axis. The expression of AFAP1-AS1, which was significantly upregulated in BC tissues and cell lines, was correlated with old age and lymph node metastasis of patients with BC. Knockdown of AFAP1-AS1 inhibited the proliferation and migration of BC cells in vitro and in vivo. And downregulated miR-21 expression and upregulated PTEN expression additionally. Mechanistically, the knockdown of lncRNA AFAP1-AS1 upregulated PTEN expression and consequently attenuated miR-21-mediated enhanced BC cell proliferation and migration. LncRNA AFAP1-AS1 is a potential prognostic biomarker for BC patients.

Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation.

BACKGROUND: Radiation esophagitis (RE) is one of the most common clinical symptoms of regi-onal lymph node radiotherapy for breast cancer. However, there are fewer studies focusing on RE caused by hypofractionated radiotherapy (HFRT). AIM: To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes. METHODS: Between January and December 2022, we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F. RESULTS: Of the 64 patients in this study, 24 (37.5%) did not develop RE, 29 (45.3%) developed grade 1 RE (G1RE), 11 (17.2%) developed grade 2 RE (G2RE), and none developed grade 3 RE or higher. Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose, mean dose, relative volume 20-40, and absolute volume (AV) 20-40. Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE (P < 0.001). The optimal threshold for AV30 was 2.39 mL [area under the curve (AUC): 0.996; sensitivity: 90.9%; specificity: 91.1%]. The optimal threshold for AV35 was 0.71 mL (AUC: 0.932; sensitivity: 90.9%; specificity: 83.9%). CONCLUSION: AV30 and AV35 were significantly associated with G2RE. The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL, respectively.

Disulfidptosis­related lncRNA prognosis model to predict survival therapeutic response prediction in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, and disulfidptosis is a newly discovered mechanism of programmed cell death. However, the effects of disulfidptosis-related lncRNAs (DR-lncRNAs) in LUAD have yet to be fully elucidated. The aim of the present study was to identify and validate a novel lncRNA-based prognostic marker that was associated with disulfidptosis. RNA-sequencing and associated clinical data were obtained from The Cancer Genome Atlas database. Univariate Cox regression and lasso algorithm analyses were used to identify DR-lncRNAs and to establish a prognostic model. Kaplan-Meier curves, receiver operating characteristic curves, principal component analysis, Cox regression, nomograms and calibration curves were used to assess the reliability of the prognostic model. Functional enrichment analysis, immune infiltration analysis, somatic mutation analysis, tumor microenvironment and drug predictions were applied to the risk model. Reverse transcription-quantitative PCR was subsequently performed to validate the mRNA expression levels of the lncRNAs in normal cells and tumor cells. These analyses enabled a DR-lncRNA prognosis signature to be constructed, consisting of nine lncRNAs; U91328.1, LINC00426, MIR1915HG, TMPO-AS1, TDRKH-AS1, AL157895.1, AL512363.1, AC010615.2 and GCC2-AS1. This risk model could serve as an independent prognostic tool for patients with LUAD. Numerous immune evaluation algorithms indicated that the low-risk group may exhibit a more robust and active immune response against the tumor. Moreover, the tumor immune dysfunction exclusion algorithm suggested that immunotherapy would be more effective in patients in the low-risk group. The drug-sensitivity results showed that patients in the high-risk group were more sensitive to treatment with crizotinib, erlotinib or savolitinib. Finally, the expression levels of AL157895.1 were found to be lower in A549. In summary, a novel DR-lncRNA signature was constructed, which provided a new index to predict the efficacy of therapeutic interventions and the prognosis of patients with LUAD.

Erratum: Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury: Erratum.

[This corrects the article DOI: 10.7150/thno.54550.].

Superoxide dismutase 1-modified dental pulp stem cells alleviate high-altitude pulmonary edema by inhibiting oxidative stress through the Nrf2/HO-1 pathway.

High-altitude pulmonary edema (HAPE) is a deadly form of altitude sickness, and there is no effective treatment for HAPE. Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell isolated from dental pulp tissues and possess various functions, such as anti-inflammatory and anti-oxidative stress. DPSCs have been used to treat a variety of diseases, but there are no studies on treating HAPE. In this study, Sprague-Dawley rats were exposed to acute low-pressure hypoxia to establish the HAPE model, and SOD1-modified DPSCs (DPSCsHiSOD1) were administered through the tail vein. Pulmonary arterial pressure, lung water content (LWC), total lung protein content of bronchoalveolar lavage fluid (BALF) and lung homogenates, oxidative stress, and inflammatory indicators were detected to evaluate the effects of DPSCsHiSOD1 on HAPE. Rat type II alveolar epithelial cells (RLE-6TN) were used to investigate the effects and mechanism of DPSCsHiSOD1 on hypoxia injury. We found that DPSCs could treat HAPE, and the effect was better than that of dexamethasone treatment. SOD1 modification could enhance the function of DPSCs in improving the structure of lung tissue, decreasing pulmonary arterial pressure and LWC, and reducing the total lung protein content of BALF and lung homogenates, through anti-oxidative stress and anti-inflammatory effects. Furthermore, we found that DPSCsHiSOD1 could protect RLE-6TN from hypoxic injury by reducing the accumulation of reactive oxygen species (ROS) and activating the Nrf2/HO-1 pathway. Our findings confirm that SOD1 modification could enhance the anti-oxidative stress ability of DPSCs through the Nrf2/HO-1 signalling pathway. DPSCs, especially DPSCsHiSOD1, could be a potential treatment for HAPE. Schematic diagram of the antioxidant stress mechanism of DPSCs in the treatment of high-altitude pulmonary edema. DPSCs can alleviate oxidative stress by releasing superoxide dismutase 1, thereby reducing ROS production and activating the Nrf2/HO-1 signalling pathway to ameliorate lung cell injury in HAPE.

Development and validation of a nomogram for assessing survival in acute exacerbation of chronic obstructive pulmonary disease patients.

BACKGROUND: Early prediction of survival of hospitalized acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients is vital. We aimed to establish a nomogram to predict the survival probability of AECOPD patients. METHODS: Retrospectively collected data of 4601 patients hospitalized for AECOPD. These patients were randomly divided into a training and a validation cohort at a 6:4 ratio. In the training cohort, LASSO-Cox regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of AECOPD patients. A model was established based on 3 variables and visualized by nomogram. The performance of the model was assesed by AUC, C-index, calibration curve, decision curve analysis in both cohorts. RESULTS: Coexisting arrhythmia, invasive mechanical ventilation (IMV) usage and lower serum albumin values were found to be significantly associated with lower survival probability of AECOPD patients, and these 3 predictors were further used to establish a prediction nomogram. The C-indexes of the nomogram were 0.816 in the training cohort and 0.814 in the validation cohort. The AUC in the training cohort was 0.825 for 7-day, 0.807 for 14-day and 0.825 for 21-day survival probability, in the validation cohort this were 0.796 for 7-day, 0.831 for 14-day and 0.841 for 21-day. The calibration of the nomogram showed a good goodness-of-fit and decision curve analysis showed the net clinical benefits achievable at different risk thresholds were excellent. CONCLUSION: We established a nomogram based on 3 variables for predicting the survival probability of AECOPD patients. The nomogram showed good performance and was clinically useful.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice.

BACKGROUND: Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflammation-related diseases. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases. AIM: To modify DPSCs with HGF (DPSC-HGF) and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout (ApoE-/-) mouse model and an in vitro cellular model. METHODS: ApoE-/- mice were fed with a high-fat diet (HFD) for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs (DPSC-Null) through tail vein at weeks 4, 7, and 11, respectively, and the therapeutic efficacy and mechanisms were analyzed by histopathology, flow cytometry, lipid and glucose measurements, real-time reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay at the different time points of the experiment. An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells (HAOECs), and indirect co-cultured with supernatant of DPSC-Null (DPSC-Null-CM) or DPSC-HGF-CM, and the effect and mechanisms were analyzed by flow cytometry, RT-PCR and western blot. Nuclear factor-κB (NF-κB) activators and inhibitors were also used to validate the related signaling pathways. RESULTS: DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors, and the percentage of macrophages in the aorta, and DPSC-HGF treatment had more pronounced effects. DPSCs treatment had no effect on serum lipoprotein levels. The FACS results showed that DPSCs treatment reduced the percentages of monocytes, neutrophils, and M1 macrophages in the peripheral blood and spleen. DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-α stimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway. CONCLUSION: This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/- mice on a HFD, and could be of greater value in stem cell-based treatments for AS.

HIF-1α and adaptor protein LIM and senescent cell antigen-like domains protein 1 axis promotes tubulointerstitial fibrosis by interacting with vimentin in angiotensin II-induced hypertension.

BACKGROUND AND PURPOSE: Activation of the renin-angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen-like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)-induced hypertension and tubulointerstitial fibrosis was investigated. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) renal tubular-specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II-induced renal interstitial fibrosis. In vitro, HIF-1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. KEY RESULTS: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II-induced hypertension model. Tubular-specific knockdown of LIMS1 ameliorated Ang II-induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF-1α in tubular cells and that tubular HIF-1α knockout ameliorates LIMS1-mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II-induced tubulointerstitial fibrosis by interacting with vimentin. CONCLUSION AND IMPLICATIONS: We conclude that HIF-1α transcriptionally regulated LIMS1 plays a central role in Ang II-induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II-induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD.

Diagnostic performance of the gallbladder reporting and data system combined with color doppler flow imaging for gallbladder cancer in the Asian population.

Purpose: Evaluating the performance of the Gallbladder Reporting and Data System (GB-RADS) combined with Color Doppler Flow Imaging (CDFI) for the diagnosis of gallbladder wall thickening disease in an Asian population. Methods: In this study, the lesions were classified and the actual incidence rate of malignant tumors was calculated for each GB-RADS category, following the guidelines provided by GB-RADS. To evaluate the diagnostic performance of GB-RADS and GB-RADS combined with CDFI, we plotted Receiver Operator Characteristic (ROC) curves. The sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (AC) were also calculated. Inter-observer agreement (IRA) between the two observers was assessed using Kappa values. Results: The incidence of malignancy risk for GB-RADS 2, 3, 4, and 5 was 9%, 12.5%, 72.2%, and 100%. The AUC for GB-RADS was 0.855 (95% CI: 0.800-0.900), with a sensitivity of 82.5%, a specificity of 84.6%, and an accuracy of 83.8%. The AUC of GB-RADS combined with CDFI was 0.965 (95% CI: 0.930-0.985), with a sensitivity of 96.2%, a specificity of 94.6%, and an accuracy of 95.2%. The AUC, sensitivity, specificity, and accuracy of GB-RADS combined with CDFI for diagnosing gallbladder malignancy were higher than those of GB-RADS alone, and the differences were statistically significant (all P < 0.05). The IRA was excellent between the two observers (Kappa = 0.870). Conclusions: GB-RADS combined with CDFI demonstrated excellent diagnostic accuracy when it comes to distinguishing various diseases that caused gallbladder wall thickening in the Asian population, which has good clinical value and can improve the detection rate of malignant tumors in patients with gallbladder wall thickening.

Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study.

BACKGROUND: Through research on the gut microbiota (GM), increasing evidence has indicated that the GM is associated with esophageal cancer (ESCA). However, the specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate the causal relationship between the GM and ESCA, including its subtypes. METHODS: We collected information on 211 GMs and acquired data on ESCA and its subtypes through genome-wide association studies (GWASs). The causal relationship was primarily assessed using the inverse variance weighted (IVW) method. Additionally, we applied the weighted median estimator (WME) method, MR-Egger method, weighted mode, and simple mode to provide further assistance. Subsequent to these analyses, sensitivity analysis was conducted using the MR-Egger intercept test, MR-PRESSO global test, and leave-one-out method. RESULT: Following our assessment using five methods and sensitivity analysis, we identified seven GMs with potential causal relationships with ESCA and its subtypes. At the genus level, Veillonella and Coprobacter were positively correlated with ESCA, whereas Prevotella9, Eubacterium oxidoreducens group, and Turicibacter were negatively correlated with ESCA. In the case of esophageal adenocarcinoma (EAC), Flavonifractor exhibited a positive correlation, while Actinomyces exhibited a negative correlation. CONCLUSION: Our study revealed the potential causal relationship between GM and ESCA and its subtypes, offering novel insights for the advancement of ESCA diagnosis and treatment.

Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood. Here, we found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/- mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis. Overall, these data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.

Revealing a Novel Methylated Integrin Alpha-8 Related to Extracellular Matrix and Anoikis Resistance Using Proteomic Analysis in the Immune Microenvironment of Lung Adenocarcinoma.

Genomic epigenetics of extracellular matrix (ECM) play an important role in lung adenocarcinoma (LUAD). Our study identified a signature of potential prognostic genes associated with ECM and constructed immune risk-related prognosis model in LUAD. We downloaded mRNAs transcriptome data, miRNAs expression data, and clinical patient information for LUAD based on The Cancer Genome Atlas. "Limma, clusterProfiler, ggplot2" R packages and GSEA were used to analyze meaningful genes and explore potential biological function. A competing endogenous RNA network was constructed to reveal the mechanism of ECM-related genes. Combined with clinical LUAD patients' characteristics, univariate and multivariate Cox regression analyses were used to build prognostic immune risk model. Next, we calculated AUC value of ROC curve, and explored survival probability of different risk groups. A total of 2966 mRNAs were differently expressed in LUAD samples and normal samples. Function enrichment analyses proved mRNAs were associated with many tumor pathways, such as cell adhesion, vascular smooth muscle contraction, and cell cycle. There were 18 mRNAs related to ECM receptor signaling pathway, and 7 mRNAs expressions were correlated with EGFR expression, but only 5mRNAs were associated with the long-term prognosis. Based on Integrin alpha-8 (ITGA8) molecule, we identified potential 3 miRNAs from several databases. The promoter of ITGA8 was higher-methylated and lower-expressed in LUAD. And lower-expressed group has poor prognosis for patients. 66 immunomodulators related to ITGA8 were performed to construct immune correlation prediction model (p < 0.05). Comprehensive analyses of ITGA8 revealed it combined focal adhesion kinase to activate PI3K/AKT signaling pathway to influence the occurrence and development of LUAD. A novel immune prognostic model about ITGA8 was constructed and verified in LUAD patients. Combined with non-coding genes and genomic epigenetics, identification of potential biomarkers provided new light on therapeutic strategy for clinical patients.

The association between chronic obstructive pulmonary disease and autoimmune diseases: a bidirectional Mendelian randomization study.

Objective: Observational studies have reported that chronic obstructive pulmonary disease (COPD) is often accompanied by autoimmune diseases, but the causal relationships between them remain uncertain. In this Mendelian study, we aimed to investigate the potential causal relationship between COPD and four common autoimmune diseases. Methods: We conducted an analysis of summary data on COPD and autoimmune disease using publicly available genome-wide association studies (GWAS) summary data. We initially employed the inverse- variance weighted method as the primary approach to establish the causal impact of COPD on autoimmune diseases in the sample and conducted additional sensitivity analyses to examine the robustness of the results. Subsequently, we performed reverse Mendelian randomization (MR) analyses for the four autoimmune diseases. Finally, the potential for bidirectional causal relationships was assessed. Results: Our MR analysis revealed no significant causal relationship between COPD and any of the studied autoimmune diseases. However, reverse MR results indicated a significant association between rheumatoid arthritis (RA), osteoarthritis (OA) and the risk of developing COPD, with respective odds ratios (OR) of 377.313 (95% CI, 6.625-21487.932, P = 0.004) for RA and 11.097 (95% CI, 1.583-77.796, P = 0.015) for OA. Sensitivity analyses confirmed the robustness of the results. Conclusion: Our findings support a potential causal relationship between autoimmune diseases and COPD, highlighting the importance of considering comorbidities in clinical management of COPD.

Associations between the platelet/high-density lipoprotein cholesterol ratio and likelihood of nephrolithiasis: a cross-sectional analysis in United States adults.

Aims: The primary objective of this study was to investigate the relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR) and the prevalence of nephrolithiasis within the adult population of the United States. Methods: The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2018. The analysis included a non-pregnant population aged 20 years or older, providing proper PHR index and nephrolithiasis data. The research utilized subgroup analyses and weighted univariate and multivariable logistic regression to evaluate the independent association between the PHR and the susceptibility to nephrolithiasis. Results: The study comprised 30,899 participants with an average PHR value of 19.30 ± 0.11. The overall prevalence rate of nephrolithiasis was estimated at 9.98% with an increase in the higher PHR tertiles (T1, 8.49%; T2, 10.11%; T3, 11.38%, P < 0.0001). An elevated PHR level was closely linked with a higher susceptibility to nephrolithiasis. Compared with patients in T1, and after adjusting for potential confounders in model 2, the corresponding odds ratio for nephrolithiasis in T3 was 1.48 (95% CI: 1.06 to 2.08), with a P-value = 0.02. The results of the interaction tests revealed a significant impact of chronic kidney disease on the relationship between PHR and nephrolithiasis. Furthermore, the restricted cubic spline analyses exhibited a positive, non-linear correlation between PHR and the risk of nephrolithiasis. Conclusion: A convenient biomarker, the PHR, was independently associated with nephrolithiasis and could be a novel biomarker in predicting occurrence in clinical decision.

Tetrabromobisphenol A exerts thyroid disrupting effects but has little overt impact on postnatal brain development and neurobehaviors in mice.

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant. There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals, but different results were also reported, along with inconsistent reports regarding its neurotoxicity. Here, we investigated thyroid disrupting effects and neurotoxicity of TBBPA (5, 50, 500 µg/(kg·day)) to male mice following maternal and direct exposure through drinking water, with the anti-thyroid drug propylthiouracil (PTU) as the positive control. On postnatal day (PND) 15, we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups. The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum. During puberty and adulthood, the thyroid morphological alterations became more pronounced in the TBBPA-treated animals, accompanied by decreased serum thyroid hormone levels. Furthermore, the 50 and 500 µg/(kg·day) TBBPA groups showed a significant decrease in the serum level of serotonin, a neurotransmitter associated with anxiety behaviors. Correspondingly, the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35, but this neurobehavioral alteration disappeared on PND 56. Moreover, no changes in neurobehavioral parameters tested were found in TBBPA-treated animals at puberty and adulthood. Altogether, all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice, suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.

Corrigendum: Associations between omega-3 fatty acids and insulin resistance and body composition in women with polycystic ovary syndrome.

[This corrects the article DOI: 10.3389/fnut.2022.1016943.].