The association between endocrine disrupting chemicals and nonalcoholic fatty liver disease: A systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. Epidemiological studies have reported that exposure of the population to environmental endocrine-disrupting chemicals (EDCs) is associated with NAFLD. However, EDCs are of different types, and there are inconsistencies in the relevant evidence and descriptions, which have not been systematically summarized so far. Therefore, this study aimed to determine the association between population exposure to EDCs and NAFLD. Three databases, including PubMed, Web of science, and Embase were searched, and 27 articles were included in this study. Methodological quality, heterogeneity, and publication bias of the included studies were assessed using the Newcastle-Ottawa scale, I2 statistics, Begg's test, and Egger's test. The estimated effect sizes of the included studies were pooled and evaluated using the random-effects model (I2 > 50 %) and the fixed-effects model ( I2 < 50 %). The pooled-estimate effect sizes showed that population exposure to Phthalates (PAEs) (OR = 1.18, 95 % CI:1.03-1.34), cadmium (Cd) (OR = 1.37, 95 % CI:1.09-1.72), and bisphenol A (OR = 1.43, 95 % CI:1.24-1.65) were positively correlated with the risk of NAFLD. Exposure to mercury (OR =1.46, 95 % CI:1.17-1.84) and Cd increased the risk of "elevated alanine aminotransferase". On the contrary, no significant association was identified between perfluoroalkyl substances (OR =0.99, 95 % CI:0.93-1.06) and NAFLD. However, female exposure to perfluorooctanoic acid (OR =1.82, 95 % CI:1.01-3.26) led to a higher risk of NAFLD than male exposure. In conclusion, this study revealed that EDCs were risk factors for NAFLD. Nonetheless, the sensitivity analysis results of some of the meta-analyses were not stable and demonstrated high heterogeneity. The evidence for these associations is limited, and more large-scale population-based studies are required to confirm these findings.

M6A methylation-regulated autophagy may be a new therapeutic target for intervertebral disc degeneration.

Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy-related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy-related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration.

Myocardial fibrosis induced by nonylphenol and its regulatory effect on the TGF-ß1/LIMK1 signaling pathway.

OBJECTIVE: We here explored whether perinatal nonylphenol (NP) exposure causes myocardial fibrosis (MF) during adulthood in offspring rats and determined the role of the TGF-ß1/LIMK1 signaling pathway in NP-induced fibrosis in cardiac fibroblasts (CFs). METHODS AND RESULTS: Histopathology revealed increased collagen deposition and altered fiber arrangement in the NP and isoproterenol hydrochloride (ISO) groups compared with the blank group. Systolic and diastolic functions were impaired. Western blotting and qRT-PCR demonstrated that the expression of central myofibrosis-related proteins (collagens Ι and ΙΙΙ, MMP2, MMP9, TGF-ß1, α-SMA, IL-1ß, and TGF-ß1) and genes (Collagen Ι, Collagen ΙΙΙ, TGF-ß1, and α-SMA mRNA) was upregulated in the NP and ISO groups compared with the blank group. The mRNA-seq analysis indicated differential expression of TGF-ß1 signaling pathway-associated genes and proteins. Fibrosis-related protein and gene expression increased in the CFs stimulated with the recombinant human TGF-ß1 and NP, which was consistent with the results of animal experiments. According to the immunofluorescence analysis and western blotting, NP exposure activated the TGF-ß1/LIMK1 signaling pathway whose action mechanism in NP-induced CFs was further validated using the LIMK1 inhibitor (BMS-5). The inhibitor modulated the TGF-ß1/LIMK1 signaling pathway and suppressed the NP-induced increase in fibrosis-related protein expression in the CFs. Thus, the aforementioned pathway is involved in NP-induced fibrosis. CONCLUSION: We here provide the first evidence that perinatal NP exposure causes myocardial fibrosis in growing male rat pups and reveal the molecular mechanism and functional role of the TGF-ß1/LIMK1 signaling pathway in this process.

Thrombocytopenia and In-hospital outcomes in patients with acute ischemic stroke undergoing intravenous thrombolysis: Findings from a nationwide registry study in China.

BACKGROUND AND OBJECTIVE: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis. METHODS: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 109/L), mild thrombocytopenia (100 ≤ PC < 150 × 109/L), normal PC (150 ≤ PC ≤ 450 × 109/L), and thrombocythemia (PC > 450 × 109/L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes. RESULTS: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 109/L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02). CONCLUSIONS: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 109/L, especially PC < 100 × 109/L. It indicated that PC < 100 × 109/L is a reasonable contraindication to thrombolysis.

Tert-butyl hydroperoxide induces ferroptosis of bone mesenchymal stem cells by repressing the prominin2/BACH1/ROS axis.

Ferroptosis has been proven critical for survival following bone marrow mesenchymal stem cells (BMSCs) explantation. Suppression of ferroptosis in BMSCs will be a valid tactic to elevate the therapeutic potential of engrafted BMSCs. Prominin2 is a pentaspanin protein involved in mediating iron efflux and thus modulates resistance to ferroptosis, but its role in tert-butyl hydroperoxide (TBHP)-induced BMSCs ferroptosis remains elusive. We examined the biological effect of prominin2 in vitro and in vivo by using cell proliferation assay, iron assay, reactive oxygen species (ROS) examination, malondialdehyde assay, glutathione (GSH) examination, Western blot, quantitative reverse transcription-PCR, immunofluorescence staining assay, gene expression inhibition and activation, co-immunoprecipitation (CO-IP) assay, radiographic analysis, and histopathological analysis. Our study demonstrated that prominin2 activity was impaired in TBHP-induced BMSCs ferroptosis. We found that PROM2 (encoding the protein prominin2) activation delayed the onset of ferroptosis and PROM2 knockdown deteriorated the course of ferroptosis. CO-IP, Western blot, and immunofluorescence demonstrated that prominin2 exerts antiferroptosis effects by inhibiting BTB and CNC homology 1 (BACH1) that promotes ROS generation, and thus exerts potent antioxidant effects in oxidative stress (OS)-induced BMSCs ferroptosis, including elevating BMSCs' survival rate and enhancing GSH contents. BMSCs with PROM2 overexpression also partially delayed the progression of intervertebral disk degeneration in vivo, as illustrated by less loss of disk height and lower histological scores. Our findings revealed a mechanism that the prominin2/BACH1/ROS axis participates in BMSCs ferroptosis and the strengthening of this axis is promising to maintain BMSCs' survival after explantation.NEW & NOTEWORTHY We found that prominin2 might be a potential biomarker and is expected to be utilized to augment engrafted bone marrow mesenchymal stem cells (BMSCs) survival rate. The prominin2/BTB and CNC homology 1 (BACH1)/reactive oxygen species (ROS) axis, which participates in the regulation of BMSCs ferroptosis induced by tert-butyl hydroperoxide (TBHP), is uncovered in our study. The therapeutic targeting of the prominin2/BACH1/ROS axis components is promising to elevate the survival of transplanted BMSCs in clinical practice.

Mitochondria-related lncRNAs: predicting prognosis, tumor microenvironment and treatment response in lung adenocarcinoma.

Lung cancer is the most common type of malignant tumor that affects people in China and even across the globe, as it exhibits the highest rates of morbidity and mortality. Lung adenocarcinoma (LUAD) is a type of lung cancer with a very high incidence. The purpose of this study was to identify potential biomarkers that could be used to forecast the prognosis and improve the existing therapy options for treating LUAD. Clinical and RNA sequencing data of LUAD patients were retrieved from the TCGA database, while the mitochondria-associated gene sets were acquired from the MITOMAP database. Thereafter, Pearson correlation analysis was carried out to screen mitochondria-associated lncRNAs. Furthermore, univariate Cox and Lasso regression analyses were used for the initial screening of the target lncRNAs for prognostic lncRNAs before they could be incorporated into a multivariate Cox Hazard ratio model. Then, the clinical data, concordance index, Kaplan-Meier (K-M) curves, and the clinically-relevant subjects that were approved by the Characteristic Curves (ROC) were employed for assessing the model's predictive value. Additionally, the differences in immune-related functions and biological pathway enrichment between high- and low-risk LUAD groups were examined. Nomograms were developed to anticipate the OS rates of the patients within 1-, 3-, and 5 years, and the differences in drug sensitivity and immunological checkpoints were compared. In this study, 2175 mitochondria-associated lncRNAs were screened. Univariate, multivariate, and Lasso Cox regression analyses were carried out to select 13 lncRNAs with an independent prognostic significance, and a prognostic model was developed. The OS analysis of the established prognostic prediction model revealed significant variations between the high- and low-risk patients. The AUC-ROC values after 1, 3, and 5 years were seen to be 0.746, 0.692, and 0.726, respectively. The results suggested that the prognostic model riskscore could be used as an independent prognostic factor that differed from the other clinical characteristics. After analyzing the findings of the study, it was noted that both the risk groups showed significant differences in their immune functioning, immunological checkpoint genes, and drug sensitivity. The prognosis of patients with LUAD could be accurately and independently predicted using a risk prediction model that included 13 mitochondria-associated lncRNAs.

Mechanistic Exploitations of the Asymmetric α-Allylation of an α-CF3 Amide Enabled by Cu/Pd Synergistic Dual Catalysis.

DFT computational investigations were carried out to explore the mechanism of enantioselective Cu/Pd-catalyzed allylation of an α-CF3 amide. A kinetically favored chiral Cu(I)-enolate species undertakes facile allylation with racemic π-allyl-Pd(II) species to stereoconvergently deliver a stereocenter. Computational models and distortion/interaction analyses unveil versatile modes of stereoinduction wherein the reactive site of (R,Rp)-Walphos/copper(I)-enolate cis to the -PPh2 moiety has more space for the nucleophilic reaction, and can face-selectively capture π-allyl-palladium(II) intermediates using sterically affected distortions.

A nomogram for accurately predicting the surgical site infection following transforaminal lumbar interbody fusion in type 2 diabetes patients, based on glycemic variability.

Surgical site infection (SSI) is a common and serious complication of transforaminal lumbar interbody fusion (TLIF), and the occurrence of SSI usually leads to prolonged hospitalisation, increased medical costs, poor prognosis, and even death. The objectives of this study were to compare the incidence of SSI in patients with type 2 diabetes, investigate the correlation between perioperative glycemic variability and postoperative SSI, and develop a nomogram model to predict the risk of SSI. This study retrospectively analysed 339 patients with type 2 diabetes who underwent TLIF in the spinal surgery department of the Affiliated Zhongda Hospital of Southeast University from January 2018 to September 2021. The medical records of all patients were collected, and postoperative infection cases were determined according to the diagnostic criteria of surgical site infection. The risk factors for postoperative SSI were analysed by univariate and multivariate logistic regression. And Nomogram prediction model was established and validated. The nomogram incorporated seven independent predictors. Preoperative FPG-CV was the most important independent risk predictor of SSI, followed by preoperative MFBG, duration of drain placement, postoperative FPG-CV, preoperative blood glucose control scheme, duration of diabetes >5 years, and the number of fused vertebrae ≥2. The nomogram showed good diagnostic accuracy for the SS of both the training cohort and the validation cohort (AUC = 0.915 and AUC = 0.890). The calibration curves for the two cohorts both showed optimal agreement between nomogram prediction and actual observation. In conclusion, preoperative and postoperative glycemic variability is closely related to the occurrence of SSI. We developed and validated a nomogram to accurately predict the risk of SSI after TLIF surgery. It's helpful for spinal surgeons to formulate reasonable treatment plans and prevention strategies for type 2 diabetes patients.

Complications and outcomes of open posterior lumbar spinal fusion surgery in obese patients: a meta-analysis.

OBJECTIVE: The aim of this study was to determine whether obesity affects the operation, complications and outcomes after open posterior lumbar spinal fusion surgery for the treatment of low back pain and leg pain. METHODS: A meta-analysis of studies that compared the outcome of posterior lumbar spinal fusion in obese and non-obese patients. A total of 16 studies were included. RESULTS: There was no difference in pain and functional outcomes. Posterior lumbar spinal fusion in obese patients resulted in a statistically significant increase in intra-operative blood loss (weighted mean difference 40.93, 95% confidence interval (CI) 15.97-65.90, n = 243, and p=.001), longer duration of surgery (weighted mean difference -1.64, 95% CI -4.12 to 0.84, n = 1460, and p=.19), more complications (odds ratio: 1.59, 95% CI 1.24-2.05, n = 339, and p<.001) and extend length of stay (weighted mean difference 0.31, 95% CI 0.07-0.55, n = 1408, and p=.01). CONCLUSIONS: Obese patients experience more blood loss, longer duration of surgery, more complications and extended length of stay, but their back and leg pain and functional outcomes are similar to non-obese patients. Based on these results, obesity is not a contraindication to open posterior lumbar spinal fusion surgery.

Diagnostic and Therapeutic Value of Hsa_circ_0002594 for T Helper 2-Mediated Allergic Asthma.

INTRODUCTION: Circular RNAs (circRNAs) are an endogenous mircoRNA sponge that could act as potential biomarkers for the diagnosis and treatment of diseases. However, the role of circRNAs in asthma is far from clear. OBJECTIVE: The aim of this study is to assess the diagnostic and therapeutic value of hsa_circ_0002594 for T helper (Th) 2-mediated allergic asthma. METHODS: The expression profiles of hsa_circ_0002594 in CD4+ T cells were revealed by circRNA microarray. Hsa_circ_0002594 expression was confirmed via quantitative real-time PCR (qRT-PCR) in asthmatic patients and healthy subjects. Hsa_circ_0002594 levels were compared between subgroups. The clinical diagnostic abilities and therapeutic response of hsa_circ_0002594 were evaluated. The analyses utilized included a student's t test, nonparametric tests, Spearman's rank-order correlation, Fisher's exact test, and the generation of receiver operating characteristic (ROC) curves. RESULTS: Hsa_circ_0002594 was upregulated and positively correlated with fraction of exhaled nitric oxide while negatively correlated with methacholine dose producing a decrease of 20% from baseline in forced expiratory volume in the first second (PD20) in CD4+ T cells of asthma. Furthermore, hsa_circ_0002594 expression was higher in subgroups with a family history, skin pricking test (SPT)-positive, or Th2-high. The hsa_circ_0002594-high subgroup was more frequently associated with Th2-high biomarker profiles and positive SPT. Hsa_circ_0002594 was decreased after inhaled corticosteroids (ICS) treatment. ROC curve analyses of hsa_circ_0002594 showed high area under the curve values in the presence of ICS or not. CONCLUSIONS: Our data suggested that hsa_circ_0002594 was upregulated in CD4+ T cells and might have potential value in the diagnosis and treatment of Th2-mediated allergic asthma.

Gene susceptibility identification in a longitudinal study confirms new loci in the development of chronic obstructive pulmonary disease and influences lung function decline.

BACKGROUND: To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population. METHODS: Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010. Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping. Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline. And another 9SNPs were selected from HapMap website as HHIP tags. In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses. RESULTS: We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population. And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations. CONCLUSIONS: These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population. Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.

IL-33 promotes mouse keratinocyte-derived chemokine, an IL-8 homologue, expression in airway smooth muscle cells in ovalbumin-sensitized mice.

BACKGROUND: Although it is recognized that IL-33 plays a key role in the onset of asthma, it is currently unclear whether IL-33 acts on any other target cells besides mast cells and Th2 cells in asthma. We investigated that whether airway smooth muscle cells (ASMCs) could contribute to asthma via stimulation with IL-33. METHODS: To create a mouse model of acute asthma, murine ASMCs were isolated and cultured in vitro with IL-33. The ASMCs were divided into two groups, ASMCs from normal mice and ASMCs from ovalbumin-sensitized mice. The release of mouse KC was analyzed by PCR and ELISA. Immunocytochemical Staining of murine ASMCs for ST2 and IL-1RAcP was performed. RESULTS: IL-33 promoted KC expression, both in terms of mRNA and protien levels, in ASMCs from ovalbumin-sensitized mice. ST2 and IL-1RAcP were expressed in the membrane of ASMCs in ovalbumin-sensitized mice. CONCLUSION: IL-33 may contribute to the inflammation in the airways by acting on airway smooth muscle cells. IL-33 and ST2 may play important roles in allergic bronchial asthma.

Regulatory mechanism of perinatal nonylphenol exposure on cardiac mitochondrial autophagy and the PINK1/Parkin signaling pathway in male offspring rats.

OBJECTIVE: This study investigated whether perinatal exposure to nonylphenol (NP) induces mitochondrial autophagy (i.e., mitophagy) damage in neonatal rat cardiomyocytes (NRCMs) and whether the PINK1/Parkin signaling pathway is involved in NP-induced primary cardiomyocyte injury. METHODS AND RESULTS: In vivo: Perinatal NP exposure increased apoptosis and mitochondrial damage in NRCMs. Mitochondrial swelling and autophagosome-like structures with multiple concentric membranes were observed in the 100 mg/kg NP group, with an increase in the number of autophagosomes. Disorganized fiber arrangement and elevated serum myocardial enzyme levels were observed with increasing NP dosage. Additionally, NP exposure led to increased MDA levels and decreased SOD activity and ATP levels in myocardial tissue. The mRNA expression levels of autophagy-related genes, including Beclin-1, p62, and LC3B, as well as the expression of mitochondrial autophagy-related proteins (PINK1, p-Parkin, Parkin, Beclin-1, p62, LC3-I, LC3-II, and LC3-II/I) and apoptosis-related proteins (Bax and caspase-3), increased, whereas the expression levels of the mitochondrial membrane protein TOMM20 and the anti-apoptotic protein Bcl-2 decreased. In vitro: NP increased ROS levels, LDH release, and decreased ATP levels in NRCMs. CsA treatment significantly inhibited the expression of autophagy-related proteins (Beclin-1, LC3-II/I, and p62) and apoptosis-related proteins (caspase-3 and Bax), increased the expression levels of TOMM20 and Bcl-2 proteins, increased cellular ATP levels, and inhibited LDH release. The inhibition of the PINK1/Parkin signaling pathway suppressed the expression of mitochondrial autophagy-related proteins (PINK1, p-Parkin, Parkin, Beclin-1, LC3-II/I, and p62) and apoptosis-related proteins (caspase-3 and Bax), increased TOMM20 and Bcl-2 protein expression, increased ATP levels, and decreased LDH levels in NRCMs. CONCLUSIONS: This study is novel in reporting that perinatal NP exposure induced myocardial injury in male neonatal rats, thereby inducing mitophagy. The PINK1/Parkin signaling pathway was involved in this injury by regulating mitophagy.

Amelioration of nonylphenol-induced anxiety/depression-like behaviors in male rats using green tea and Zn-Se tea interventions.

Objective: This study aimed to investigate the effects of exposure to nonylphenol (NP) on anxiety/depression-like behaviors in rats and alleviation of those effects via green tea and zinc selenium (Zn-Se) tea interventions. Material and Methods: Totally, 40 male specific-pathogen free (SPF) Sprague-Dawley (SD) male rats were randomly divided into four groups (n = 10 rats per group): control group (5 ml/kg corn oil), NP group (40 mg/kg NP), NP + GT group (40 mg/kg NP + 1 g/kg/day green tea), and NP + Zn-Se tea group (40 mg/kg NP + 1 g/kg/day ZST). All dose-based groups received oral gavage of either corn oil or drugs over a 6-month period: NP at a dosage of 40 mg/kg/day was administered to rats for the initial 3 months, followed by a combination of NP with green tea and NP with Zn-Se tea for the subsequent 3 months. Results: Tea intervention resulted in weight loss in rats. The hippocampal tissue NP level in the tea group was slightly lower than that in the NP group. Following tea intervention, compared with the NP group, the residence time in the light-dark box test was shortened PGT = 0.048, P < 0.001), and the number of entries into the closed arm in the elevated plus maze test in the tea-treated group was significantly reduced. In addition, the immobility time in the central square in the open field test decreased. The sucrose preference index score in the sucrose preference test increased, and the immobility time in the forced swimming test was reduced (PGT = 0.049, PZST < 0.001). The effects of Zn-S e tea were superior to green tea. The damage to the hippocampal tissues in the group treated with tea was less than that in the NP group. The cellular arrangement was tighter with degeneration, deepstaining, and pyknotic nerve cells were visible. The nuclei in the NP group were atrophied, and the cells were sparsely arranged. Compared with the control group, serum brain-derived neurotrophic factor (BDNF) level was lower in the NP group. The serum corticosterone level in the NP group was elevated. Compared with the NP group, serum corticosterone level was reduced in the NP + Zn-Se tea group. Conclusion: Chronic NP exposure induced anxiety/depression-like behaviors in rats. Green tea effectively reduced the damage to the hippocampus and prefrontal cortex induced by NP. The effects of Zn-Se tea were slightly more noticeable than those of conventional green tea. Highlights: 1) Chronic NP exposure induced anxiety/depression-like behaviors in rats.2) Zn-Se tea reduced the damage of hippocampal and prefrontal cortex induced by NP.3) NP-induced depression accompanied by the changes of BDNF, CORT and neuropathology.

Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

Development of simultaneous quantitation method for 20 free advanced glycation end products using UPLC-MS/MS and clinical application in kidney injury.

Advanced glycation end products (AGEs), derived from the non-enzymatic glycation reaction, are defined as glycotoxins in various diseases including aging, diabetes and kidney injury. Exploring AGEs as potential biomarkers for these diseases holds paramount significance. Nevertheless, the high chemical structural similarity and great heterogeneity among AGEs present a formidable challenge when it comes to the comprehensive, simultaneous, and accurate detection of multiple AGEs in biological samples. In this study, an UPLC/MS/MS method for simultaneous quantification of 20 free AGEs in human serum was firstly established and applied to quantification of clinical samples from individuals with kidney injury. Simple sample preparation method through protein precipitation without derivatization was used. Method performances including imprecision, accuracy, sensitivity, linearity, and carryover were systematically validated. Intra- and inter- imprecision of 20 free AGEs were 1.93-5.94 % and 2.30-8.55 %, respectively. The method accuracy was confirmed with good recoveries ranging from 96.40 % to 103.25 %. The LOD and LOQ were 0.1-3.13 ng/mL and 0.5-6.25 ng/mL, respectively. Additionally, the 20 free AGEs displayed excellent linearity (R2 >0.9974) across a wide linear range (1.56-400 ng/mL). Finally, through simultaneous quantitation of 20 Free AGEs in 100 participants including kidney injury patient and healthy controls, we identified six free AGEs, including N6-carboxyethyl-L-arginine (CEA), N6-carboxymethyl-L-lysine (CML), methylglyoxal-derived hydroimidazolones (MG-H), N6-formyl-lysine, N6-carboxymethyl-L-arginine (CMA), and glyoxal-derived hydroimidazolone (G-H), could well distinguish kidney injury patients and healthy individuals. Among them, the levels of four free AGEs including CML, CEA, MG-H, and G-H strongly correlate with traditionally clinical markers of kidney disease. The high area under the curve (AUC) values (AUC=0.965) in receiver operating characteristic (ROC) curve indicated that these four free AGEs can be served as combined diagnostic biomarkers for the diagnosis of kidney disease.

METTL14 Regulates PLAGL2/ß-Catenin Signaling Axis to Promote the Development of Nonsmall Cell Lung Cancer.

N6-methyladenosine (m6A) is an abundant eukaryotic mRNA modification involved in regulating the formation and metastasis of nonsmall cell lung cancer (NSCLC). We collected clinical NSCLC tissue and paracarcinoma tissue. Then methyltransferase-like 14 (METTL14), pleomorphic adenoma gene like-2 (PLAGL2), and ß-catenin expressions were assessed using quantitative real-time PCR and western blot. PLAGL2, and ß-catenin (nuclear) expressions were increased in NSCLC tissues. Cell proliferation, migration, invasion, and death were examined. PLAGL2 could activate ß-catenin signaling to affect cell proliferation and migration abilities. RNA immunoprecipitation assay was operated to identify m6A modification levels of PLAGL2 after knockdown and overexpression of METTL14. PLAGL2 was regulated by METTL14-mediated m6A modification. Knockdown of METTL14 repressed cell proliferation, migration, and invasion, and promoted cell death. Interestingly, these effects were reversed when PLAGL2 was overexpressed. Finally, tumor formation in nude mice was performed to verify the role of the METTL14/PLAGL2/ß-catenin signaling axis. Tumor formation in nude mice demonstrated METTL14/PLAGL2/ß-catenin axis promoted NSCLC development in vivo. In brief, METTL14 promoted NSCLC development by increasing m6A methylation of PLAGL2 to activate ß-catenin signaling. Our research provided essential clues for in-depth comprehension of the mechanism of NSCLC occurrence and development and also provided the basis for NSCLC treatment.

[Clinical research progress of spinal epidural lipomatosis].

Objective: To review the clinical research progress of spinal epidural lipomatosis (SEL). Methods: The clinical studies on SEL at home and abroad in recent years were extensively reviewed, and the pathogenesis, clinical and imaging manifestations, and treatment status of SEL were summarized and analyzed. Results: SEL is a disease characterized by compression of the spinal cord and nerve roots due to abnormal accumulation of epidural adipose tissue in the spinal canal. Its prevalence and diagnosis rate are low and the pathogenesis is not fully understood. MRI is the most sensitive and specific diagnostic test for SEL. Surgical decompression and removal of excess adipose tissue are the only options for patients with acute SEL or those who have failed conservative management, and conservative management should be considered for other patients. Conclusion: SEL is a rare disease and related research still needs to be improved. In the future, high-quality, multi-center and large-sample studies will be of great significance for evaluating the choice of treatment methods and effectiveness of SEL patients.

Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway. / 间å 质干细胞移植治疗的新视角：靶向铁死亡通路.

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.

Collateral Status and Clinical Outcomes after Mechanical Thrombectomy in Patients with Anterior Circulation Occlusion.

BACKGROUND: Successful mechanical thrombectomy (MT) requires reliable, noninvasive selection criteria. We aimed to investigate the association of collateral status and clinical outcomes after MT in patients with ischemic stroke due to anterior circulation occlusion. METHODS: 109 patients with poor collaterals and 110 aged, sex-matched patients with good collaterals were enrolled in the study. Collateral circulation was estimated by the CT angiography with a 0-3 scale. The collateral status was categorized as poor collaterals (scores 0-1) and good collaterals (scores 2-3). The reperfusion was assessed by the modified Treatment in Cerebral Infarction scale (mTICI, score 0/1/2a/2b/3). The clinical outcomes included the scores on the modified Rankin scale (mRS, ranging from 0 to 6) and death 90 days after mechanical thrombectomy. RESULTS: Patients with greater scores of collateral status were more likely to achieve successful reperfusion (mTICI 2b/3). Patients with good collaterals were significantly associated with a higher chance of achieving mRS of 0-1 at 90 days (adjusted ORs: 4.55; 95% CI: 3.17-7.24; and P < 0.001) and a lower risk of death at 90 days (adjusted ORs: 0.87; 95% CI: 4.0%-28.0%; and P = 0.012) compared to patients with poor collaterals. In subgroup analyses, patients with statin use seem to benefit more from the effect of collateral status on good mRS (≤2). CONCLUSION: Among patients with acute ischemic stroke caused by anterior circulation occlusion, better collateral status is associated with higher scores on mRS and lower mortality after mechanical thrombectomy. Statin use might have an interaction with the effect of collateral status.