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Natural pyrethrins (NPs), one kind of bio-pesticide, have been widely used in organic agriculture and ecological environment studies. Studies have shown that NPs may affect the metabolism of rat liver and human hepatocytes; nevertheless, the toxic effects of NPs on the liver and the related mechanisms are still incompletely understood. In this research, we utilized three types of human liver cells to investigate the mechanism of NPs' induction of oxidative stress. The results showed that NPs exhibit noteworthy cytotoxic effects on human liver cells. These effects are characterized by the induction of LDH release, mitochondrial collapse, and an increased production of ROS and MDA content, subsequently activating the Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2- related factor 2 (Keap1/Nrf-2) pathway. The ROS inhibitor N-acetyl-L-cysteine (NAC) can alleviate ROS/Nrf2-mediated oxidative stress. In addition, the siRNA knockdown of Nrf-2 exacerbated the injury, including ROS production, and inhibited cell viability. In summary, the ROS-mediated Keap1/Nrf-2 pathway could be an important regulator of NP-induced damage in human liver cells, which further illustrates the hepatotoxicity of NPs and thereby contributes to the scientific basis for further exploration.
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Our research investigated the effects of hsa-miR-134-5p on glioma progression, focusing on its interaction with the BDNF/ERK signaling pathway. U251 and U87 cell lines were analyzed post-transfection with hsa-miR-134-5p mimics and inhibitors, confirming the miRNA's binding to BDNF using dual luciferase assays. Q-PCR was employed to measure expression changes, revealing that hsa-miR-134-5p markedly inhibited glioma cell proliferation, migration, and invasion, as evidenced by CCK8, monoclonal formation, and Transwell assays. Scratch tests and Western blotting demonstrated hsa-miR-134-5p's modulation of the BDNF/ERK pathway and associated decrease in MMP2/9 protein levels. Flow cytometry suggested that hsa-miR-134-5p might also block the G0/S phase transition. In vivo studies using nude mice corroborated the tumor-suppressing effects of hsa-miR-134-5p, which were negated by elevated BDNF levels. Comparative protein analysis across groups confirmed the pathway's significance in tumorigenesis. Our findings identify hsa-miR-134-5p as a key molecule impeding glioma cell growth by curtailing the BDNF/ERK pathway, with the reversal by BDNF upregulation pointing to the potential of therapeutically exploiting the hsa-miR-134-5p/BDNF axis in glioma care.
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Fator Neurotrófico Derivado do Encéfalo , Movimento Celular , Proliferação de Células , Glioma , Sistema de Sinalização das MAP Quinases , Camundongos Nus , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Glioma/patologia , Glioma/metabolismo , Glioma/genética , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Animais , Linhagem Celular Tumoral , Camundongos , Regulação Neoplásica da Expressão Gênica , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genéticaRESUMO
After surgical or natural menopause, women face a high risk of nonalcoholic fatty liver disease (NAFLD), which can be diminished by hormone replacement therapy (HRT). The gut microbiota is subject to modulation by various physiological changes and the progression of diseases. This microbial ecosystem coexists symbiotically with the host, playing pivotal roles in immune maturation, microbial defense mechanisms, and metabolic functions essential for nutritional and hormone homeostasis. E2 supplementation effectively prevented the development of NAFLD after bilateral oophorectomy (OVX) in female rats. The changes in the gut microbiota such as abnormal biosynthetic metabolism of fatty acids caused by OVX were partially restored by E2 supplementation. The combination of liver transcriptomics and metabolomics analysis revealed that linoleic acid (LA) metabolism, a pivotal pathway in fatty acids metabolism was mainly manipulated during the induction and treatment of NAFLD. Further correlation analysis indicated that the gut microbes were associated with abnormal serum indicators and different LA metabolites. These metabolites are also closely related to serum indicators of NAFLD. An in vitro study verified that LA is an inducer of hepatic steatosis. The changes in transcription in the LA metabolism pathway could be normalized by E2 treatment. The metabolic perturbations of LA may directly and secondhand impact the development of NAFLD in postmenopausal individuals. This research focused on the sex-specific pathophysiology and treatment of NAFLD, providing more evidence for HRT and calling for the multitiered management of NAFLD.
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Tumor treating fields (TTFields) therapy is a novel and effective noninvasive cancer therapy, and it has been approved by FDA in the treatment of recurrent and newly diagnosed glioblastoma, and malignant pleural mesothelioma. Moreover, TTFields therapy has been widely studied in both clinical trials and preclinical studies in recent years. Based on its high efficacy, research on TTFields therapy has been a hot topic. Thus, the authors made this scientometric analysis of TTfields to reveal the scientometric distributions such as annual publications and citations, countries and institutions, authors, journals, references, and more importantly, research status and hot topics of the field. In recent years, publication numbers have been stable at high values, and citation numbers have been increasing greatly. The United States and Israel were the top two countries with the highest publication numbers, followed by Germany and Switzerland. Scientometric analyses of keywords indicated that clinical applications and antitumor mechanisms are probably the two main parts of current research on TTfields. Most clinical trials of TTfields focus on the treatment of glioblastoma. And a variety of other cancers such as lung cancer especially nonsmall cell lung cancer, hepatic cancer, other brain tumors, etc. have also been studied in both clinical trials and preclinical studies.
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Bibliometria , Humanos , Terapia por Estimulação Elétrica , Glioblastoma/terapia , Neoplasias/terapiaRESUMO
DNA methylation plays a crucial role in the regulation of plant growth and the biosynthesis of secondary metabolites. Danshen (Salvia miltiorrhiza) is a valuable Chinese herbal medicine commonly used to treat cardiovascular diseases; its active ingredients are tanshinones and phenolic acids, which primarily accumulate in roots. Here, we conducted a targeted metabolic analysis of S. miltiorrhiza roots at 3 distinct growth stages: 40 d old (r40), 60 d old (r60), and 90 d old (r90). The contents of tanshinones (cryptotanshinone, tanshinone I, tanshinone IIA, and rosmariquinone) and phenolic acids (rosmarinic acid and salvianolic acid B) gradually increased during plant development. Whole-genome bisulfite sequencing and transcriptome sequencing of roots at the 3 growth stages revealed an increased level of DNA methylation in the CHH context (H represents A, T, or C) context at r90 compared with r40 and r60. Increased DNA methylation levels were associated with elevated expression of various genes linked to epigenetic regulations, including CHROMOMETHYLASE2 (SmCMT2), Decrease in DNA Methylation 1 (SmDDM1), Argonaute 4 (SmAGO4), and DOMAINS REARRANGED METHYLTRANSFERASE 1 (SmDRM1). Moreover, expression levels of many genes involved in tanshinone and salvianolic acid biosynthesis, such as copalyldiphosphate synthase 5 (SmCPS5), cytochrome P450-related enzyme (SmCYP71D464), geranylgeranyl diphosphate synthase (SmGGPPS1), geranyl diphosphate synthase (SmGPPS), hydroxyphenylpyruvate reductase (SmHPPR), and hydroxyphenylpyruvate dioxygenase (SmHPPD), were altered owing to hyper-methylation, indicating that DNA methylation plays an important role in regulating tanshinone and phenolic acid accumulation. Our data shed light on the epigenetic regulation of root growth and the biosynthesis of active ingredients in S. miltiorrhiza, providing crucial clues for further improvement of active compound production via molecular breeding in S. miltiorrhiza.
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Abietanos , Hidroxibenzoatos , Salvia miltiorrhiza , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Metilação de DNA , Epigênese Genética , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Glioma, the predominant form of central nervous system (CNS) malignancies, presents a significant challenge due to its high prevalence and low 5-year survival rate. The efficacy of current treatment methods is limited by the presence of the blood-brain barrier, the immunosuppressive microenvironment, and other factors. Immunotherapy has emerged as a promising approach, as it can overcome the blood-brain barrier. A tumor's immune privilege, which is induced by an immunosuppressive environment, constricts immunotherapy's clinical impact in glioma. Pyroptosis, a programmed cell death mechanism facilitated by gasdermins, plays a significant role in the management of glioma. Its ability to initiate and regulate tumor occurrence, progression, and metastasis is well-established. However, it is crucial to note that uncontrolled or excessive cell death can result in tissue damage, acute inflammation, and cytokine release syndrome, thereby potentially promoting tumor advancement or recurrence. This paper aims to elucidate the molecular pathways involved in pyroptosis and subsequently discuss its induction in cancer therapy. In addition, the current treatment methods of glioma and the use of pyroptosis in these treatments are introduced. It is hoped to provide more ideas for the treatment of glioma.
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Glioma , Piroptose , Humanos , Glioma/terapia , Apoptose , Morte Celular , Imunoterapia , Imunossupressores , Microambiente TumoralRESUMO
BACKGROUND: Deep vein thrombosis (DVT) of the lower extremity is one of the most common postoperative complications, especially after craniocerebral surgery. DVT may lead to pulmonary embolism, which has a devastating impact on patient prognosis. This study aimed to investigate the incidence and risk factors of DVT in the lower limbs following craniocerebral surgery. AIM: To identify independent risk factors for the development of postoperative DVT and to develop an effective risk prediction model. METHODS: The demographic and clinical data of 283 patients who underwent craniocerebral surgery between December 2021 and December 2022 were retrospectively analyzed. The independent risk factors for lower extremity DVT were identified by univariate and multivariate analyses. A nomogram was created to predict the likelihood of lower extremity DVT in patients who had undergone craniocerebral surgery. The efficacy of the prediction model was determined by receiver operating characteristic curve using the probability of lower extremity DVT for each sample. RESULTS: Among all patients included in the analysis, 47.7% developed lower extremity DVT following craniocerebral surgery. The risk of postoperative DVT was higher in those with a longer operative time, and patients with intraoperative intermittent pneumatic compression were less likely to develop postoperative DVT. CONCLUSION: The incidence of lower extremity DVT following craniocerebral surgery is significant, highlighting the importance of identifying independent risk factors. Interventions such as the use of intermittent pneumatic compression during surgery may prevent the formation of postoperative DVT.
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Premature menopause is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). Menopausal hormone therapy (MHT) has been widely used in clinical practice and has the potential to protect mitochondrial function and alleviate NAFLD. After bilateral oophorectomy (OVX), female rats without 17ß-estradiol (E2) intervention developed NAFLD, whereas E2 supplementation was effective in preventing NAFLD in female rats. The altered pathways and cellular events from both comparison pairs, namely, the OVX vs. sham group and the OVX vs. E2 group, were assessed using transcriptomic analysis. KEGG pathways enriched by both transcriptomic and metabolomic analyses strongly suggest that oxidative phosphorylation is a vital pathway that changes during the development of NAFLD and remains unchanged when E2 is applied. Liver tissue from the OVX-induced NAFLD group exhibited increased lipid peroxidation, impaired mitochondria, and downregulated ERα/SIRT1/PGC-1α expression. An in vitro study indicated that the protective effect of E2 treatment on hepatic steatosis could be abolished when ERα or SIRT1 was selectively inhibited. This damage was accompanied by reduced mitochondrial complex activity and increased lipid peroxidation. The current research indicates that E2 upregulates the ERα/SIRT1/PGC-1α signaling pathway and protects mitochondrial function to prevent OVX-induced NAFLD.
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Plant-derived natural products are a specific class of active substances with numerous applications in the medical, energy, and industrial fields. Many of these substances are in high demand and have become the fundamental materials for various purposes. Recently, the use of synthetic biology to produce plant-derived natural products has become a significant trend. Plant chassis, in particular, offer unique advantages over microbial chassis in terms of cell structure, product affinity, safety, and storage. The development of the plant hairy root tissue culture system has accelerated the commercialization and industrialization of synthetic biology in the production of plant-derived natural products. This paper will present recent progress in the synthesis of various plant natural products using plant chassis, organized by the types of different structures. Additionally, we will summarize the four primary types of plant chassis used for synthesizing natural products from plant sources and review the enabling technologies that have contributed to the development of synthetic biology in recent years. Finally, we will present the role of isolated and combined use of different optimization strategies in breaking the upper limit of natural product production in plant chassis. This review aims to provide practical references for synthetic biologists and highlight the great commercial potential of plant chassis biosynthesis, such as hairy roots.
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Produtos Biológicos , Produtos Biológicos/metabolismo , Plantas/metabolismo , Biologia SintéticaRESUMO
Salvia miltiorrhiza and Salvia prattii seeds are rich in metabolites that are beneficial to human health and can be utilised as nutritional supplements. In this study, UPLC-MS and GC-MS based on extensively focused metabolomics were used to compare the seed metabolomics of the two species. LC-MS detected 118 metabolites, primarily Lipids and phenylpropanoids. GC- MS detected a total of 188 metabolites, mainly organic acids and their derivatives, of which Salvia prattii seeds contain high levels of nutrients. In addition, we experimentally determined antioxidant activity of two Salvia species, and the results showed that the antioxidant activity of Salvia prattii seeds was about twice as high as that of Salvia miltiorrhiza seeds. We used WGCNA to group the metabolites, and found the central metabolites in the focal modules including flavonoids and terpenoids. Our study contributes valuable knowledge for future research on the chemical makeup of Salvia prattii seeds.
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Polycystic ovary syndrome (PCOS) is a prevalent reproductive endocrine disorder, with metabolic abnormalities and ovulation disorders. The post-translational modifications (PTMs) are functionally relevant and strengthen the link between metabolism and cellular functions. Lysine crotonylation is a newly identified PTM, the function of which in PCOS has not yet been reported. To explore the molecular mechanisms of crotonylation involved in the abnormalities of metabolic homeostasis and oocyte maturation in PCOS, by using liquid chromatography-tandem mass spectrometry analysis, we constructed a comprehensive map of crotonylation modifications in ovarian tissue of PCOS-like mouse model established by dehydroepiandrosterone induction. The crotonylation levels of proteins involved in metabolic processes were significantly decreased in PCOS ovaries compared to control samples. Further investigation showed that decrotonylation of Lon protease 1 (LONP1) at lysine 390 was associated with mitochondrial dysfunction in PCOS. Moreover, LONP1 crotonylation levels in PCOS were correlated with ovarian tissue oxidative stress levels, androgen levels, and oocyte development. Consistently, down-regulation of LONP1 and LONP1 crotonylation levels were also observed in the blood samples of PCOS patients. Collectively, our study revealed a mechanism by which the decrotonylation of LONP1 may attenuate its activity and alter follicular microenvironment to affect oocyte maturation in PCOS.
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BACKGROUND: This multi-center, cross-sectional study intended to explore the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with polycystic ovary syndrome (PCOS). METHODS: Patients who met the PCOS Rotterdam diagnostic criteria were enrolled in 6 centers in China, and age-matched healthy volunteers were also recruited. Data were collected including medical history, physical characteristics, and blood tests (liver function, blood lipids, blood glucose and insulin, sex hormones, etc.). Transvaginal or transrectal ultrasound was employed to identify polycystic ovarian morphology (PCOM). The serological score Liver Fat Score (LFS) >-0.640 was used for the diagnosis of NAFLD, and the diagnosis of MAFLD was made according to the 2020 new definition. RESULTS: A total of 217 PCOS patients and 72 healthy controls were included. PCOS patients had impaired glucose and lipid metabolism, higher liver enzymes and LFS. Both NAFLD (33.6%) and MAFLD (42.8%) was more prevalent in PCOS patients than in controls (4.2%, P < 0.001). Logistic regression results showed that HOMA-IR ≥ 3.54 and ALT ≥ 18.2 were independently associated with NAFLD (P < 0.001) and MAFLD (P ≤ 0.001). The prevalence of NAFLD was significantly higher in PCOS patients with free androgen index (FAI) > 8 (53.8% versus 17.4%, P < 0.001) and BMI ≥ 24 kg/m2 (57.3%, 11.3%, P < 0.001). CONCLUSION: The prevalence of NAFLD/MAFLD in PCOS patients was significantly higher than that in healthy controls and was independently associated with HOMA-IR and ALT. PCOS patients with overweight and elevated FAI have a higher prevalence of fatty liver.
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Hepatopatia Gordurosa não Alcoólica , Síndrome do Ovário Policístico , Humanos , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Estudos Transversais , Fatores de RiscoRESUMO
The aim of this research was to study the combined effects of bisphenols and iodine exposure on the thyroid gland during pregnancy. We included 162 pregnant women from a cohort established in Shanghai. Urinary concentrations of bisphenol A, bisphenol B(BPB), bisphenol C(BPC), bisphenol F, bisphenol S, and bisphenol AF(BPAF) were examined. Bayesian kernel machine regression (BKMR) and quantile g-computation models were used. The geometric means of BPA, BPB, BPC, BPF, BPS, BPAF, and ΣBPs levels in urine were 3.03, 0.24, 2.66, 0.36, 0.26, 0.72, and 7.55 µg/g creatinine, respectively. We observed a positive trend in the cumulative effects of BPs and iodine on serum triiodothyronine (FT3) and free thyroxine (FT4), as well as a U-shaped dose-response relationship between BPs and the probability of occurrence of thyroperoxidase autoantibody positivity in women with low urinary iodine concentration. In addition, a synergistic effect on the probability of occurrence of thyroid autoantibody positivity was observed between BPF and BPB, as well as between BPC and BPAF in this study. There were adverse health effects on the thyroid after co-exposure to BPs and iodine. Even if pregnant women were exposed to lower levels of BPs, women with iodine deficiency remained vulnerable to thyroid autoimmune disease.
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Compostos Benzidrílicos , Exposição Materna , Fenóis , Glândula Tireoide , Humanos , Feminino , Gravidez , Poluentes Ocupacionais do Ar , Compostos Benzidrílicos/urina , Fenóis/urina , Exposição Materna/efeitos adversos , Glândula Tireoide/efeitos dos fármacos , China , Tri-Iodotironina/sangue , Tri-Iodotironina/efeitos dos fármacos , Tiroxina/sangue , Tiroxina/efeitos dos fármacos , AdultoRESUMO
BACKGROUND: Gliomas, originating from glial cells within the brain or spinal cord, are common central nervous system tumors with varying degrees of malignancy that influence the complexity and difficulty of treatment. The current strategies, including traditional surgery, radiotherapy, chemotherapy, and emerging immunotherapies, have yielded limited results. As such, our study aims to optimize risk stratification for a more precise treatment approach. We primarily identify feature genes associated with poor immune cell infiltration patterns through various omics algorithms and categorize glioma patients based on these genes to enhance the accuracy of patient prognosis assessment. This approach can underpin individualized treatment strategies and facilitate the discovery of new therapeutic targets. METHODS: We procured datasets of gliomas and normal brain tissues from TCGA, CGGA, and GTEx databases. Clustering was conducted using the input of 287 immune cell feature genes. Hub genes linked with the poor prognosis subtype (C1) were filtered through WGCNA. The TCGA dataset served as the discovery cohort and the CGGA dataset as the external validation cohort. We constructed a prognostic model related to feature genes from poor immune cell infiltration patterns utilizing LASSO-Cox regression. Comprehensive analyses of genomic heterogeneity, tumor stemness, pathway relevance, immune infiltration patterns, treatment response, and potential drugs were conducted for different risk groups. Gene expression validation was performed using immunohistochemistry (IHC) on 98 glioma samples and 11 normal brain tissue samples. RESULTS: Using the filtered immune cell-related genes, glioma patients were stratified into C1 and C2 subtypes through clustering. The C1 subtype exhibited a worse prognosis, with upregulated genes primarily enriched in immune response, extracellular matrix, etc., and downregulated genes predominantly enriched in neural signal transduction and neural pathway-related aspects. Seven advanced algorithms were used to elucidate immune cell infiltration patterns of different subtypes. In addition, WGCNA identified hub genes from poor immune infiltration patterns, and a prognostic model was constructed accordingly. High-risk patients demonstrated shorter survival times and higher risk scores as compared to low-risk patients. Multivariate Cox regression analysis revealed that, after adjusting for confounding clinical factors, risk score was a vital independent predictor of overall survival (OS) (P < 0.001). The established nomogram, which combined risk scores with WHO grade and age, accurately predicted glioma patient survival rates at 1, 3, and 5 years, with AUCs of 0.908, 0.890, and 0.812, respectively. This risk score enhanced the nomogram's reliability and informed clinical decision-making. We also comprehensively analyzed genomic heterogeneity, tumor stemness, pathway relevance, immune infiltration patterns, treatment response, and potential drugs for different risk groups. In addition, we conducted preliminary validation of the potential PLSCR1 gene using IHC with a large sample of gliomas and normal brain tissues. CONCLUSION: Our optimized risk stratification strategy for glioma patients has the potential to improve the accuracy of prognosis assessment. The findings from our omics research not only enhance the understanding of the functions of feature genes related to poor immune cell infiltration patterns but also offer valuable insights for the study of glioma prognostic biomarkers and the development of individualized treatment strategies.
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Background: The incidence of meningioma is disparate to sex: meningiomas are more common in women than in men, especially in middle-aged women. Understanding the epidemiology and survival of middle-aged women with meningiomas would help estimate their public health impacts and optimize risk stratification. Methods: Data on middle-aged (35-54 years) female patients with meningiomas between 2004 and 2018 were obtained from the SEER database. Age-adjusted incidence rates per 100 000 population-years were calculated. Kaplan-Meier and multivariate Cox proportional hazard models were utilized in the overall survival (OS) analysis. Results: Data from 18302 female patients with meningioma were analyzed. The distribution of patients increased with age. Most patients were White and non-Hispanic, according to race and ethnicity, respectively. Over the past 15 years, non-malignant meningiomas have shown an increasing trend; however, malignant meningiomas have shown an opposite trend. Older age, Black population, and large non-malignant meningiomas tend to have worse prognoses. Surgical resection improves OS, and the extent of resection is a critical prognostic factor. Conclusions: This study observed an increase in non-malignant meningiomas and a decrease in the incidence of malignant meningiomas in middle-aged females. The prognosis deteriorated with age, in Black people, and with large tumor size. Additionally, the extent of tumor excision was found to be a significant prognostic factor.
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Bisphenol A (BPA) substitutes, such as bisphenol S (BPS) and bisphenol AF (BPAF), are increasingly used due to restrictions on BPA usage, a known endocrine disrupting chemical and putative obesogen. However, little is known about the obesogenic effects of exposure to BPA substitutes in children. A total of 426 children aged 7 years old originally recruited from Laizhou Wan Birth Cohort in Shandong, China, during 2010-2013 participated in the 2019-2020 survey. Urinary BPA and its substitutes including BPS, BPAF, bisphenol B (BPB), bisphenol AP (BPAP), bisphenol Z (BPZ), and bisphenol P (BPP) were determined. Anthropometric measures including height, weight, waist circumference, and body fat percentage were assessed, and overweight/obesity was defined as BMI z-score ≥ 85th percentile. Linear and logistic regressions were used on continuous and binary obesity measures, respectively, and weighted quantile sum (WQS) regression was further used to estimate the mixture effects of exposure to diverse bisphenols, and sex-stratified analysis was performed. BPA substitutes were widely detected (> 75%) in children's urine samples. A positive association with obesity measures was consistently observed for urinary BPS and BPAF, i.e., BMI z-score, waist circumference, and overweight/obesity. Further analysis from the WQS regression model demonstrated a positive association between bisphenol mixtures and all measures of obesity, with BPAF contributing the greatest weighing to the observed associations. Sex difference might exist as the positive associations were only significant in boys. No significant association was found between obesity and BPA or other BPA substitutes. Our study adds to mounting evidence that BPA substitutes BPS and BPAF are linked to obesity in children, especially in boys. Further longitudinal studies with larger sample size with continued biomonitoring these chemicals and their obesogenic effects are necessary.
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Obesidade Infantil , Humanos , Masculino , Criança , Feminino , Obesidade Infantil/induzido quimicamente , Obesidade Infantil/epidemiologia , Estudos Transversais , Sobrepeso , Compostos Benzidrílicos/análise , China/epidemiologiaRESUMO
Background: Understanding the epidemiology and prognostic factors of low-grade gliomas (LGGs) can help estimate the public health impact and optimize risk stratification and treatment strategies. Methods: 3 337 patients diagnosed with LGGs were collected from the Surveillance, Epidemiology, and End Results (SEER) dataset, 2004-2019. The incidence trends of LGGs were analyzed by patient demographics (sex, age, race, and ethnicity). In addition, a competing risk regression model was used to explore the prognostic factors of LGGs by patient demographics, tumor characteristics (histological subtypes, invasiveness, and size), treatment modality, and molecular markers (IDH mutation and 1p/19q codeletion). Results: LGGs occurred more frequently in male, non-Hispanic, and White populations. The incidence rate of mixed gliomas was stable from 2004 to 2013 and decreased dramatically to nearly zero until 2019. The risk of death increased 1.99 times for every 20-year increase in patient age, and 60 years is a predictive cut-off age for risk stratification of LGGs. Male patients showed poorer LGG-specific survival. Among the different subtypes, astrocytoma has the worst prognosis, followed by mixed glioma and oligodendroglioma. Tumors with larger size (≥5 cm) and invasive behavior tended to have poorer survival. Patients who underwent gross total resection had better survival rates than those who underwent subtotal resection. Among the different treatment modalities, surgery alone had the best survival, followed by surgery + radiotherapy + chemotherapy, but chemotherapy alone had a higher death risk than no treatment. Furthermore, age, invasiveness, and molecular markers were the most robust prognostic factors. Conclusion: This study reviewed the incidence trends and identified several prognostic factors that help clinicians identify high-risk patients and determine the need for postoperative treatment according to guidelines.
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BACKGROUND: An inflammatory myofibroblastic tumor (IMT) occurring in the central nervous system is very rare, and thus its pathogenesis is unknown. This case report and literature review aimed to explore the pathogenesis, clinical features, imaging findings, pathological characteristics, immunohistochemical characteristics, diagnoses, treatments, and risks of postoperative recurrence of IMT in the central nervous system. CASE SUMMARY: A 67-year-old woman was admitted to the hospital with an exophthalmic protrusion and double vision in the left eye that had persisted for 3 mo. Magnetic resonance imaging (MRI) showed a 2.4 cm × 1.3 cm heterogeneous large mass in the bottom of the left anterior cranial fossa, which was closely related to the dura mater. Before surgery, we suspected the mass to be meningioma. The entire mass was successfully removed under neuronavigation and electrophysiological monitoring, and postoperative pathology indicated an IMT with extensive infiltration of chronic inflammatory cells and scattered multinucleated giant cells. Head MRI at the 3-mo follow-up showed that the tumor at the bottom of left anterior cranial fossa had been completely resected without recurrence. CONCLUSION: From the histological, immunohistochemical, and genetic analyses, the present case suggests that the pathogenesis of IMT-CNS is related to autoimmunity.
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Background: Epithelial-mesenchymal transition (EMT) is a key factor in the invasion and migration of glioma cells, and the study of EMT in gliomas has become a hot topic over the past decade. Scientometric analysis is gaining more attention since it can obtain hot topics and emerging trends in a research field. This article analyzed the research related to EMT in gliomas for the first time, including descriptions of research situations, evaluations of research foci, and predictions of emerging trends. Methods: We searched the topic-related original articles from January 2012 to December 2021 in the Web of Science Core Collection (WoSCC) by using a specific strategy, and a total of 1,217 publications were obtained. The WoS platform, VOS viewer, and CiteSpace were used to analyze the annual distribution of publications and citations, authors and density of keywords, and other analyses including countries, institutions, references, clustering, burst analysis, and the timeline view of keywords. Results: Scientometric analysis identified that the study of EMT in gliomas has developed fast and received continuous attention in the last decade. Based on the results of data analysis, most publications on the topic came from China, and the United States had the highest betweenness centrality. The top 10 co-cited references revealed the landmark documents that had greatly promoted the development of this field. The major focus is on the cellular and molecular mechanisms of EMT in gliomas, and the therapy related to EMT target and non-coding RNAs has been developing fast in recent years. Conclusions: This study revealed the intimate connections between EMT and gliomas, and the complex mechanisms regulating EMT in gliomas had been studied widely in the last decade. Exploring the deep mechanisms of EMT in gliomas is the foundation of the targeted inhibitions, which can promote the development of therapies for gliomas.
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Background: This study aimed to comprehensively evaluate the toxicity exerted by zinc oxide nanoparticles (ZnO NPs) on rat testis and its effects on fertility and progeny development. Methods: Different concentrations of ZnO NPs were administered by gavage to Sprague Dawley (SD) rats to examine the adverse effects resulting from pre- and post-natal exposure. Systemic distribution of ZnO NPs, developmental performance, sperm parameters, reproductive performance, histopathological examination, and sex hormone levels were determined scheduled in the experimental rats and their male offspring. The comparative in vitro cytotoxicity of the ZnO NPs was determined among C18-4, TM3, and TM4 cells. The toxicity exerted by ZnO NPs on germ cells in vitro and the effects on the expression of cytoskeleton and blood-testis barrier (BTB)-related proteins were also determined. Results: After oral gavage, ZnO NPs mainly accumulated in the liver and testes of rats; 350 mg/kg ZnO NPs adversely affected the epididymal weight, sperm motility, and hormone levels but did not affect the fertility of rats. In addition, 350 mg/kg ZnO NPs significantly reduced the reproductive and developmental performance of offspring male rats. Testicular histopathological and electron microscopic ultrastructure examinations showed more significant abnormal structural changes than those observed in parental rats. The results of in vitro cell experiments further showed that ZnO NPs exerted cytotoxic effects on germ cells, and led to DNA damage, nucleoskeleton and cytoskeleton alterations, and could regulate actin changes through changes in LC3B. Conclusions: It is possible that ZnO NPs act directly on TM4 cells by penetrating the BTB, causing damage to the cytoskeleton and disrupting the dynamic balance of the BTB, thereby destroying the microenvironment necessary for spermatogenesis, which may lead to poor reproduction in rats.