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INTRODUCTION: Despite the widespread provision of free contraceptives and post-abortion care (PAC) services, China grapples with a high rate of unintended pregnancies and subsequent abortions. We aimed to study the evolving characteristics of women seeking abortion and their contraceptive practices before and after abortions, to shed light on the optimisation of Chinese PAC services. METHODS: This study utilised data from an abortion cohort between 2019 and 2021. We studied their demographic features, contraception and abortion histories, reasons and choices using chi-square or linear-by-linear tests. We also explored the potential impact of receiving services at PAC facilities on post-abortion contraception use and repeat abortions using logistic regression models. RESULTS: Among the 9005 participants, 43.4% experienced repeat abortion, without a discernible trend over the 3 years. Noteworthy increases were observed in the percentages of college students (from 1.7% to 6.6%, p<0.01) and middle-aged women (from 23.2% to 26.8%, p<0.01) seeking abortions. Surgical abortion was chosen by nearly 90% of participants with a continuously increasing trend (p trend <0.01). Nearly half of the participants experienced unintended pregnancies due to non-use of contraception. Of the remainder, the majority preferred less or the least effective methods both before and after abortion. Women residing in moderate-gross domestic product (GDP) regions faced a higher risk of repeat abortions (OR 1.33, 95% CI 1.16 to 1.54). Despite this, high-quality PAC services may encourage the use of reliable contraceptive methods, with 86.8% of women changing from least effective or no methods to (most) effective methods post-abortion, and prevent repeat abortions (OR 0.65, 95% CI 0.56 to 0.75). CONCLUSIONS: Increased proportions of college students and middle-aged multiparous women seeking abortions were observed, together with inappropriate preferences for less effective contraception and increasing choice of surgical abortions. Future research should extend the focus to cover the entire abortion period, advocate the rational selection of contraceptive methods, and emphasise the specified PAC services tailored to different socioeconomic groups.
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Mounting evidence has shown that the gut microbiota plays a key role in human health. The homeostasis of the gut microbiota could be affected by many factors, including environmental chemicals. Aldicarb is a carbamate insecticide used to control a variety of insects and nematode pests in agriculture. Aldicarb is highly toxic and its wide existence has become a global public health concern. In our previous study, we have demonstrated that aldicarb disturbed the gut microbial community structure and composition. However, the impacts of aldicarb on gut microbiota-derived metabolites, bile acids, remain elusive. In present study, we performed targeted metabolomics analysis to explore the effects of aldicarb exposure on bile acids, as well as steroid hormones and oxylipins in the serum, feces and liver of C57BL/6â¯J mice. Our results showed that aldicarb exposure disturbed the level of various bile acids, steroid hormones and oxylipins in the serum and feces of C57BL/6â¯J mice. In the liver, the level of cortisol was decreased, meanwhile 15,16-dihydroxyoctadeca-9,12-dienoic acid was increased in aldicarb-treated mice. Metagenomic sequencing analysis showed that the relative abundance of a bile salt hydrolase, choloylglycine hydrolase (EC:3.5.1.24) and a sulfatase enzyme involved in steroid hormone metabolism, arylsulfatase, was significantly increased by aldicarb exposure. Furthermore, correlations were found between gut microbiota and various serum metabolites. The results from this study are helpful to improve the understanding of the impact of carbamate insecticides on host and microbial metabolism.
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Aldicarb , Inseticidas , Humanos , Camundongos , Animais , Ácidos e Sais Biliares , Oxilipinas , Camundongos Endogâmicos C57BL , Hormônios , HomeostaseRESUMO
The wide spread of microplastics has fueled growing public health concern globally. Due to their porous structure and large surface area, microplastics can serve as carriers for other environmental pollutants, including heavy metals. Although the toxic effects of microplastics or heavy metals have been reported previously, investigations into the sex-differential health effects of combined exposure to microplastics and heavy metals are lacking. In the present study, the effects of polystyrene microplastics and lead(II) co-exposure on the gut microbiome, intestinal permeability, and fecal metabolome were examined in both male and female mice. Combined exposure of polystyrene microplastics and lead(II) increased intestinal permeability in both male and female mice. Sex-specific responses to the co-exposure were found in gut bacteria, fungi, microbial metabolic pathways, microbial genes encoding antibiotic resistance and virulence factors, as well as fecal metabolic profiles. In particular, Shannon and Simpson indices of gut bacteria were reduced by the co-exposure only in female mice. A total of 34 and 13 fecal metabolites were altered in the co-exposure group in female and male mice, respectively, among which only three metabolites were shared by both sexes. These sex-specific responses to the co-exposure need to be taken into consideration when investigating the combined toxic effects of microplastics and heavy metals on the gut microbiota.
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Articular cartilage defects pose a significant challenge due to the limited self-healing ability of cartilage. However, traditional techniques face limitations including autologous chondrocyte expansion issues. This study aims to investigate the effects of the polylactic acid-glycolic acid (PLGA) and collagen-surface modified polylactic acid-glycolic acid (CPLGA) microspheres loaded with tetramethylpyrazine (TMP) on two cell types and the regeneration potential of articular cartilage. CPLGA microspheres are prepared by Steglich reaction and characterized. They evaluated the effect of TMP-loaded microspheres on HUVECs (Human Umbilical Vein Endothelial Cells) and examined the compatibility of blank microspheres with BMSCs (Bone marrow mesenchymal stromal cells) and their potential to promote cartilage differentiation. Subcutaneous implant immune tests and cartilage defect treatment are conducted to assess biocompatibility and cartilage repair potential. The results highlight the efficacy of CPLGA microspheres in promoting tissue regeneration, attributed to improved hydrophilicity and collagen-induced mitigation of degradation. Under hypoxic conditions, both CPLGA and PLGA TMP-loaded microspheres exhibit inhibitory effects on HUVEC proliferation, migration, and angiogenesis. Notably, CPLGA microspheres show enhanced compatibility with BMSCs, facilitating chondrogenic differentiation. Moreover, the CPLGA microsphere-composite hydrogel exhibits potential for cartilage repair by modulating angiogenesis and promoting BMSC differentiation.
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Cartilagem Articular , Colágeno , Células Endoteliais da Veia Umbilical Humana , Hidrogéis , Microesferas , Pirazinas , Humanos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Pirazinas/química , Pirazinas/farmacologia , Animais , Colágeno/química , Colágeno/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Condrogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
Background: In the environment of cartilage injury, the activation of vascular endothelial cell (VEC), marked with excessive CD62E and reactive oxygen species (ROS), can affect the formation of hyaluronic cartilage. Therefore, we developed a CD62E- and ROS-responsive drug delivery system using E-selectin binding peptide, Thioketal, and silk fibroin (ETS) to achieve targeted delivery and controlled release of Clematis triterpenoid saponins (CS) against activated VEC, and thus promote cartilage regeneration. Methods: We prepared and characterized ETS/CS and verified their CD62E- and ROS-responsive properties in vitro. We investigated the effect and underlying mechanism of ETS/CS on inhibiting VEC activation and promoting chondrogenic differentiation of bone marrow stromal cells (BMSCs). We also analyzed the effect of ETS/CS on suppressing the activated VEC-macrophage inflammatory cascade in vitro. Additionally, we constructed a rat knee cartilage defect model and administered ETS/CS combined with BMSC-containing hydrogels. We detected the cartilage differentiation, the level of VEC activation and macrophage in the new tissue, and synovial tissue. Results: ETS/CS was able to interact with VEC and inhibit VEC activation through the carried CS. Coculture experiments verified ETS/CS promoted chondrogenic differentiation of BMSCs by inhibiting the activated VEC-induced inflammatory cascade of macrophages via OPA1-mediated mitochondrial homeostasis. In the rat knee cartilage defect model, ETS/CS reduced VEC activation, migration, angiogenesis in new tissues, inhibited macrophage infiltration and inflammation, promoted chondrogenic differentiation of BMSCs in the defective areas. Conclusions: CD62E- and ROS-responsive ETS/CS promoted cartilage repair by inhibiting VEC activation and macrophage inflammation and promoting BMSC chondrogenesis. Therefore, it is a promising therapeutic strategy to promote articular cartilage repair.
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Articular cartilage injury is one of the most common diseases in orthopedic clinics. Following an articular cartilage injury, an inability to resist vascular invasion can result in cartilage calcification by newly formed blood vessels. This process ultimately leads to the loss of joint function, significantly impacting the patient's quality of life. As a result, developing anti-angiogenic methods to repair damaged cartilage has become a popular research topic. Despite this, tissue engineering, as an anti-angiogenic strategy in cartilage injury repair, has not yet been adequately investigated. This exhaustive literature review mainly focused on the process and mechanism of vascular invasion in articular cartilage injury repair and summarized the major regulatory factors and signaling pathways affecting angiogenesis in the process of cartilage injury. We aimed to discuss several potential methods for engineering cartilage repair with anti-angiogenic strategies. Three anti-angiogenic tissue engineering methods were identified, including administering angiogenesis inhibitors, applying scaffolds to manage angiogenesis, and utilizing in vitro bioreactors to enhance the therapeutic properties of cultured chondrocytes. The advantages and disadvantages of each strategy were also analyzed. By exploring these anti-angiogenic tissue engineering methods, we hope to provide guidance for researchers in related fields for future research and development in cartilage repair.
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Cartilagem Articular , Qualidade de Vida , Humanos , Imunoterapia , Inibidores da Angiogênese , Calcificação FisiológicaRESUMO
Sucralose has raised concerns regarding its safety and recent studies have demonstrated that sucralose consumption can disrupt the normal gut microbiome and alter metabolic profiles in mice. However, the extent to which this perturbation affects the functional interaction between the microbiota and the host, as well as its potential impact on host health, remains largely unexplored. Here, we aimed to investigate whether chronic sucralose consumption, at levels within the Acceptable Daily Intake (ADI), could disturb key gut microbial functions and lead to adverse health effects in mice. Following six-month sucralose consumption, several bacterial genera associated with bile acid metabolism were decreased, including Lactobacillus and Ruminococcus. Consequently, the richness of secondary bile acid biosynthetic pathway and bacterial bile salt hydrolase gene were decreased in the sucralose-treated gut microbiome. Compared to controls, sucralose-consuming mice exhibited significantly lower ratios of free bile acids and taurine-conjugated bile acids in their livers. Additionally, several farnesoid X receptor (FXR) agonists were decreased in sucralose-treated mice. This reduction in hepatic FXR activation was associated with altered expression of down-stream genes, in the liver. Moreover, the expression of key lipogenic genes was up-regulated in the livers of sucralose-treated mice. Changes in hepatic lipid profiles were also observed, characterized by lower ceramide levels, a decreased PC/PE ratio, and a mildly increase in lipid accumulation. Additionally, sucralose-consumed mice exhibited higher hepatic cholesterol level compared to control mice, with up-regulation of cholesterol efflux genes and down-regulation of genes associated with reverse cholesterol transport. In conclusion, chronic sucralose consumption disrupts FXR signaling activation and perturbs hepatic lipid and cholesterol homeostasis, potentially by diminishing the bile acid metabolic capacity of the gut microbiome. These findings shed light on the complex interplay between sucralose, the gut microbiota, and host metabolism, raising important questions about the safety of its long-term consumption.
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Microbioma Gastrointestinal , Sacarose/análogos & derivados , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Fígado/metabolismo , Homeostase , Colesterol , Ácidos e Sais Biliares/metabolismo , Lipídeos , Camundongos Endogâmicos C57BLRESUMO
Emerging contaminants have been increasingly recognized as critical determinants in global public health outcomes. However, the intricate relationship between these contaminants and glucose metabolism remains to be fully elucidated. The paucity of comprehensive clinical data, coupled with the need for in-depth mechanistic investigations, underscores the urgency to decipher the precise molecular and cellular pathways through which these contaminants potentially mediate the initiation and progression of diabetes mellitus. A profound understanding of the epidemiological impact of these emerging contaminants, as well as the elucidation of the underlying mechanistic pathways, is indispensable for the formulation of evidence-based policy and preventive interventions. This review systematically aggregates contemporary findings from epidemiological investigations and delves into the mechanistic correlates that tether exposure to emerging contaminants, including endocrine disruptors, perfluorinated compounds, microplastics, and antibiotics, to glycemic dysregulation. A nuanced exploration is undertaken focusing on potential dietary sources and the consequential role of the gut microbiome in their toxic effects. This review endeavors to provide a foundational reference for future investigations into the complex interplay between emerging contaminants and diabetes mellitus.
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Plants, anchored throughout their life cycles, face a unique set of challenges from fluctuating environments and pathogenic assaults. Central to their adaptative mechanisms are transcription factors (TFs), particularly the AP2/ERF superfamily-one of the most extensive TF families unique to plants. This family plays instrumental roles in orchestrating diverse biological processes ranging from growth and development to secondary metabolism, and notably, responses to both biotic and abiotic stresses. Distinguished by the presence of the signature AP2 domain or its responsiveness to ethylene signals, the AP2/ERF superfamily has become a nexus of research focus, with increasing literature elucidating its multifaceted roles. This review provides a synoptic overview of the latest research advancements on the AP2/ERF family, spanning its taxonomy, structural nuances, prevalence in higher plants, transcriptional and post-transcriptional dynamics, and the intricate interplay in DNA-binding and target gene regulation. Special attention is accorded to the ethylene response factor B3 subgroup protein Pti5 and its role in stress response, with speculative insights into its functionalities and interaction matrix in tomatoes. The overarching goal is to pave the way for harnessing these TFs in the realms of plant genetic enhancement and novel germplasm development.
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AIMS: To identify an effective strategy for promoting microvascular endothelial cells (MECs) to phagocytize myelin debris and reduce secretion of inflammatory factors following spinal cord injury (SCI). METHODS: We established a coculture model of myelin debris and vascular-like structures. The efficiency with which MECs phagocytize myelin debris under different conditions was examined via ELISA, flow cytometry, and immunofluorescence. Tubastatin-A was used to interfere with the coculture model. The anti-inflammatory effects of Tubastatin-A were observed by HE staining, flow cytometry, immunofluorescence, and ELISA. RESULTS: MECs phagocytized myelin debris via IgM opsonization, and phagocytosis promoted the secretion of inflammatory factors, whereas IgG-opsonized myelin debris had no effect on inflammatory factors. Application of the HDAC6 inhibitor Tubastatin-A increased the IgG levels and decreased the IgM levels by regulating the proliferation and differentiation of B cells. Tubastatin-A exerted a regulatory effect on the HDAC6-mediated autophagy-lysosome pathway, promoting MECs to phagocytize myelin debris, reducing the secretion of inflammatory factors, and accelerating the repair of SCI. CONCLUSIONS: Inhibition of HDAC6 to regulate the immune-inflammatory response and promote MECs to phagocytize myelin debris may represent a novel strategy in the treatment of SCI.
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Bainha de Mielina , Traumatismos da Medula Espinal , Humanos , Células Endoteliais/metabolismo , Desacetilase 6 de Histona/antagonistas & inibidores , Desacetilase 6 de Histona/metabolismo , Imunoglobulina G/farmacologia , Imunoglobulina M/metabolismo , Macrófagos , Bainha de Mielina/metabolismo , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismoRESUMO
Berries and their functional components have been put forward as an alternative to pharmacological treatments of type 2 diabetes mellitus (T2DM), and more attention has been paid to the gut microbiome in the pathophysiology of T2DM. Thus, we tried to examine the metabolic impact of red bayberry-derived cyanidin-3-O-glucoside (C3G) and investigate whether the antidiabetic effects of C3G were associated with the gut microbiome. As a result, C3G administration was found to reduce blood glucose levels of diabetic db/db mice, accompanied by increased levels of glucagon-like peptide (GLP-1) and insulin. Moreover, 16S rRNA analysis showed that the dominant microbiota modulated by C3G were pivotal in the glucose metabolism. Furthermore, the modulation of C3G on metabolic activities of gut bacteria leads to an increase in intestinal levels of key metabolites, particularly short-chain fatty acids. This contribution helps in promoting the secretion of GLP-1, which in turn increases insulin release with the purpose of reducing blood glucose levels. Overall, these findings may offer new thoughts concerning C3G against metabolic disorders in T2DM.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Insulinas , Camundongos , Animais , Hipoglicemiantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glicemia , Glucosídeos/análise , RNA Ribossômico 16S , Antocianinas/análise , Peptídeo 1 Semelhante ao GlucagonRESUMO
Asthenopia is a syndrome based on the symptoms of eye discomfort that has become a chronic disease that interferes with and harms people's physical and mental health. Lutein is an internationally recognized "eye nutrient", and studies have shown that it can protect the retina and relieve visual fatigue. In this study, lutein was extracted from marigold (Tagetes erecta L.) and saponified. The purified lutein concentration measured by HPLC was 50.12 mg/100 g. Then, purified lutein was modified to be water-soluble by nanoscale modification and microencapsulation technology. Water-soluble lutein was then mixed with a leaching solution of Chinese wolfberry and chrysanthemum to make a functional beverage. The effects of this beverage on hepatic antioxidant enzymes and the alleviation of visual fatigue in a rat model of diabetes were investigated for 4 weeks. Lutein intake of 0.72 (medium-lutein beverage group) and 1.44 mg/mL (high-lutein beverage group) relieved visual fatigue, ameliorated turbidity symptoms of impaired crystalline lenses, reduced hepatic MDA concentration, increased hepatic GSH concentration, and significantly increased the activities of the hepatic antioxidant enzymes SOD, CAT, GSH-Px, and GR in rats. These data suggest that a lutein-rich beverage is an effective and harmless way to increase the total anti-oxidation capacity of lenses and alleviate visual fatigue.
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In order to investigate the potential application of low-grade hard asphalt in high-temperature and high-altitude areas, various tests were conducted to analyze the performance and high-temperature rheological properties of 30#, 50#, and 70# matrix asphalt under thermo-oxidative aging and ultraviolet aging. The tests utilized for analysis included the examination of basic asphalt properties, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), gel permeation chromatography (GPC), dynamic shear rheology (DSR), and multi-stress creep recovery (MSCR). The results indicate a progressive decrease in asphalt performance with increasing aging time. Prolonged exposure to thermal oxygen aging and ultraviolet irradiation significantly diminishes the plasticity of asphalt. The carbonyl index and sulfoxide index of asphalt increase after thermal oxygen aging and ultraviolet aging. Notably, 30# asphalt demonstrates greater resistance to aging compared to 50# and 70# asphalt under long-term high ultraviolet radiation. The LMS% of 30#, 50#, and 70# asphalt increases by 14%, 15%, and 16%, respectively. Following photothermal oxidative aging, a larger proportion of lighter components in the asphalt transforms into resins and asphaltenes. The high-temperature rheological properties of the three types of asphalt rank as 30# > 50# > 70#, while within the same type of asphalt, the high-temperature rheological properties rank as PAV > UV3 > UV2 > UV1 > RTFOT > virgin. Elevating temperature, stress level, and stress duration negatively impact the high-temperature stability of asphalt. In general, low-grade asphalt demonstrates superior anti-aging ability and high-temperature rheological properties during the aging process.
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Iodine deficiency during pregnancy is a widespread public health concern, but indicators and methods for assessing iodine nutritional status are lacking. Serum iodine concentration (SIC) is an important iodine metabolism biomarker and can, to some extent, predict the risk of thyroid diseases, making it a potential biomarker for assessing individual iodine nutrition levels. Our study aimed to analyze the relationship between SIC and thyroid function in a cohort of mild iodine deficient pregnant women in China in order to explore the potential of SIC as a biomarker of individual iodine status in pregnancy. A total of 1540 early pregnant women (gestation < 10 weeks) aged 18 to 45 years old were included in the final study from a Zhejiang multicenter population-based mother and child cohort. Repeated measures of SIC, urinary iodine concentration (UIC), and thyroid function were taken at approximately 10, 17, and 32 weeks of gestation. The SIC was statistically correlated with all thyroid function indexes in the first trimester, and a very strong positive correlation with FT4 over three trimesters (r = 0.449, 0.550, and 0.544, respectively). Pregnant women with an SIC < 72.4 µg/L were at a higher risk of hypothyroxinemia (adjusted OR = 8.911, 95% CI = 5.141-15.447) and iodine deficiency (adjusted OR = 1.244, 95% CI = 1.031-1.502), while those with an SIC > 93.9 µg/L were at a higher risk of thyrotoxicosis (adjusted OR = 11.064, 95% CI = 6.324-19.357) and excessive iodine (adjusted OR = 11.064, 95% CI = 6.324-19.357). In contrast, the UIC was not correlated with thyroid diseases (p > 0.05). These findings indicate that the SIC is a potential biomarker for assessing individual iodine nutrition and thyroid dysfunction in pregnant women.
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Iodo , Desnutrição , Gravidez , Criança , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Gestantes , Estudos de Coortes , China/epidemiologia , BiomarcadoresRESUMO
BACKGROUND: Immune inflammatory responses play an important role in spinal cord injury (SCI); however, the beneficial and detrimental effects remain controversial. Many studies have described the role of neutrophils, macrophages, and T lymphocytes in immune inflammatory responses after SCI, although little is known about the role of B lymphocytes, and immunosuppression can easily occur after SCI. METHODS: A mouse model of SCI was established, and HE staining and Nissl staining were performed to observe the pathological changes. The size and morphology of the spleen were examined, and the effects of SCI on spleen function and B cell levels were detected by flow cytometry and ELISA. To explore the specific mechanism of immunosuppression after SCI, B cells from the spleens of SCI model mice were isolated using magnetic beads and analyzed by 4D label-free quantitative proteomics. The level of inflammatory cytokines and iron ions were measured, and the expression of proteins related to the Tom20 pathway was quantified by western blotting. To clarify the relationship between iron ions and B cell pyroptosis after SCI, we used FeSO4 and CCCP, which induce oxidative stress to stimulate SCI, to interfere with B cell processes. siRNA transfection to knock down Tom20 (Tom20-KD) in B cells and human B lymphocytoma cell was used to verify the key role of Tom20. To further explore the effect of iron ions on SCI, we used deferoxamine (DFO) and iron dextran (ID) to interfere with SCI processes in mice. The level of iron ions in splenic B cells and the expression of proteins related to the Tom20-Bax-caspase-gasdermin E (GSDME) pathway were analyzed. RESULTS: SCI could damage spleen function and lead to a decrease in B cell levels; SCI upregulated the expression of Tom20 protein in the mitochondria of B cells; SCI could regulate the concentration of iron ions and activate the Tom20-Bax-caspase-GSDME pathway to induce B cell pyroptosis. Iron ions aggravated CCCP-induced B cell pyroptosis and human B lymphocytoma pyroptosis by activating the Tom20-Bax-caspase-GSDME pathway. DFO could reduce inflammation and promote repair after SCI by inhibiting Tom20-Bax-caspase-GSDME-induced B cell pyroptosis. CONCLUSIONS: Iron overload activates the Tom20-Bax-caspase-GSDME pathway after SCI, induces B cell pyroptosis, promotes inflammation, and aggravates the changes caused by SCI. This may represent a novel mechanism through which the immune inflammatory response is induced after SCI and may provide a new key target for the treatment of SCI.
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Pseudolinfoma , Traumatismos da Medula Espinal , Animais , Humanos , Camundongos , Linfócitos B , Proteína X Associada a bcl-2 , Carbonil Cianeto m-Clorofenil Hidrazona , Caspases , Gasderminas , Inflamação/etiologia , Ferro , PiroptoseRESUMO
Dietary modulation of the gut microbiota has recently received considerable attention. It is well established that consumption of berries confers a number of health benefits. We previously reported that a black raspberry (BRB)-rich diet effectively modulates the gut microbiota. Given the role of anthocyanins in the health benefits of berries, coupled with interactions of gut microbial metabolites with host health, the objective of this follow-up study was to further characterize the profile of functional metabolites in the gut microbiome modulated by anthocyanins. We utilized a berry-derived classic anthocyanin, cyanidin-3-glucoside (C3G), combined with a mouse model to probe C3G-associated functional metabolic products of gut bacteria through a mass spectrometry-based metabolomic profiling technique. Results showed that C3G substantially changed the gut microbiota of mice, including its composition and metabolic profile. A distinct metabolic profile in addition to a variety of key microbiota-related metabolites was observed in C3G-treated mice. Microbial metabolites involved in protein digestion and absorption were differently abundant between C3G-treated and control mice, which may be linked to the effects of berry consumption. Results of the present study suggest the involvement of the gut microbiota in the health benefits of C3G, providing evidence connecting the gut microbiota with berry consumption and its beneficial effects.
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Perturbations of the gut microbiome are often intertwined with the onset and development of diverse metabolic diseases. It has been suggested that gut microbiome perturbation could be a potential mechanism through which environmental chemical exposure induces or exacerbates human diseases. Microplastic pollution, an emerging environmental issue, has received ever increasing attention in recent years. However, interactions between microplastic exposure and the gut microbiota remain elusive. This study aimed to decipher the responses of the gut microbiome upon microplastic polystyrene (MP) exposure by integrating 16S rRNA high-throughput sequencing with metabolomic profiling techniques using a C57BL/6 mouse model. The results indicated that MP exposure significantly perturbed aspects of the gut microbiota, including its composition, diversity, and functional pathways that are involved in xenobiotic metabolism. A distinct metabolite profile was observed in mice with MP exposure, which probably resulted from changes in gut bacterial composition. Specifically, untargeted metabolomics revealed that levels of metabolites associated with cholesterol metabolism, primary and secondary bile acid biosynthesis, and taurine and hypotaurine metabolism were changed significantly. Targeted approaches indicated significant perturbation with respect to the levels of short-chain fatty acids derived from the gut microbiota. This study can provide evidence for the missing link in understanding the mechanisms behind the toxic effects of microplastics.
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CONTEXT: Wen-Shen-Tong-Luo-Zhi-Tong (WSTLZT) Decoction is a Chinese prescription with antiosteoporosis effects, especially in patients with abnormal lipid metabolism. OBJECTIVE: To explore the effect and mechanism of WSTLZT on osteoporosis (OP) through adipocyte-derived exosomes. MATERIALS AND METHODS: Adipocyte-derived exosomes with or without WSTLZT treated were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blotting (WB). Co-culture experiments for bone marrow mesenchymal stem cells (BMSCs) and exosomes were performed to examine the uptake and effect of exosome in osteogenesis and adipogenic differentiation of BMSC. MicroRNA profiles, luciferase and IP were used for exploring specific mechanisms of exosome on BMSC. In vivo, 80 Balb/c mice were randomly divided into four groups: Sham, Ovx, Exo (30 µg exosomes), Exo-WSTLZT (30 µg WSTLZT-exosomes), tail vein injection every week. After 12 weeks, the bone microstructure and marrow fat distribution were analysed by micro-CT. RESULTS: ALP, Alizarin red and Oil red staining showed that WSTLZT-induced exosomes from adipocyte can regulate osteoblastic and adipogenic differentiation of BMSC. MicroRNA profiles observed that WSTLZT treatment resulted in 87 differentially expressed miRNAs (p < 0.05). MiR-122-5p with the greatest difference was screened by q-PCR (p < 0.01). The target relationship between miR-122-5p and SPRY2 was tested by luciferase and IP. MiR-122-5p negatively regulated SPRY2 and elevated the activity of MAPK signalling pathway, thereby regulating the osteoblastic and adipogenic differentiation of BMSC. In vivo, exosomes can not only improve bone microarchitecture but also significantly reduce accumulation of bone marrow adipose. CONCLUSIONS: WSTLZT can exert anti-OP effect through SPRY2 via the MAKP signalling by miR-122-5p carried by adipocyte-derived exosomes.
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Exossomos , MicroRNAs , Camundongos , Animais , Exossomos/genética , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular , Adipogenia , Osteogênese , AdipócitosRESUMO
Mounting evidence has linked berries to a variety of health benefits. We previously reported that administration of a diet rich in black raspberries (BRBs) impacted arsenic (As) biotransformation and reduced As-induced oxidative stress. To further characterize the role of the gut microbiota in BRB-mediated As toxicity, we utilized the dietary intervention of BRBs combined with a mouse model to demonstrate microbial changes by examining associated alterations in the gut microbiota, especially its functional metabolites. Results showed that BRB consumption changed As-induced gut microbial alterations through restoring and modifying the gut microbiome, including its composition, functions and metabolites. A number of functional metabolites in addition to bacterial genera were significantly altered, which may be linked to the effects of BRBs on arsenic exposure. Results of the present study suggest functional interactions between dietary administration of black raspberries and As exposure through the lens of the gut microbiota, and modulation of the gut microbiota and its functional metabolites could contribute to effects of administration of BRBs on As toxicity.
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Perfluorooctanoic acid is a manufactured material extensively utilized in industrial and consumer products. As a persistent organic pollutant, perfluorooctanoic acid has raised increasing public health concerns recently. Although perfluorooctanoic acid is known to induce lipid accumulation in the liver, the impact of perfluorooctanoic acid on different lipid classes has not been fully evaluated. In this study, we performed untargeted lipidomics analysis to investigate the impact of perfluorooctanoic acid on the lipid homeostasis in C57BL/6 male mice. Perfluorooctanoic acid disturbed the lipid profiles in serum and liver, with a variety of lipid classes significantly altered. Greater impacts were observed in the liver lipidome than the serum lipidome. In particular, some lipid clusters in the liver were altered by both high- and low-dose perfluorooctanoic acid exposure, including the increase of unsaturated triglycerides and the decrease of sphingomyelins, saturated phosphatidylcholines, saturated lysophosphatidylcholines, and phospholipid ethers. In parallel with an increase in the liver, a decrease of saturated phosphatidylcholines was found in the serum of high-dose perfluorooctanoic acid-treated mice. The findings from this study are helpful to improve the understanding of perfluorooctanoic acid-induced dysregulation of lipid metabolism and perfluorooctanoic acid-associated health effects in liver.