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Reovirus (Reo) has shown promising potential in specifically killing tumor cells, and offering new possibilities for ovarian cancer (OC) treatment. However, neutralizing antibodies in the ascites from OC patients greatly limit the further application of Reo. In this study, we employed cationic liposomes (Lipo) to deliver Reo, significantly enhancing its ability to enter OC cells and its effectiveness in killing these cells under ascitic conditions. Pre-treatment with the MßCD inhibitor notably decreased Reo-mediated tumor cell death, indicating that Lipo primarily enables Reo's cellular uptake through caveolin-mediated endocytosis. Our results demonstrate that Lipo effectively facilitates the entry of Reo into the cytoplasm and triggers cell apoptosis. The above findings provide a new strategy to overcome the obstacle of neutralizing antibodies in the clinical application of Reo.
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Anticuerpos Neutralizantes , Liposomas , Neoplasias Ováricas , Reoviridae , Femenino , Humanos , Neoplasias Ováricas/inmunología , Anticuerpos Neutralizantes/inmunología , Reoviridae/inmunología , Reoviridae/fisiología , Línea Celular Tumoral , Viroterapia Oncolítica/métodos , Apoptosis , Animales , Cationes , Virus Oncolíticos/inmunología , RatonesRESUMEN
AIM: Angiogenesis is a key event in the successful healing of pulp injuries, and hypoxia is the main stimulator of pulpal angiogenesis. In this study, we investigated the effect of hypoxia on the proangiogenic potential of human dental pulp stem cells (hDPSCs) and the role of miR-143-5p in the process. METHODOLOGY: Human dental pulp stem cells were isolated, cultured and characterized in vitro. Cobalt chloride (CoCl2) was used to induce hypoxia in hDPSCs. CCK-8 and Transwell assays were used to determine the effect of hypoxia on hDPSCs proliferation and migration. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB) and ELISA were performed to assess the mRNA and protein levels of HIF-1α and angiogenic cytokines in hDPSCs. The effect of hypoxia on hDPSCs proangiogenic potential was measured in vitro using Matrigel tube formation and chick chorioallantoic membrane (CAM) assays. Recombinant lentiviral vectors were constructed to stably overexpress or inhibit miR-143-5p in hDPSCs, and the proangiogenic effects were assessed using qRT-PCR, WB, and tube formation assays. miR-143-5p target genes were identified and verified using bioinformatics prediction tools, dual-luciferase reporter assays and RNA pull-down experiments. Finally, a subcutaneous transplantation model in nude mice was used to determine the effects of hypoxia treatment and miR-143-5p overexpression/inhibition in hDPSCs in dental pulp regeneration. RESULTS: Hypoxia promotes hDPSCs proliferation, migration and proangiogenic potential. The in vivo experiments showed that hypoxia treatment (50 and 100 µM CoCl2) promoted pulp angiogenesis and dentine formation. In contrast to the levels of proangiogenic factors, miR-143-5p levels decreased with increasing CoCl2 concentration. miR-143-5p inhibition significantly promoted proangiogenic potential of hDPSCs, whereas miR-143-5p overexpression inhibited angiogenesis in vitro. Dual-luciferase reporter assay identified retinoic acid receptor-related orphan receptor alpha (RORA) as an miR-143-5p target gene in hDPSCs. RNA pull-down experiments demonstrated that HIF-1α and RORA were pulled down by biotin-labelled miR-143-5p, and the levels of HIF-1α and RORA bound to miR-143-5p in the hypoxia group were lower than those in the normoxia group. Inhibition of miR-143-5p expression in hDPSCs promoted ectopic dental pulp tissue regeneration. CONCLUSIONS: CoCl2-induced hypoxia promotes hDPSCs-driven paracrine angiogenesis and pulp regeneration. The inhibition of miR-143-5p upregulates the proangiogenic potential of hDPSCs under hypoxic conditions by directly targeting HIF-1α and RORA.
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The conversion of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes represents a significant epigenetic modification, yet its role in early human embryos remains largely unknown. Here we showed that the early human embryo inherited a significant amount of 5hmCs from an oocyte, which unexpectedly underwent de novo hydroxymethylation during its growth. Furthermore, the generation of 5hmC in the paternal genome after fertilization roughly followed the maternal pattern, which was linked to DNA methylation dynamics and regions of sustained methylation. The 5hmCs persisted until the eight-cell stage and exhibited high enrichment at OTX2 binding sites, whereas knockdown of OTX2 in human embryos compromised the expression of early lineage genes. Specifically, the depletion of 5hmC affected the activation of embryonic genes, which was further evaluated by ectopically expressing mouse Tet3 in human early embryos. These findings revealed distinct dynamics of 5hmC and unravelled its multifaceted functions in early human embryonic development.
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Background: Previous studies have shown that serotonin and its receptors are widely distributed in mammalian reproductive tisssues and play an important role in embryonic development. However, the specific effects of the serotonergic system on embryonic arrest (EA) and the underlying mechanism require further investigation. Methods: Chorionic villi were collected from patients with EA and healthy pregnant women. Western blotting (WB) and immunohistochemistry (IHC) were used to detect serotonin receptor 1B (HTR1B) levels and evaluate mitochondrial function. Additionally, HTR-8/SVneo cells were transfected with an HTR1B overexpression plasmid. Quantitative real-time polymerase chain reaction(qRT-PCR), Cell Counting Kit-8 (CCK-8), and wound healing assays were utilized to evaluate mitophagy level, cell proliferation and cell migration, respectively. Results: We discovered elevated HTR1B levels in the chorionic villi of the patients with EA compared to controls. Concurrently, we observed enhanced levels of nucleus-encoded proteins including mitofilin, succinate dehydrogenase complex subunit A (SDHA), and cytochrome c oxidase subunit 4 (COXIV), along with the mitochondrial fusion protein optic atrophy 1(OPA1), fission proteins mitochondrial fission protein 1(FIS1) and mitochondrial fission factor (MFF) in the EA group. Additionally, there was an excessive mitophagy levels in EA group. Furthermore, a notable activation of mitogen-activated protein kinase (MAPK) signaling pathway proteins including extracellular regulating kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 was observed in the EA group. By overexpressing HTR1B in HTR-8/SVneo cells, we observed a significant reduction in cell proliferation and migration. HTR1B overexpression also caused an increase in levels of SDHA and FIS1, as well as an upregulation of mitophagy. Notably, the ERK inhibitor U0126 effectively mitigated these effects. Conclusion: These findings show that HTR1B influences mitochondrial homeostasis, promoting excessive mitophagy and impairing cell proliferation and migration by activating the MAPK signalling pathway during post-implantation EA. Therefore, HTR1B may serve as a potential therapeutic target for patients with EA.
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Stress is an emotional state caused by an unexpected external environmental change or stimulus, and several experiments have demonstrated its negative impact on ovarian function, ultimately affecting reproductive ability. Melatonin (MT) has been shown to facilitate oocyte maturation and enhance ovarian function by regulating mitochondrial function. However, the specific effect and underlying molecular mechanisms of MT on stress-induced ovarian dysfunction remain largely unknown. In this study, we established a mouse model of chronic unpredictable mild stress (CUMS) to investigate its impact on ovarian function. Our findings revealed that CUMS led to premature ovarian insufficiency (POI) in mice, characterized by a reduction in follicle numbers and decreased levels of anti-Müllerian hormone (AMH) and bone morphogenetic protein 15 (BMP15). Furthermore, CUMS caused decreased expression of mitochondrial fission protein 1 (FIS1) and enhanced level of mitochondrial fusion protein optic atrophy 1(OPA1), mitofusin1(MFN1), as well as nucleus-encoded protein succinate dehydrogenase complex A (SDHA), reflecting mitochondrial dyshomeostasis. Additionally, CUMS resulted in excessive autophagy and apoptosis. However, MT reversed these effects and improved ovarian damage. Importantly, the protective effects of MT were mediated through the inhibition of the eIF2α-AFT4 pathway. Overall, this study provides valuable insights into the treatment of POI caused by CUMS.
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OBJECTIVE: Recent studies have indicated that HOTTIP and MEG3 are associated with the initiation and progression of various types of tumors, including nasopharyngeal carcinoma (NPC). This investigation aimed to elucidate the impact of HOTTIP and MEG3 polymorphisms on the susceptibility and clinicopathologic characteristics of NPC. METHODS: This research employed next-generation sequencing and multiplex PCR to assess the polymorphisms of HOTTIP rs1859168 and MEG3 rs7158663 in 200 NPC and 200 healthy individuals respectively. HOTTIP and MEG3 expression were assessed via qRT-PCR assessment. Furthermore, the genotypes and alleles frequency of rs1859168 and rs7158663 were compared between healthy and NPC individuals to elucidate their influence on NPC susceptibility and relation with clinicopathologic characteristics. RESULTS: In comparison with the healthy cohort, the presence of HOTTIP rs1859168 CC genotype and the C allele were markedly linked with increased NPC incidence (p < 0.05). Furthermore, the MEG3 rs7158663 AA genotype and the A allele also indicated an increased risk of NPC (p < 0.05). The subgroup analysis of age, EBV infection, gender, nationality, smoking, and drinking status revealed no marked association between rs1859168 and rs7158663 genotypes and these potential confounding factors. Moreover, it was observed that rs1859168 CC and rs7158663 AA genotypes were related to local tumor invasion and lymph node metastasis. Additionally, HOTTIP indicated a marked elevation, while MEG3 substantially reduced in NPC samples than the normal nasopharyngeal biospecimens. Patients who carried CC or CA genotypes rather than the HOTTIP rs1859168 AA genotype, had substantially higher HOTTIP levels, while patients with rs7158663 AA or GA genotypes indicated notably lower expression of MEG3 than GG genotype carriers. CONCLUSION: Individuals with genetic variants of HOTTIP rs1859168 and MEG3 rs7158663 might have an increased risk of NPC susceptibility and related clinicopathologic characteristics, potentially by affecting the expression of HOTTIP and MEG3.
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Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess anti-inflammatory and antioxidative effects in various neurodegenerative diseases. However, its specific effects on retinitis pigmentosa (RP) have not been thoroughly investigated. Therefore, the objective of this study was to explore the potential role of minocycline in treating RP. In this investigation, we used rd1 to explore the antioxidant effect of minocycline in RP. Minocycline therapy effectively restored retinal function and structure in rd1 mice at 14 days postnatal. Additionally, minocycline inhibited the activation of microglia. Moreover, RNA sequencing analysis revealed a significant downregulation in the expression of mitochondrial genes within the retina of rd1 mice. Further KEGG and GO pathway analysis indicated impaired oxidative phosphorylation and electron transport chain processes. TEM confirmed the presence of damaged mitochondria in photoreceptors, while JC-1 staining demonstrated a decrease in mitochondrial membrane potential, accompanied by an increase in mitochondrial reactive oxygen species (ROS) levels. However, treatment with minocycline successfully reversed the abnormal expression of mitochondrial genes and reduced the levels of mitochondrial ROS, thereby providing protection against photoreceptor degeneration. Collectively, minocycline demonstrated the ability to rescue photoreceptor cells in RP by effectively modulating mitochondrial homeostasis and subsequently inflammation. These findings hold significant implications for the development of potential therapeutic strategies for RP.
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Homeostasis , Minociclina , Mitocondrias , Especies Reactivas de Oxígeno , Retinitis Pigmentosa , Minociclina/farmacología , Minociclina/uso terapéutico , Animales , Retinitis Pigmentosa/tratamiento farmacológico , Retinitis Pigmentosa/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Homeostasis/efectos de los fármacos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Degeneración Retiniana/tratamiento farmacológico , Degeneración Retiniana/patología , Degeneración Retiniana/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Células Fotorreceptoras de Vertebrados/patología , Células Fotorreceptoras de Vertebrados/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microglía/efectos de los fármacos , Microglía/metabolismo , Retina/efectos de los fármacos , Retina/patología , Retina/metabolismo , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéuticoRESUMEN
Male infertility is a major concern affecting reproductive health. Biallelic deleterious variants of most DNAH gene family members have been linked to male infertility, with intracytoplasmic sperm injection (ICSI) being an efficacious way to achieve offspring. However, the association between DNAH12 and male infertility is still limited. Here, we identified one homozygous variant and two compound heterozygous variants in DNAH12 from three infertile Chinese men. Semen analysis revealed severe asthenozoospermia, abnormal morphology, and structure of sperm flagella. Furthermore, the Dnah12 knock-out mouse revealed severe spermatogenesis failure and validated the same male infertility phenotype. Favorable fertility outcomes were achieved through ICSI in three human individuals and Dnah12 knock-out mice. Collectively, our study indicated that biallelic variants of DNAH12 can induce male infertility in both human beings and mice. Notably, evidence from DNAH12 enhanced that ICSI was an optimal intervention to achieve favorable fertility outcomes for infertile males with DNAH gene family variants.
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In this paper, we present a new type of isolator based on one-way surface magnetoplasmons (SMPs) at microwave frequencies, and it is the first time that an experimental prototype of isolator with wideband and ultra-high isolation is realized using SMP waveguide. The proposed model with gyromagnetic and dielectric layers is systematically analyzed to obtain the dispersion properties of all the possible modes, and a one-way SMP mode is found to have the unidirectional transmission property. In simulation and experiment with metallic waveguide loaded with yttrium-iron-garnet (YIG) ferrite, the scattering parameters and the field distributions agree well with the analysis and verify the one-way transmission property. The isolation is found to be as high as 80 dB and the typical value of insertion loss is 1 dB. Besides, the one-way transmission band can be controlled by changing the magnetic bias. From theoretical analysis and simulation, it is found that with a tiny value of 10 Oe of the magnetic bias, the relative bandwidth can be tuned to be greater than 50%. Compared with conventional isolators, this one-way SMP isolator has the advantages of ultra-high isolation, wide relative frequency band, and requires much smaller bias field, which has promising potential in non-reciprocal applications.
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Purpose: The impact of delayed diagnosis on tumor-related prognosis appears to be minimal in individuals with intracranial germ cell tumors (iGCTs). However, its effect on neuroendocrine functions remains unclear. We aimed to assess the effects of delayed diagnosis on neuroendocrine function in individuals with suprasellar GCTs. Methods: We conducted a retrospective cohort study of 459 individuals with suprasellar GCTs and categorized them into two groups based on disease duration: delayed diagnosis (> 6 months) and non-delayed diagnosis (≤ 6 months). We compared endocrinological symptoms, neuroendocrine dysfunction and its grading (categorized into 0-3 grades based on severity), and recovery from neuroendocrine dysfunction in both groups. Results: Patients with delayed diagnosis exhibited higher incidences of amenorrhea, slow growth, fatigue, and polyuria/polydipsia. Neuroendocrine dysfunction, including central adrenal insufficiency (CAI), central hypothyroidism (CHT), arginine vasopressin deficiency (AVP-D), growth hormone deficiency, hypogonadism, and hyperprolactinemia, was more pronounced in the delayed diagnosis group at diagnosis, the end of treatment, and the last follow-up. Furthermore, individuals with delayed diagnosis showed higher grades of neuroendocrine dysfunction at diagnosis (OR=3.005, 95% CI 1.929-4.845, p<0.001), end of oncologic treatment (OR=4.802, 95% CI 2.878-8.004, p<0.001), and last follow-up(OR=2.335, 95% CI 1.307-4.170, p=0.005) after adjusting for confounders. Finally, less recovery, particularly in CAI, CHT, and AVP-D, was seen among the group with delayed diagnosis after treatment. Conclusion: Among individuals with suprasellar GCTs, delayed diagnosis is associated with increased, more severe, and less recovered neuroendocrine dysfunction, emphasizing the importance of early diagnosis and treatment to reduce neuroendocrine dysfunction.
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Diagnóstico Tardío , Neoplasias de Células Germinales y Embrionarias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Adulto , Adulto Joven , Adolescente , Pronóstico , Sistemas Neurosecretores/fisiopatología , Persona de Mediana Edad , Estudios de SeguimientoRESUMEN
C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to infection and during chronic inflammatory disorders. Systemic inflammation is a major driver of cirrhosis progression from the compensated to the decompensated stage. Previous studies have shown that pentameric CRP (pCRP) to be a weak predictor of disease severity and prognosis in patients with decompensated hepatitis B cirrhosis, with it being only helpful for identifying patients with a higher short-term risk of death under certain conditions. Accumulating evidence indicates that pCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci, suggesting that mCRP may be a potentially superior disease marker with higher specificity and relevance to pathogenesis. However, it is unknown whether mCRP and anti-mCRP autoantibodies are associated with disease severity, or progression in decompensated hepatitis B cirrhosis. In this study, we evaluated the serum levels of mCRP and anti-mCRP autoantibodies in patients with decompensated cirrhosis of hepatitis B and their association with disease severity and theoretical prognosis. The results showed that patients with high mCRP and anti-mCRP autoantibody levels had more severe liver damage and that coagulation function was worse in patients with high anti-mCRP autoantibodies. Analysis of the correlation between pCRP, mCRP and anti-mCRP autoantibody levels with Model for End-Stage Liver Disease (MELD), Albumin-Bilirubin (ALBI), and Child-Turcotte-Pugh (CTP) prognostic scores showed that mCRP was the most strongly correlated with MELD score, followed by anti-mCRP autoantibodies; conversely, pCRP was not significantly correlated with prognostic score. Therefore, mCRP and anti-mCRP autoantibodies may be more advantageous clinical indicators than pCRP for evaluating the pathological state of decompensated hepatitis B cirrhosis.
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Autoanticuerpos , Biomarcadores , Proteína C-Reactiva , Cirrosis Hepática , Índice de Severidad de la Enfermedad , Humanos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Femenino , Pronóstico , Masculino , Cirrosis Hepática/inmunología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Persona de Mediana Edad , Biomarcadores/sangre , Adulto , Progresión de la Enfermedad , Hepatitis B/inmunología , Hepatitis B/sangreRESUMEN
Mangiferin, a naturally occurring potent glucosylxanthone, is mainly isolated from the Mangifera indica plant and shows potential pharmacological properties, including anti-bacterial, anti-inflammation, and antioxidant in sepsis-induced lung and kidney injury. However, there was a puzzle as to whether mangiferin had a protective effect on sepsis-associated encephalopathy. To answer this question, we established an in vitro cell model of sepsis-associated encephalopathy and investigated the neuroprotective effects of mangiferin in primary cultured hippocampal neurons challenged with lipopolysaccharide (LPS). Neurons treated with 20 µmol/L or 40 µmol/L mangiferin for 48 h can significantly reverse cell injuries induced by LPS treatment, including improved cell viability, decreased inflammatory cytokines secretion, relief of microtubule-associated light chain 3 expression levels and several autophagosomes, as well as attenuated cell apoptosis. Furthermore, mangiferin eliminated pathogenic proteins and elevated neuroprotective factors at both the mRNA and protein levels, showing strong neuroprotective effects of mangiferin, including anti-inflammatory, anti-autophagy, and anti-apoptotic effects on neurons in vitro.
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Apoptosis , Hipocampo , Lipopolisacáridos , Neuronas , Fármacos Neuroprotectores , Xantonas , Xantonas/farmacología , Animales , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Fármacos Neuroprotectores/farmacología , Células Cultivadas , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Autofagia/efectos de los fármacos , Ratas , Citocinas/metabolismoRESUMEN
Polycystic ovary syndrome (PCOS) severely affects women's fertility and accompanies serious metabolic disturbances, affecting 5%-20% of women of reproductive age globally. We previously found that exposure to toxic metals in the blood raised the risk of PCOS, but the association between exposure to toxic metals and the risk of PCOS in the follicular fluid, the microenvironment for oocyte growth and development in females, and its effect on metabolism has not been reported. This study aimed to evaluate the associations between the concentrations of cadmium (Cd), mercury (Hg), barium (Ba) and arsenic (As) in FF and the risk of PCOS, and to explore the mediating effect of metabolic markers in FF on the above relationship. We conducted a case-control study, including 557 women with PCOS and 651 controls. Ba, Cd, Hg and As levels in FF were measured by ICP-MS, metabolites levels in FF was measured by LC-MS/MS among 168 participants randomly selected from all the participants. Logistic regression models were used to assess the association of a single metal level with the PCOS risk, and linear regression models were used to assess the relationships of a single metal level with clinical phenotype parameters and metabolites levels. Combined effect of metals mixture levels on the risk of PCOS were assessed via weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR). Medication analysis was performed to explore the role of metabolic markers on the relationship of toxic metals levels with the risk of PCOS. The exposure levels of Cd, Hg, Ba and As in FF were all positively and significantly associated with the PCOS risk (with respect to the highest vs. lowest tertile group: OR = 1.57, 95% CI = 1.17 ~ 2.12 for Cd, OR = 1.69, 95% CI = 1.22 ~ 2.34 for Hg, OR = 1.76, 95% CI = 1.32 ~ 2.34 for Ba, OR = 1.42, 95% CI = 1.05 ~ 1.91 for As). In addition, levels of metal mixture also significantly correlated with the risk of PCOS, Cd level contributed most to it. Moreover, we observed significant positive relationships between Cd level and LH (ß = 0.048, 95% CI = 0.002 ~ 0.094), T (ß = 0.077, 95% CI = 0.029 ~ 0.125) and HOMA-IR value (ß = 0.060, 95% CI = 0.012 ~ 0.107), as well as Hg level with LH, FSH/LH ratio and TC. Furthermore, we revealed that estrone sulfate, LysoPE 22:6 and N-Undecanoylglycine were significantly and positively mediating the association between Cd level and the risk of PCOS (with mediated proportion of 0.39, 0.24 and 0.35, respectively), and between Hg level and the risk of PCOS (with mediated proportion of 0.29, 0.20 and 0.46, respectively). These highly expressed metabolites significantly enriched in the fatty acid oxidation, steroid hormone biosynthesis and glycerophospholipids metabolism, which may explain the reason why the levels of Cd and Hg in FF associated with the phenotype of PCOS. Ba and As in FF was not found the above phenomenon. Our results suggested that exposure to multiple toxic metals (Cd, Hg, Ba and As) in FF associated with the increased risk of PCOS, Cd was a major contributor. Levels of Cd and Hg in FF significantly associated with the phenotype of PCOS. The above association may result from that Cd and Hg in FF related with the disturbance of fatty acid oxidation, steroid hormone biosynthesis and the glycerophospholipids metabolism.
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OBJECTIVE: The pathogenesis of GDM and T2DM are closely related to various metals in vivo, and changes in the concentration of these metal exposures can lead to neuropathy through the DNA damage pathway caused by the accumulation of ROS. METHOD: Urine samples were analyzed for heavy metals and trace elements by ICP-MS, neurotransmitter metabolites by HPLC, 8-OH-dG by HPLC-MS and metabolomics by UPLC-MS. RESULT: Cd and Hg were risk factors for T2DM. There was a positive correlation between 8-OH-dG and neurotransmitter metabolites in both two populations. For GDM, the metabolite with the largest down-regulation effect was desloratadine and the largest up-regulation effect was D-glycine. That tyrosine and carbon metabolites were upregulated in the GDM population and downregulated in the T2DM population. CONCLUSION: The BMI, urinary Cd and Hg endo-exposure levels correlated with elevated blood glucose, and the latter may cause changes in the DNA damage marker 8-OH-dG in both study populations and trigger common responses to neurological alterations changes in the neurotransmitter. Tyrosine, carbonin metabolites, alanine, aspartate, and glutamate were signature metabolites that were altered in both study populations. These indicators and markers have clinical implications for monitoring and prevention of neurological injury in patients with GDM and T2DM.
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Neurotransmisores , Humanos , Femenino , Neurotransmisores/orina , Neurotransmisores/metabolismo , Adulto , Embarazo , Persona de Mediana Edad , Cadmio/orina , 8-Hidroxi-2'-Desoxicoguanosina/orina , Oligoelementos/orina , Cromatografía Líquida de Alta PresiónRESUMEN
Illicium verum Hook. f. is a globally significant spice, which is recognized in China as a food-medicine homolog and extensively utilized across the pharmaceutical, food, and spice industries. China boasts the world's leading resources of I. verum, yet its comprehensive utilization remains relatively underexplored. Through a resource survey of I. verum and the application of bibliometric visualization using CiteSpace, this study analyzed 324 papers published in the Web of Science Core Collection (WOSCC) from 1962 to 2023 and 353 core documents from China's three major databases (CNKI, Wanfang Database, and VIP Database). I. verum from Guangxi province towards various southern provinces in China, with autumn fruits exhibited superior quality and market value over their spring fruits. Literature in WOSCC emerged earlier, with a research emphasis on food science technology and pharmacology pharmacy domains. WOSCC research on I. verum could be divided into two phases: an embryonic period (1962-2001) and a growth period (2002-2023), showing an overall upward trend in publication. The three major Chinese databases contain a larger number of publications, with a focus on the food sector, which could be categorized into three stages: an embryonic period (1990-1999), a growth period (2000-2010), and a stable period (2011-2023), with an overall downward trend in publication. Both Chinese and international research hotspots converge on the medical applications of I. verum, with antioxidant bioactivity research emerging as a prevailing trend. This study delineated the resource distribution of I. verum across China and identified the research hotspots and trends both in China and internationally. The findings are beneficial for guiding researchers in swiftly establishing their research focus and furnishing decision-makers with a comprehensive reference for industry information.
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An infantile hemangioma is a congenital benign tumor formed by the proliferation of vascular cells during the embryonic stage. It is more common in the skin but can also occur in the mucous membranes, liver, brain and muscle. Hepatic hemangioma appears to be a benign tumor; however, it may lead to poor outcomes because of severe complications, such as high-output cardiac failure. The main treatment of hepatic hemangioma in infants is oral drugs, such as propranolol and glucocorticoids, but the clinical response is not always satisfactory. We describe a rare case of a 2-month-old boy who presented with infantile cutaneous and hepatic hemangiomas. By using dermoscopy and observations of the abdominal color Doppler ultrasound, after 9 months of oral treatment with itraconazole solution, the infantile cutaneous hemangioma complicated with hepatic hemangioma was eventually cured. There was no liver or kidney function damage during the whole treatment period. Itraconazole oral solution for the treatment of infantile cutaneous hemangioma complicated with hepatic hemangioma showed good efficacy, compliance, and safety in this case.
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BACKGROUND: The relationship between the triglyceride-glucose (TyG) index and the risk of cardiovascular disease (CVD) in the U.S. population under 65 years of age with diabetes or prediabetes is unknown. The purpose of this study was to investigate the relationship between baseline TyG index and CVD risk in U.S. patients under 65 years of age with diabetes or prediabetes. METHODS: We used data from the 2003-2018 National Health and Nutrition Examination Survey (NHANES). Multivariate regression analysis models were constructed to explore the relationship between baseline TyG index and CVD risk. Nonlinear correlations were explored using restricted cubic splines. Subgroup analysis and interaction tests were also conducted. RESULTS: The study enrolled a total of 4340 participants with diabetes or pre-diabetes, with a mean TyG index of 9.02 ± 0.02. The overall average prevalence of CVD was 10.38%. Participants in the higher TyG quartiles showed high rates of CVD (Quartile 1: 7.35%; Quartile 2: 10.04%; Quartile 3: 10.71%; Quartile 4: 13.65%). For CVD, a possible association between the TyG index and the risk of CVD was observed. Our findings suggested a linear association between the TyG index and the risk of CVD. The results revealed a U-shaped relationship between the TyG index and both the risk of CVD (P nonlinear = 0.02583) and CHF (P nonlinear = 0.0208) in individuals with diabetes. Subgroup analysis and the interaction term indicated that there was no significant difference among different stratifications. Our study also revealed a positive association between the TyG index and comorbid MetS in the U.S. population under 65 years of age with prediabetes or diabetes. CONCLUSIONS: A higher TyG index was linked to an increased likelihood of CVD in the U.S. population aged ≤ 65 years with prediabetes and diabetes. Besides, TyG index assessment will contribute to more convenient and effective screening of high-risk individuals in patients with MetS. Future studies should explore whether interventions targeting the TyG index may improve clinical outcomes in these patients.
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Biomarcadores , Glucemia , Enfermedades Cardiovasculares , Diabetes Mellitus , Encuestas Nutricionales , Estado Prediabético , Triglicéridos , Humanos , Estado Prediabético/sangre , Estado Prediabético/epidemiología , Estado Prediabético/diagnóstico , Femenino , Masculino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/sangre , Estados Unidos/epidemiología , Persona de Mediana Edad , Glucemia/metabolismo , Medición de Riesgo , Triglicéridos/sangre , Biomarcadores/sangre , Diabetes Mellitus/epidemiología , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Prevalencia , Adulto , Estudios Transversales , Factores de Riesgo de Enfermedad Cardiaca , Pronóstico , Factores de Edad , Factores de Riesgo , Valor Predictivo de las PruebasRESUMEN
The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.
Asunto(s)
Estudio de Asociación del Genoma Completo , Cabeza , Neoplasias , Humanos , Cabeza/anatomía & histología , Neoplasias/genética , Neoplasias/patología , Femenino , Masculino , Polimorfismo de Nucleótido Simple/genética , Variación Genética , Tamaño de los Órganos/genética , Transducción de Señal/genética , Adulto , Predisposición Genética a la EnfermedadRESUMEN
BACKGROUND AND AIM: The impact of trace elements and heavy metals on human health has attracted widespread attention. However, the correlation between urinary chromium concentrations and blood pressure remains unclear and inadequately reported, and the aim of this study was to investigate the relationship between urinary chromium concentrations and blood pressure in adults in the United States (US). METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 for this study. Multivariate logistic regression and multivariate linear regression were used to explore the association of urinary chromium concentrations with hypertension and blood pressure. Additionally, we also performed subgroup analysis and restricted cubic splines (RCS). RESULTS: A total of 2958 participants were enrolled in this study. The overall mean systolic blood pressure and diastolic blood pressure were 123.98 ± 0.60, 72.66 ± 0.57 mmHg, respectively. The prevalence of hypertension was found in 41.31% of the whole participants. In the fully adjusted model, we did not observe a correlation between urinary chromium concentrations and the risk of hypertension and systolic blood pressure. However, we found a negative association between urinary chromium concentrations and diastolic blood pressure. In subgroup analysis, we observed a positive association between urinary chromium and the risk of hypertension among participants older than 60 years of age and those who were Non-Hispanic Black. The interaction term highlighted the influence of age and race on this positive association. We also found a negative association of urinary chromium with diastolic blood pressure in male, participants who were current smokers, overweight, and other races, as well as those without alcohol use and anti-hypertensive drug use. However, the interaction term only revealed the influence of alcohol consumption on the negative association. CONCLUSION: Our study suggested that urinary chromium concentrations may show a negative association with diastolic blood pressure and this association was significantly dependent on alcohol consumption. Besides, a positive association between urinary chromium and the risk of hypertension was also found among participants older than 60 years of age and those who were Non-Hispanic Black.