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BACKGROUND: The relationship between gut microbiota and vertigo, specifically Benign Paroxysmal Vertigo (BPV) and Vertigo of Central (VC), remains underexplored. AIM AND HYPOTHESES: This study aims to investigate the causal relationships between gut microbiota and two types of vertigo, BPV and VC. Additionally, the study seeks to explore the mediation effects of metabolic, inflammatory, and psychological factors on these relationships. We hypothesize that specific taxa of gut microbiota have a causal effect on the risk of developing BPV and VC. The mediation effects of HbA1c, obesity, major depression, and interleukin-18 levels significantly influence the relationships between gut microbiota and vertigo. METHOD: Utilizing a bidirectional two-sample Mendelian randomization approach, this study investigated causal associations between gut microbiota and the two types of vertigo. A network MR assessed mediation effects of HbA1c, major depression, obesity, and interleukin-18 levels, with data sourced from several consortia, including MiBioGen. RESULTS: Distinct gut microbiota displayed varying influences on BPV and VC risks. A total of ten taxa affect BPV. Among these, two taxa have an odds ratio (OR) greater than 1, including one class, one order. Conversely, eight taxa have an OR less than 1, encompassing four families, three genera, and one order. The OR for these taxa ranges from 0.693 to 0.930, with p-values between 0.006 and 0.048. For VC, eight taxa were found to have an impact. Five of these taxa exhibit an OR greater than 1, including four genera and one phylum. The OR for these taxa ranges from 1.229 to 2.179, with p-values from 0.000 to 0.046. The remaining three taxa have an OR less than 1, comprising one family and two genera, with an OR range of 0.445 to 0.792 and p-values ranging from 0.013 to 0.050. The mediation analysis for BPV shows that major depression, obesity, and HbA1c are key mediators between specific taxa and BPV. Major depression mediates 28.77% of the effect of family Rhodospirillaceae on BPV. Obesity mediates 13.90% of the effect of class Lentisphaeria/order Victivallales. HbA1c mediates 11.79% of the effect of genus Bifidobacterium, 11.36% of family Bifidobacteriaceae/order Bifidobacteriales. For VC, interleukin-18 levels and major depression are significant mediators. Interleukin-18 levels mediate 6.56% of the effect of phylum Actinobacteria. Major depression mediates 6.51% of the effect of genus Alloprevotella. CONCLUSION: The study highlights potential causal links between gut microbiota and vertigo, emphasizing metabolic and psychological mediators. These insights underscore the therapeutic potential of targeting gut health in vertigo management.
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Microbioma Gastrointestinal , Análise da Randomização Mendeliana , Vertigem , Humanos , Microbioma Gastrointestinal/fisiologia , Vertigem/epidemiologia , Vertigem/microbiologia , Vertigem/psicologia , Análise de Mediação , Obesidade/psicologia , Obesidade/microbiologia , Obesidade/epidemiologia , Interleucina-18/sangue , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Transtorno Depressivo Maior/microbiologia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/sangueRESUMO
The function of Family With Sequence Similarity 83, Member A (FAM83A) in lung squamous cell carcinoma (LUSC) is largely unknown. Here, we detected its prognostic and regulation roles in LUSC. Bioinformatics methods were applied initially to predict the expression level and prognostic value of FAM83A mRNA in LUSC. In vitro experiments, such as western blot, colony formation and cell viability assay, lipid Reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG), and 4-hydroxy-2-nonenal (4-HNE) assay, were used to investigate its mechanism. In vivo experiments were further conducted to validate the mechanism. Results from TCGA and Oncomine databases revealed significantly higher FAM83A mRNA expression levels in LUSC than in normal lung tissue. TCGA and GEO databases and our database revealed that FAM83A expression level was an independent prognostic factor for both overall survival and progression-free survival. Besides, FAM83A was significantly associated with a higher ability of growth and clonogenicity. Mechanistically, in vitro and in vivo experiments revealed that FAM83A could promote LUSC cell growth by inhibiting ferroptosis via activating the Wnt/ß-catenin signaling pathway. The rescue experiment demonstrated that inhibition of the Wnt/ß-catenin pathway counteracted the function of FAM83A. FAM83A is overexpressed in LUSC and could serve as a prognosis prediction biomarker for LUSC. FAM83A promotes LUSC cell growth by inhibiting ferroptosis via activating the Wnt/ß-catenin signaling pathway, which provides a new potential therapeutic target for LUSC treatment.
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Enhancing the flame retardancy and durability of cellulose fibers, particularly environmentally friendly regenerated cellulose fibers types like Lyocell fibers, is essential for advancing their broader application. This study introduced a novel approach to address this challenge. Cationic-modified Lyocell fibers (Lyocell@CAT) were prepared by introducing quaternary ammonium structures into the molecular chain of Lyocell fibers. Simultaneously, a flame retardant, APA, containing -COO-NH4+ and -P=O(O-NH4+)2 groups was synthesized. APA was then covalently bonded to Lyocell@CAT to prepare Lyocell@CAT@APA. Even after undergoing 30 laundering cycles (LCs), Lyocell@CAT@APA maintained a LOI value of 37.2 %, exhibiting outstanding flame retardant durability. The quaternary ammonium structure within Lyocell@CAT@APA formed asymmetric ionic bonds with the phosphate and carboxylate groups in APA, effectively shielding the binding of Na+ ions with phosphate groups during laundering, thereby enhancing the durability. Additionally, the consumption of Na+ ions by carboxylate groups further prevented their binding to phosphate groups, which contributed to enhance the durability properties. Flame retardant mechanism analysis revealed that both gas and condensed phase synergistically endowed excellent flame retardancy to Lyocell fibers. Overall, this innovative strategy presented a promising prospect for developing bio-safe, durable, and flame retardant cellulose textiles.
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Celulose , Retardadores de Chama , Celulose/química , Metais/química , Ácidos Carboxílicos/química , Íons/química , Compostos de Amônio Quaternário/químicaRESUMO
Ovarian cancer (OC) is one of the most prevalent and fatal malignant tumors of the female reproductive system. Our research aimed to develop a prognostic model to assist inclinical treatment decision-making.Utilizing data from The Cancer Genome Atlas (TCGA) and copy number variation (CNV) data from the University of California Santa Cruz (UCSC) database, we conducted analyses of differentially expressed genes (DEGs), gene function, and tumor microenvironment (TME) scores in various clusters of OC samples.Next, we classified participants into low-risk and high-risk groups based on the median risk score, thereby dividing both the training group and the entire group accordingly. Overall survival (OS) was significantly reduced in the high-risk group, and two independent prognostic factors were identified: age and risk score. Additionally, three genes-C-X-C Motif Chemokine Ligand 10 (CXCL10), RELB, and Caspase-3 (CASP3)-emerged as potential candidates for an independent prognostic signature with acceptable prognostic value. In Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, pathways related to immune responses and inflammatory cell chemotaxis were identified. Cellular experiments further validated the reliability and precision of our findings. In conclusion, necroptosis-related genes play critical roles in tumor immunity, and our model introduces a novel strategy for predicting the prognosis of OC patients.
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Regulação Neoplásica da Expressão Gênica , Necroptose , Neoplasias Ovarianas , Microambiente Tumoral , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Prognóstico , Necroptose/genética , Microambiente Tumoral/genética , Perfilação da Expressão Gênica , Pessoa de Meia-Idade , Transcriptoma , Biomarcadores Tumorais/genética , Variações do Número de Cópias de DNARESUMO
BACKGROUND: This study aimed to evaluate the efficacy and safety of electroacupuncture (EA) in the treatment of benign prostatic hyperplasia. METHODS: Seven databases were searched from the inception of each database to March 31, 2023, including PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure, Wanfang, and China Biology Medicine. The modified Jadad scale was used to assess literature quality, and literature inclusion and exclusion were conducted in strict accordance with the criteria of a score of ≥4. The risk of bias was evaluated using the Cochrane risk of bias tool. The pooled effect size of the binary data was measured by odds ratio (OR) and 95% confidence interval (CI), and the pooled effect size of the continuous data was presented as weighted mean difference (WMD) and 95% CI. If I² was larger than 50%, a random effects model was adopted, and otherwise, a fixed effects model was used. Additionally, publication bias assessment and sensitivity analysis were conducted. RESULTS: A total of 325 records were retrieved, and finally 9 randomized controlled trial studies were included, involving 1045 patients. Meta-analysis revealed that the EA group had better improvement than the control group in terms of clinical effective rate (odds ratioâ =â 3.92, 95% CIâ =â 2.38 to 6.47, I²â =â 0%, Pâ <â .001), International Prostate Symptom Score (WMDâ =â -4.99, 95% CIâ =â -6.15 to -3.84, I²â =â 76.9%, Pâ <â .001), maximum urinary flow rate (WMDâ =â -4.99, 95% CIâ =â -6.15 to -3.84, I²â =â 87.4%, Pâ <â .001), and post-void residual volume (WMDâ =â -17.12, 95% CIâ =â -29.49 to -4.75, I²â =â 89.1%, Pâ <â .01). There was no statistical significance in prostate volume and adverse events between the EA group and the control group (Pâ >â .05). CONCLUSION: EA is effective in the treatment of benign prostatic hyperplasia with acceptable overall safety.
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Eletroacupuntura , Hiperplasia Prostática , Hiperplasia Prostática/terapia , Humanos , Eletroacupuntura/métodos , Masculino , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Post-stroke spasticity (PSS) is the most common complication of stroke. Acupuncture is widely used in clinical practice for the treatment of PSS, and is therefore considered a common complementary treatment. Several systematic reviews (SRs) and meta-analyses (MAs) have demonstrated the efficacy and safety of acupuncture in the treatment of PSS; however, the quality of evidence of these studies has not been adequately assessed. OBJECTIVE: To evaluate and summarize the SRs/MAs and inform future research and clinical practice on the efficacy and safety of acupuncture for PSS. DATA SOURCES AND EXTRACION: The following databases were searched from their dates of inception to March 26, 2023: PubMed, Embase, The Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, SinoMed, and Chinese Science and Technology Periodical Database (VIP), and grey literature were manually searched. Two reviewers independently completed literature retrieval, screening, and data extraction. REVIEW APPRAISAL: Systematic evaluation tools to Assess Systematic Reviews (AMSTAR) 2, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020 Checklist), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system were used to systematically evaluate the methodological, reporting, and evidence quality of the SRs/MAs. RESULTS: Overall, 226 papers were examined, and after careful consideration, 10 SRs/MAs were deemed eligible for inclusion. The AMSTAR 2 assessment revealed that one SR/MA had medium, one study had low, and the remaining eight studies had critically low methodological qualities. Additionally, four SRs/MAs completed more than 60 % of the PRISMA 2020 checklist. The GRADE system indicated that six outcomes were medium, 26 outcomes were low, and 24 outcomes were critically low. CONCLUSION: Based on the evidence, acupuncture may be a promising complementary treatment to improve post-stroke spasticity and quality of life. Further high-quality RCTs are needed in future studies to support the broader application of acupuncture for the treatment of PSS.
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Terapia por Acupuntura , Acidente Vascular Cerebral , Humanos , Bases de Dados Factuais , Espasticidade Muscular/etiologia , Espasticidade Muscular/terapia , Qualidade de Vida , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Revisões Sistemáticas como AssuntoRESUMO
Stroke is the third leading cause of death and disability worldwide. Post-stroke spasticity (PSS) is the most common complication of stroke but represents only one of the many manifestations of upper motor neuron syndrome. As an upper motor neuron, the corticospinal tract (CST) is the only direct descending motor pathway that innervates the spinal motor neurons and is closely related to the recovery of limb function in patients with PSS. Therefore, promoting axonal remodeling in the CST may help identify new therapeutic strategies for PSS. In this review, we outline the pathological mechanisms of PSS, specifically their relationship with CST, and therapeutic strategies for axonal regeneration of the CST after stroke. We found it to be closely associated with astroglial scarring produced by astrocyte activation and its secretion of neurotrophic factors, mainly after the onset of cerebral ischemia. We hope that this review offers insight into the relationship between CST and PSS and provides a basis for further studies.
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Tratos Piramidais , Acidente Vascular Cerebral , Humanos , Tratos Piramidais/patologia , Axônios/patologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Neurônios Motores/patologia , Recuperação de Função Fisiológica/fisiologiaRESUMO
Hypoxanthine phosphoribosyl transferase 1 (HPRT1), once considered a housekeeping gene, has been identified as playing an important role in several tumors. Its role in pan-cancer, however, has not been systematically studied. This study evaluates the relationship between HPRT1 and clinical parameters, survival prognosis, and tumor immunity based on multi omics data from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Drug sensitivity analysis screened 16 effective drugs against HPRT1, exploring the interactions with chemicals and genes. The significance of HPRT1 in tumor immunotherapy has also been investigated. Immunohistochemistry confirmed significant differences in the expression of HPRT1 between five tumor types (colon adenocarcinoma [COAD], head-neck squamous cell carcinoma [HNSC], lung adenocarcinoma [LUAD], thyroid carcinoma [THCA], and uterine corpus endometrial carcinoma [UCEC]) and adjacent normal tissues (P < 0.05). HPRT1 competitive endogenous RNA network was constructed in HNSC. Through cytological experiments, it was verified that HPRT1 plays a carcinogenic role in HNSC and is associated with tumor cell proliferation, migration, invasion, and apoptosis. In addition, there was a significant positive correlation between HPRT1 and programmed cell death-1 (PD-1) expression in HNSC (P < 0.05). These findings suggest that HPRT1 may be a potential biomarker for predicting and treating cancer.
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Adenocarcinoma , Neoplasias do Colo , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Humanos , Prognóstico , Hipoxantina FosforribosiltransferaseRESUMO
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is identified as the cause of coronavirus disease 2019 (COVID-19) pandemic. Acute kidney injury (AKI), one of serious complications of COVID-19 infection, is the leading contributor to renal failure, associating with high mortality of the patients. This study aimed to identify the shared gene signatures and construct the gene regulatory network between COVID-19 and AKI, contributing to exploring the potential pathogenesis. METHODS: Utilizing the machine learning approach, the candidate gene signatures were derived from the common differentially expressed genes (DEGs) obtained from COVID-19 and AKI. Subsequently, receiver operating characteristic (ROC), consensus clustering and functional enrichment analyses were performed. Finally, protein-protein interaction (PPI) network, transcription factor (TF)-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory network were systematically undertaken. RESULTS: We successfully identified the shared 6 candidate gene signatures (RRM2, EGF, TMEM252, RARRES1, COL6A3, CUBN) between COVID-19 and AKI. ROC analysis showed that the model constructed by 6 gene signatures had a high predictive efficacy in COVID-19 (AUC = 0.965) and AKI (AUC = 0.962) cohorts, which had the potential to be the shared diagnostic biomarkers for COVID-19 and AKI. Additionally, the comprehensive gene regulatory networks, including PPI, TF-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory networks were displayed utilizing NetworkAnalyst platform. CONCLUSIONS: This study successfully identified the shared gene signatures and constructed the comprehensive gene regulatory network between COVID-19 and AKI, which contributed to predicting patients' prognosis and providing new ideas for developing therapeutic targets for COVID-19 and AKI.
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Injúria Renal Aguda , COVID-19 , MicroRNAs , Humanos , COVID-19/genética , SARS-CoV-2/genética , Injúria Renal Aguda/genética , Análise por Conglomerados , Proteínas de MembranaRESUMO
BACKGROUND: The dose-effect relationship of Long-snake-like moxibustion for chronic fatigue syndrome (CFS) remains poorly understood. In order to address this gap, we designed this trial to assess the association between different treatment duration of Long-snake-like moxibustion and its effects on CFS based on the combination measurements of the subjective patient-reported scales with objective medical infrared imaging technologyâThermal Texture Maps (TTM). METHODS: From December 2020 to January 2022, 60 female CFS patients were recruited and equally allocated to two groups: Group A, receiving 60-min Long-snake-like moxibustion per treatment, and Group B, receiving 30-min Long-snake-like moxibustion per treatment. The treatment was administered 3 times per week for a total of 4 weeks. The primary outcome was defined as the improvement of symptoms measured by the Fatigue scale-14 (FS-14), and secondary outcomes were designated as the improvement in Symptoms Scale of Spleen-Kidney Yang Deficiency, Self-rating depression scale, and Self-rating anxiety scale. TTM scanning was employed twice for CFS patients (before and after 4-week treatment) and once for Healthy control subjects (HCs). RESULTS: At week 4, the scores of FS-14 and Symptoms Scale of Spleen-Kidney Yang Deficiency in Group A were significantly lower than those in Group B (physical fatigue: 5.00 vs. 6.00, with 95%CI - 2.00 to 0.00, p = 0.003; FS-14 total score: 8.00 vs. 9.00, with 95%CI - 3.00 to 0.00, p = 0.012; total score of Symptoms Scale of Spleen-Kidney Yang Deficiency: 9.80 vs. 13.07, with 95%CI - 5.78 to - 0.76, P = 0.012). All thermal radiation values of the two groups increased, and statistical differences in ΔTs between Group A and HCs were not obtained. More significant correlations between symptoms improvements and ΔT changes were observed in Group A, and its ΔT changes in Upper Jiao, Shenque (CV8), Zhongwan (CV12), Danzhong (CV17), Zhiyang (GV9), Dazhui (GV14), upper arm, thoracic segments, lumbar segments, renal region, popliteal fossa strongly correlated with the improvement of Spleen-Kidney Yang Deficiency symptoms. CONCLUSIONS: In the same course of treatment, the positive dose-effect relationship was found between the treatment duration of Long-snake-like moxibustion and CFS effect assessment. 60-min Long-snake-like moxibustion per treatment were associated with optimal clinical response and TTM improvement. TRIAL REGISTRATION: Chinese Clinical Trail Registry (No. ChiCTR2000041000, date of registration: 16 December 2020), http://www.chictr.org.cn/showproj.aspx?proj=62488.
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Síndrome de Fadiga Crônica , Moxibustão , Humanos , Feminino , Moxibustão/métodos , Síndrome de Fadiga Crônica/terapia , Deficiência da Energia Yang/terapia , Pontos de Acupuntura , BaçoRESUMO
Oral squamous cell carcinoma (OSCC) still threatens people's daily life. METTL14 is a newly discovered methyltransferase that catalyzes m6A methylation. Hence, this research was carried out to investigate the action mechanism of METTL14 in OSCC. The SCC-4 and UM2 cells, and tumorigenicity assay were utilized to investigate METTL14 roles in vitro and in vivo. Bioinformatic analysis was carried out with the UCSC, TCGA database and The Human Protein Atlas. The gene expression at mRNA and protein levels were measured by qRT-PCR and Western blot. In addition, cell growth and metastasis was analyzed by colony formation and transwell assays. MeRIP assay was performed to test the m6A levels of CALD1. The METTL14 and CALD1 levels were prominently expressed in OSCC cells. METTL14 silencing depleted the cell growth and metastasis. Furthermore, METTL14 silencing depleted the tumor growth in vivo. Additionally, the mRNA and m6A levels of CALD1 were depleted after METTL14 silencing. Overexpressed CALD1 neutralized the si-METTL14 effects in OSCC cells. In conclusion, METTL14 participated in the OSCC progression through modulating the mRNA and m6A levels of CALD1.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Metiltransferases , RNA Mensageiro , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
CONTEXT: Gestational diabetes mellitus (GDM) is a common obstetric complication. Although early intervention could prevent the development of GDM, there was no consensus on early identification for women at high risk of GDM. OBJECTIVE: To develop a reliable prediction model of GDM in early pregnancy. METHODS: In this prospective cohort study, between May 30, 2021, and August 13, 2022, a total of 721 women were included from Women's Hospital, Zhejiang University School of Medicine. Participants were asked to complete an oral glucose tolerance test (OGTT) during gestational weeks 7 through 14 for early prediction of GDM, and at weeks 24 through 28 for GDM diagnosis. Using OGTT results and baseline characteristics, logistic regression analysis was used to construct the prediction model. Receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test, decision clinical analysis, and a nomogram were used for model performances assessment and visualization. Internal and external validation was performed to testify the stability of this model. RESULTS: According to the International Association of Diabetes and Pregnancy Study Groups criteria in early OGTT, the mean (SD) age was 30.5 ± 3.7 years in low-risk participants and 31.0 ± 3.9 years in high-risk participants. The area under ROC curve (AUC) of the existing criteria at weeks 7 through 14 varied from 0.705 to 0.724. Based on maternal age, prepregnancy body mass index, and results of early OGTT, the AUC of our prediction model was 0.8720, which was validated by both internal (AUC 0.8541) and external (AUC 0.8241) confirmation. CONCLUSIONS: The existing diagnostic criteria were unsatisfactory for early prediction of GDM. By combining early OGTT, we provided an effective prediction model of GDM in the first trimester.
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Diabetes Gestacional , Gravidez , Feminino , Humanos , Adulto , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Teste de Tolerância a Glucose , Estudos Prospectivos , Idade Materna , Medição de RiscoRESUMO
Background: The most common type of glomerulonephritis in China is mesangial proliferative glomerulonephritis (MPGN) featured with mesangial cell overproliferation and inflammation, as well as fibrosis. Albiflorin (AF) is an effective composition extracted from Paeonia Alba Radix and has been administrated for various diseases. Nevertheless, there is no research reporting the effect of AF on MPGN.Purpose: Our work aims to probe into the role and possible mechanism of AF on MPGN.Research Design: We investigated the effects of AF on mesangial cell overproliferation, inflammation, and fibrosis in vitro and in vivo and identified the related signaling pathways.Study Sample: human mesangial cells (HMCs) and male Sprague Dawley (SD) rats.Data Analysis: SPSS 18.0 was used to analyze the data.Results: AF attenuated the proliferation and inflammation both in vitro and in vivo. In detail, AF decreased the ki67 expression in lipopolysaccharides (LPS)-treated HMCs and MPGN rats, and the mRNA expression or contents of inflammatory cytokines were reduced after AF treatment. The fibrosis of LPS-treated HMCs and MPGN rats was also reduced by AF. Moreover, AF effectively restrained 24 h urinary protein, improved kidney function, and mitigated dyslipidemia and pathological injury of MPGN rats. Additionally, we found that the protective effects of AF were accompanied by the blocking of PI3K/AKT/NF-κB pathway, and the inhibitory effects of AF on MPGN were reversed by insulin-like growth factor (IGF-1), the PI3K agonist.Conclusions: AF alleviates MPGN via restraining mesangial cell overproliferation, inflammation, and fibrosis via PI3K/AKT/NF-κB signaling.
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Glomerulonefrite , NF-kappa B , Ratos , Masculino , Humanos , Animais , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases , Ratos Sprague-Dawley , Lipopolissacarídeos , Glomerulonefrite/tratamento farmacológico , Inflamação , FibroseRESUMO
RATIONALE AND OBJECTIVES: Nottingham histological grade (NHG) 2 breast cancer has an intermediate risk of recurrence, which is not informative for therapeutic decision-making. We sought to develop and independently validate an MRI-based radiomics signature (Rad-Grade) to improve prognostic re-stratification of NHG 2 tumors. MATERIALS AND METHODS: Nine hundred-eight subjects with invasive breast cancer and preoperative MRI scans were retrospectively obtained. The NHG 1 and 3 tumors were randomly split into training and independent test cohort, with the NHG 2 as the prognostic validation set. From MRI image features, a radiomics-based signature predictive of the histological grade was built by use of the LASSO logistic regression algorithm. The model was developed for identifying NHG 1 and 3 radiological patterns, followed with re-stratification of NHG 2 tumors into Rad-Grade (RG)2-low (NHG 1-like) and RG2-high (NHG 3-like) subtypes using the learned patterns, and the prognostic value was assessed in terms of recurrence-free survival (RFS). RESULTS: The Rad-Grade showed independent prognostic value for re-stratification of NHG 2 tumors, where RG2-high had an increased risk for recurrence (HR 2.20, 1.10-4.40, p = 0.026) compared with RG2-low after adjusting for established risk factors. RG2-low shared similar phenotypic characteristics and RFS outcomes with NHG 1, and RG2-high with NHG 3, revealing that the model captures radiomic features in NHG 2 that are associated with different aggressiveness. The prognostic value of Rad-Grade was further validated in the NHG2 ER+ (HR 2.53, 1.13-5.56, p = 0.023) and NHG 2 ER+LN- (HR 5.72, 1.24-26.44, p = 0.025) subgroups, and in specific treatment contexts. CONCLUSION: The radiomics-based re-stratification of NHG 2 tumors offers a cost-effective promising alternative to gene expression profiling for tumor grading and thus may improve clinical decisions.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Prognóstico , Gradação de TumoresRESUMO
The use of assisted reproductive technology (ART) has risen steadily worldwide over the past 3 decades and helps many infertile families. However, ART treatments lead to an abnormal internal environment in the uterus, which may increase the risks of health problems for the offspring. Higher maternal estradiol (E2) is a notable feature in women who use ART treatments, and this has been suggested as a key factor for the risk of diseases in the offspring. In the current study, we have established a marmoset model with a high E2 level in early pregnancy to examine its potential risk to the development and behavior of the offspring. In comparison with the normal group, babies of the high E2 group exhibited lower average survival rates and birth weights. However, those who survived in the high E2 group demonstrated normal vocal production with rich call repertoires, normal speed during locomotion, and normal behaviors in the home cage. In contrast to the normal group, surviving babies of the high E2 group spent more time sleeping during development without signs of sleep disorders. In summary, our study revealed that high estrogen in early pregnancy may cause low survival rates and birth weights of the offspring, though the surviving infants did not show obvious behavioral deficiencies during development. The current study is a valuable and highly important non-human primate study for evaluating the safety of ART treatments. However, it is worth noting that some results did not reach the significant level, which may be due to the small sample size caused by animal shortage stemming from the COVID-19 epidemic.
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Primary ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by premature exhaustion of primordial follicles. POI causes infertility, severe daily life disturbances and long-term health risks. However, the underlying mechanism remains largely unknown. We previously identified a Basonuclin 1 (BNC1) mutation from a large Chinese POI pedigree and found that mice with targeted Bnc1 mutation exhibit symptoms of POI. In this study, we found that BNC1 plays key roles in ovarian reserve and maintaining lipid metabolism and redox homeostasis in oocytes during follicle development. Deficiency of BNC1 results in premature follicular activation and excessive follicular atresia. Mechanistically, BNC1 deficiency triggers oocyte ferroptosis via the NF2-YAP pathway. We demonstrated that pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced POI. These findings uncover a pathologic mechanism of POI based on BNC1 deficiency and suggest YAP and ferroptosis inhibitors as potential therapeutic targets for POI.
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Ferroptose , Insuficiência Ovariana Primária , Animais , Proteínas de Ligação a DNA/metabolismo , Feminino , Atresia Folicular , Humanos , Camundongos , Oócitos/metabolismo , Folículo Ovariano/metabolismo , Insuficiência Ovariana Primária/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Infertility affects about 10-15% couples over the world, among which a large number of cases the underlying causes are still unclear. Recent studies suggest that environmental factors may play an important role in these idiopathic infertilities. Arsenic is a heavy metal found in drinking water over the world. Its effect on the development of female reproductive system at the environmental-relevant levels is still largely unknown. To test the hypothesis that arsenic exposure during juvenile and puberty may affect sex maturation and female reproductive system development, SD rats of 3 weeks of age were exposed to arsenic with environmental-relevant levels (0, 0.02, 0.2, or 2 mg/L, n = 16/group) through drinking water for about 44 days until the rats reached adulthood (65 days of age). Arsenic exposure significantly reduced the weights of both ovary and uterus without affecting the body weight. Also, arsenic exposure disturbed estrus cycles and reduced the numbers of primordial follicles and corpora lutea while increased atretic follicles. In addition, arsenic reduced serum levels of estradiol, progesterone and testosterone but increased LH and FSH levels in dose-dependent manners. QPCR and Western blot experiments indicated arsenic selectively down-regulated ovarian steroidogenic-related proteins FSHR, STAR, CYP17A1, HSD3B1 and CYP19A1 and signaling molecules PKA-ERK-JNK-cJUN, without affecting AKT and CREB. As about reproductive capacity, arsenic-exposed dams had smaller pups, reduced litter size and lower number of male pups without a change in female pups. In conclusion, juvenile and pubertal arsenic exposures at environmental-relevant levels significantly reduced reproductive functions and capacity by adult. Since the lowest effective dose is very close to the government safety standards, the relevancy of arsenic over exposure to reproductive defects in human deserves further study.
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Arsênio , Água Potável , Adulto , Animais , Arsênio/metabolismo , Feminino , Humanos , Masculino , Ovário , Ratos , Ratos Sprague-Dawley , Maturidade SexualRESUMO
BACKGROUND: Nondiabetic kidney disease (NDKD), which is prevalent among patients with diabetes mellitus (DM), is considerably different from diabetic kidney disease (DKD) in terms of the pathological features, treatment strategy and prognosis. Although renal biopsy is the current gold-standard diagnostic method, it cannot be routinely performed due to a range of risks. The aim of this study was to explore the predictors for differentiating NDKD from DKD to meet the urgent medical needs of patients who cannot afford kidney biopsy. METHODS: This is a retrospective study conducted by reviewing the medical records of patients with type 2 DM who underwent percutaneous renal biopsy at the Affiliated Hospital of Guizhou Medical University between January 2017 and May 2021. The demographic data, clinical data, blood test results, and pathological examination results of the patients were obtained from their medical records. Multivariate regression analysis was performed to evaluate the predictive factors for NDKD. RESULTS: A total of 244 patients were analyzed. The median age at biopsy was 55 (46, 62) years. Patients diagnosed with true DKD, those diagnosed with NDKD and those diagnosed with NDKD superimposed DKD represented 48.36% (118/244), 45.9% (112/244) and 5.74% (14/244), respectively, of the patient population. Immunoglobulin A nephropathy was the most common type of lesion in those with NDKD (59, 52.68%) and NDKD superimposed DKD (10, 71.43%). Independent predictive indicators for diagnosing NDKD included a DM duration of less than 5 years (odds ratio [OR] = 4.476; 95% confidence interval [CI]: 2.257-8.877; P < 0.001), an absence of diabetic retinopathy (OR = 4.174; 95% CI: 2.049-8.502; P < 0.001), a high RBC count (OR = 1.901; 95% CI: 1.251-2.889; P = 0.003), and a negative of urinary glucose excretion test result (OR = 2.985; 95% CI: 1.474-6.044; P = 0.002).. CONCLUSIONS: A DM duration less than 5 years, an absence of retinopathy, a high RBC count and an absence of urinary glucose excretion were independent indicators for the diagnosis of NDKD, suggesting that patients with NDKD may require a different treatment regimen than those with DKD.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Retinopatia Diabética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Retinopatia Diabética/patologia , Glucose , Humanos , Rim , Estudos RetrospectivosRESUMO
BACKGROUND: Two or more embryo transfers have been used to increase the success rate of live birth in traditional in vitro fertilization (IVF) strategy at the expense of increased risks of multiple pregnancy and adverse perinatal outcomes. The decision regarding the elective single embryo transfer or double embryo transfer remains inconclusive. The aim of this study was to investigate the risk factors for twin pregnancy in IVF. METHODS: Participants who underwent their first fresh IVF cycle where two cleavage stage embryos were transferred in Women's Hospital of Zhejiang University between January 2010 and December 2018 were included in this retrospective cohort study. The primary outcome was twin delivery. Secondary outcomes included preterm birth and low birth weight RESULTS: Fifteen thousand four hundred fifty-nine women were available for final analysis, in which 1511 women resulted in twin delivery and 4788 women had singleton delivery. Female age over 35 was associated with reduced rates of twin pregnancy compared with female age at or less than 35 (9.5% vs 25.1%, aRR = 0.38 (0.27. 0.55)). Poor-type endometrium was associated with reduced rates of twin pregnancy (19.2% vs 27.5%, aRR = 0.75 (0.58. 0.96)). Two good-quality embryos for transfer was associated with significantly higher rates of twin pregnancy compared with one good-quality or none good-quality embryo (26% vs 12.8% vs 9.3%, aRR = 0.56 (0.45. 0.70), aRR = 0.44(0.26. 0.74)). Female age over 35 and none or one good-quality embryo for transfer were associated with reduced rate of low birth weight and preterm birth. CONCLUSION: Women with age over 35, poor-type endometrium, one good-quality embryo or none good-quality embryo were associated with reduced rate for twin pregnancy.