RESUMO
The nuclear factor κappa B (NF-κB) signaling plays a well-known function in inflammation and regulates a wide variety of biological processes. Low-grade chronic inflammation is gradually considered to be closely related to the pathogenesis of Polycystic ovary syndrome (PCOS). In this review, we provide an overview on the involvement of NF-κB in the progression of PCOS particularly, such as hyperandrogenemia, insulin resistance, cardiovascular diseases, and endometrial dysfunction. From a clinical perspective, progressive recognition of NF-κB pathway provides opportunities for therapeutic interventions aimed at inhibiting pathway-specific mechanisms. With the accumulation of basic experimental and clinical data, NF-κB signaling pathway was recognized as a therapeutic target. Although there have been no specific small molecule NF-κB inhibitors in PCOS, a plethora of natural and synthetic compound have emerged for the pharmacologic intervention of the pathway. The traditional herbs developed for NF-κB pathway have become increasingly popular in recent years. Abundant evidence elucidated that NF-κB inhibitors can significantly improve the symptoms of PCOS. Herein, we summarized evidence relating to how NF-κB pathway is involved in the development and progression of PCOS. Furthermore, we present an in-depth overview of NF-κB inhibitors for therapy interventions of PCOS. Taken together, the NF-κB signaling may be a futuristic treatment strategy for PCOS.
Assuntos
NF-kappa B , Síndrome do Ovário Policístico , Feminino , Humanos , Inflamação/tratamento farmacológico , Resistência à Insulina , NF-kappa B/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Transdução de Sinais , Doenças CardiovascularesRESUMO
The female reproductive system comprises the internal and external genitalia, which communicate through intricate endocrine pathways. Besides secreting hormones that maintain the female secondary sexual characteristics, it also produces follicles and offspring. However, the in vitro systems have been very limited in recapitulating the specific anatomy and pathophysiology of women. Organ-on-a-chip technology, based on microfluidics, can better simulate the cellular microenvironment in vivo, opening a new field for the basic and clinical research of female reproductive system diseases. This technology can not only reconstruct the organ structure but also emulate the organ function as much as possible. The precisely controlled fluidic microenvironment provided by microfluidics vividly mimics the complex endocrine hormone crosstalk among various organs of the female reproductive system, making it a powerful preclinical tool and the future of pathophysiological models of the female reproductive system. Here, we review the research on the application of organ-on-a-chip platforms in the female reproductive systems, focusing on the latest progress in developing models that reproduce the physiological functions or disease features of female reproductive organs and tissues, and highlighting the challenges and future directions in this field.
Assuntos
Genitália Feminina , Dispositivos Lab-On-A-Chip , Feminino , Humanos , Animais , Microfluídica/métodos , Reprodução , Modelos Biológicos , Sistemas MicrofisiológicosRESUMO
PURPOSE: The purpose of our study is to investigate the function of YAP1 in the trophoblast ferroptosis and maternal-fetal interface communication of RPL. METHODS: We collected 25 villous tissues and detected the expression of YAP1. Cell counting kit-8 assay, scratch wound-healing assay, and Matrigel invasion assay were performed to observe the proliferation, migration, and invasion of HTR-8/SVneo and JAR cells. Subsequently, measured the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH), SLC7A11, SOD2, and GPX4. Ultimately, the use of ferroptosis activator (erastin) and inhibitor (Ferrostatin-1, fer-1) further confirmed the regulation by YAP1. In addition, established an in vitro-induced cell model to study the effect of YAP1 on the decidualization process. Finally, animal models were implemented for further confirmation. RESULTS: We found that YAP1 was downregulated in RPL patients. Overexpression of YAP1 could significantly enhance the proliferation, migration, and invasion of trophoblasts, and inhibit ferroptosis. Knocking down YAP1 exhibited the opposite effect. Rescue experiments have shown that YAP1 could upregulate the expression of SLC7A11 and GPX4, which are key molecules in the classic pathway of ferroptosis. In addition, the decidualization was impaired when hESCs were treated with conditioned medium of YAP1 knockdown trophoblasts. Moreover, we found that Yap1, Slc7a11, and Gpx4 were downregulated in the RPL mice, along with increased MDA and decreased GSH. CONCLUSION: Downregulation of YAP1 induces ferroptosis, thereby damaging the trophoblast invasion processes, which also disturbs the communication at the maternal-fetal interface. Our study identified YAP1 as a potential key molecule in the pathogenesis of RPL.
Assuntos
Aborto Habitual , Proliferação de Células , Ferroptose , Trofoblastos , Proteínas de Sinalização YAP , Adulto , Animais , Feminino , Humanos , Camundongos , Gravidez , Aborto Habitual/patologia , Aborto Habitual/genética , Aborto Habitual/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Ferroptose/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patologia , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genéticaRESUMO
OBJECTIVE: To explore the expressions of zinc homeostasis-related proteins, G protein-coupled receptor 39 (GPR39) and ANO1 mRNA in the sperm of patients with asthenozoospermia (AS), and analyze their correlation with sperm motility. METHODS: We collected semen samples from 82 male subjects with PR+NP < 40%, PR < 32% and sperm concentration > 15×106/ml (the AS group, n = 40) or PR+NP ≥ 40%, PR ≥ 32% and sperm concentration > 15×106/ml (the normal control group, n = 42). We analyzed the routine semen parameters and measured the zinc content in the seminal plasma using the computer-assisted sperm analysis system, detected the expressions of zinc transporters (ZIP13, ZIP8 and ZNT10), metallothioneins (MT1G, MT1 and MTF), GPR39, and calcium-dependent chloride channel protein (ANO1) in the sperm by real-time quantitative PCR (RT qPCR), examined free zinc distribution in the sperm by laser confocal microscopy, and determined the expressions of GPR39 and MT1 proteins in the sperm by immunofluorescence staining, followed by Spearman rank correlation analysis of their correlation with semen parameters. RESULTS: There was no statistically significant difference in the zinc concentration in the seminal plasma between the AS and normal control groups (P>0.05). Compared with the controls, the AS patients showed a significantly reduced free zinc level (P<0.05), relative expressions of MT1G, MTF, ZIP13, GPR39 and ANO1 mRNA (P<0.05), and that of the GPR39 protein in the AS group (P<0.05). No statistically significant differences were observed in the relative expression levels of ZIP8, ZNT10 and MT1 mRNA between the two groups (P>0.05). The relative expression levels of GPR39, ANO1, MT1G and MTF mRNA were positively correlated with sperm motility and the percentage of progressively motile sperm (P<0.05). CONCLUSION: The expressions of zinc homeostasis proteins (MT1G, MTF and ZIP13), GPR39 and ANO1 mRNA are downregulated in the sperm of asthenozoospermia patients, and positively correlated with sperm motility.
Assuntos
Anoctamina-1 , Astenozoospermia , Proteínas de Transporte de Cátions , RNA Mensageiro , Receptores Acoplados a Proteínas G , Motilidade dos Espermatozoides , Espermatozoides , Zinco , Humanos , Masculino , Astenozoospermia/metabolismo , Astenozoospermia/genética , Anoctamina-1/metabolismo , Anoctamina-1/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Zinco/metabolismo , Espermatozoides/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Metalotioneína/metabolismo , Metalotioneína/genética , Homeostase , Adulto , Análise do Sêmen , Relevância Clínica , Proteínas de NeoplasiasRESUMO
Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting women. Chinese herbs have been considered as an alternative treatment for PCOS, and Yi-mu-cao (Leonuri Herba) is one of the most commonly used herbs to treat PCOS, which can relieve symptoms of PCOS patients. But the mechanism of its treatment remains unclear. Method: The main active ingredients and potential targets of Leonuri Herba were obtained by TCMSP and Swiss Target Forecast, and the related targets of PCOS were obtained by searching DrugBank, GeneCard and DisGeNet databases. The Protein-Protein Interaction (PPI) network was constructed using STRING database. GO and KEGG were used to detect the enrichment pathways of key targets. Cytoscape software was used to construct the component-target-pathway network, analyze the PPI network core, and verify the reliability of target binding by molecular docking technology. Result: 8 components and 116 targets of Leonuri Herba on PCOS were screened. Common targets mainly involve the Lipid and atherosclerosis, Endocrine resistance, AGE-RAGE signaling in diabetic complications and other signaling pathways. It is suggested that it can form multi-target and multi-pathway regulatory network through quercetin, kaempferol and other active substances to regulate endocrine disorders and reduce inflammatory response, so as to systematically improve PCOS. Molecular docking experiments showed that the active constituents of Leonurus had good binding activity with potential targets of PCOS. Conclusion: In summary, this study elucidates the potential effect of Leonuri Herba on PCOS, which is helpful to provide reference for clinical practice. This is also conducive to the secondary development of motherwort and its monomer components, and precision medicine for PCOS.
Assuntos
Aterosclerose , Medicamentos de Ervas Chinesas , Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Reprodutibilidade dos Testes , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional ChinesaRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) has unusual levels of hormones. The hormone receptors in the endometrium have a hostile effect and make the microenvironment unfavorable for embryo implantation. The use of gonadotropin stimulation during in vitro fertilization (IVF) may have an impact on embryo implantation and live birth rate. According to recent data, the clinical results of day 4 embryo transfer (D4 transfer) were on par with those of day 5 embryo transfer (D5 transfer) in IVF-ET. There are few studies comparing the outcomes of transplants with various etiologies and days. The purpose of this study was to determine which transfer day had the best result for PCOS patients undergoing IVF. METHODS: This retrospective cohort study was conducted in the Xingtai Infertility Specialist Hospital between January 2017 and November 2021. A total of 1,664 fresh ART cycles met inclusion criteria, including 242 PCOS transfers and 1422 tubal factor infertility transfers. CONCLUSIONS: PCOS individuals had the highest live birth rate on D4 transferred. It was not need to culture embryos to blastocysts to optimize embryo transfer for PCOS women. This could be a novel approach to transplantation for PCOS.
Assuntos
Infertilidade , Síndrome do Ovário Policístico , Humanos , Feminino , Gravidez , Coeficiente de Natalidade , Síndrome do Ovário Policístico/complicações , Estudos Retrospectivos , Fertilização in vitro/métodos , Nascido Vivo/epidemiologia , Taxa de Gravidez , Microambiente TumoralRESUMO
Heavy metal ions seriously threaten human health; even a trace of them can damage the renal, nervous, and immune systems irreversibly. Although established nanozyme-based colorimetric assays have been designed for the rapid detection of heavy metal ions, the general contained surface organic ligands of nanocatalysts and low absorptivity of metal ions on solid substrates might result in a weak effect on active sites and prevent the realization of their full detection potential. Here, we developed a nanozyme-based colorimetric sensor (CPM-Pt) made by pyrolysis of peat moss with preabsorbed traces of Pt ions to ultrasensitively detect Ag+. The calcination removes organic components and produces bare nanozymes that expose rich active sites. The strong protective effect from the porous carbon support enables the embedded Pt nanoparticles (Pt NPs) with a partially stable positive charge after pyrolysis (â¼28% Pt2+ species). By the d8-d10 metal-metal interactions between Pt2+ (4f145d8) and Ag+ (4d10), the high proportion of Pt2+ species on the surface of Pt NPs can readily capture/absorb Ag+. Subsequently, Ag+ accepts electrons from the support to form Ag atoms, which rapidly cover the peroxidase-like active sites of bare Pt NPs, weakening the activation of H2O2 to realize the response of Ag+. The colorimetric detection limit of Ag+ reached an unprecedented 1.1 pM, and the corresponding naked-eye color recognition is ultrasensitive to extremely low levels (100 pM).
Assuntos
Nanopartículas Metálicas , Metais Pesados , Domínio Catalítico , Colorimetria , Humanos , Peróxido de Hidrogênio/química , Íons , Nanopartículas Metálicas/química , Prata/químicaRESUMO
Pregnancy is a complex biological process. The establishment and maintenance of foetal-maternal interface are pivotal events. Decidual immune cells and inflammatory cytokines play indispensable roles in the foetal-maternal interface. The disfunction of decidual immune cells leads to adverse pregnancy outcome. Tumour necrosis factor (TNF)-α, a common inflammatory cytokine, has critical roles in different stages of normal pregnancy process. However, the relationship between the disorder of TNF-α and adverse pregnancy outcomes, including preeclampsia (PE), intrauterine growth restriction (IUGR), spontaneous abortion (SA), preterm birth and so on, is still indefinite. In this review, we thoroughly reviewed the effect of TNF-α disorder on pathological conditions. Moreover, we summarized the reports about the adverse pregnancy outcomes (PE, IUGR, SA and preterm birth) of using anti-TNF-α drugs (infliximab, etanercept and adalimumab, certolizumab and golimumab) currently in the clinical studies. Overall, IUGR, SA and preterm birth are the most common adverse pregnancy outcomes of anti-TNF-α drugs. Our review may provide insight for the immunological treatment of pregnancy-related complication, and help practitioners make informed decisions based on the current evidences.
Assuntos
Aborto Espontâneo , Pré-Eclâmpsia , Complicações na Gravidez , Nascimento Prematuro , Aborto Espontâneo/induzido quimicamente , Adalimumab/efeitos adversos , Citocinas , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/etiologia , Humanos , Recém-Nascido , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/etiologia , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Nascimento Prematuro/induzido quimicamente , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfaRESUMO
Persistent organic pollutants (POPs) have a huge impact on human health due to their high toxicity and non-degradability. It is still of great difficulty to develop highly efficient catalysts toward the degradation of POPs. Herein, it is reported that regulating electronic structure of quasi-single atomic ferric iron (Fe(III)) in the VO2 support through the electronic metal-support interaction (EMSI) is a versatile strategy to enhance the catalytic activity. Activated Fe(III) can react with peroxydisulfate (PDS) to produce both radicals and high-valent iron (HVFe) simultaneously for the efficient and fast degradation of POPs. Density functional theory (DFT) calculations prove that the influence of EMSI promotes the electrons on Fe(III) 3d-bond center moving close to the Fermi level, facilitating the charge transfer from Fe(III) to the adsorbate. Through the control experiments, both the radical path by PDS and the HVFe path aroused by the EMSI are confirmed in the POP degradation process. Consequently, the Fe/VO2 catalyst exhibits record-breaking catalytic activity with the k-value as high as 56.7, 43.3 µmol s-1 g-1 for p-chlorophenol and 2,4-dichlorophenol degradation, respectively.
Assuntos
Compostos Férricos , Ferro , Catálise , Eletrônica , Humanos , Ferro/química , OxirreduçãoRESUMO
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women, with clinical manifestations of anovulation and hyperandrogenaemia. The treatment of PCOS mainly focuses on improving clinical symptoms, such as insulin sensitivity or menstrual disorder, through drug treatment. However, due to the pathogenesis diversity of PCOS, there is still a lack of effective treatment in clinics. Metabolic disorder is the key factor in the occurrence of PCOS. Brown adipose tissue (BAT) is a special adipose tissue in the human body that can participate in metabolic balance by improving heat production. BAT has been demonstrated to be an important substance involved in the metabolic disorder of PCOS. Although increasing evidence indicates that BAT transplantation can improve the symptoms of PCOS, it is difficult to achieve BAT transplantation at present due to technical limitations. Stimulation of BAT activation by exogenous substances may be an effective alternative therapy for PCOS. In this study, we investigated the effects of Irisin on dehydroepiandrosterone (DHEA)-induced PCOS in mice and evaluated the effect of Irisin on serum hormone levels and changes in body temperature, body weight, and ovarian morphology. In our study, we found that Irisin can enhance the thermogenesis and insulin sensitivity of PCOS mice by activating the function of BAT. In addition, Irisin treatment can correct the menstrual cycle of PCOS mice, improve the serum steroid hormone disorder status, and reduce the formation of ovarian cystic follicles. In conclusion, our results showed that Irisin treatment significantly improved the metabolic disorder of PCOS and may provide a new and alternative therapy for the treatment of this pathology.
Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Animais , Desidroepiandrosterona , Feminino , Fibronectinas , Humanos , Camundongos , Fenótipo , Síndrome do Ovário Policístico/metabolismoRESUMO
BACKGROUND: To report the multimodal imaging and treatment of fifteen retinal capillary hemangioblastomas (RCHs) associated with Von Hippel-Lindau syndrome in a monocular patient during a long-term following-up, which supply high-resolution exquisite SS-OCTA images (VG200; SVision Imaging, Ltd., Luoyang, China) and management experience about multiple RCHs. CASE PRESENTATION: A 34-year-old monocular male patient complained decreased visual acuity (20/100) without pain and redness in the left eye five years ago. Von Hippel-Lindau syndrome were diagnosed with genetic testing. He, his son and daughter all carried a heterozygosity missense variant c.499C > T (p. Arg167Trp) in the Hg19 gene, a VHL gene located in Chr3:10,191,506. Fifteen RCHs were identified by the application of multimodal imaging, which including fundus photo, fundus autofluorescence (FAF), B-scan ultrasonography (US), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) and swept-source optical coherence tomography angiography (SS-OCTA). Transscleral cryotherapy and laser photocoagulation were performed to destroy the largest RCH with the size of 4 PD in diameter. Laser photocoagulation was conducted to seal the middle or tiny RCHs (< 1.5 PD) and their nourishing vessels. The retinal edema and exudative macular detachment were successfully relieved by intraocular injection of bevacizumab for 5 times. The RCHs in the left eye responded well to these treatments and best corrected visual acuity was 20/25 for three years. Three-month recall visits were recommended for him. CONCLUSION: For multiple retinal capillary hemangioblastomas in monocular patients, precise combined therapy guided by multimodal imaging has a profound impact on the management of new and recurrent RCHs.
Assuntos
Hemangioblastoma , Neoplasias da Retina , Doença de von Hippel-Lindau , Adulto , Angiofluoresceinografia/métodos , Hemangioblastoma/complicações , Hemangioblastoma/diagnóstico , Humanos , Masculino , Imagem Multimodal , Neoplasias da Retina/complicações , Neoplasias da Retina/diagnóstico , Tomografia de Coerência Óptica/métodos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnósticoRESUMO
The INO80 complex, a SWI/SNF family chromatin remodeler, has regulatory effects on ESC self-renewal, somatic cell reprogramming and blastocyst development. However, the role of INO80 in regulating trophoblast cells and recurrent miscarriage (RM) remains elusive. To investigate the in vivo effects of Ino80 in embryo development, we disrupted Ino80 in C57 mice, which resulted in embryonic lethality. Silencing of Ino80 led to decreased survival capacity, migration and invasion of trophoblasts. Furthermore, RNA high-throughput sequencing (RNA-seq) revealed that Ino80 silencing closely resembled the gene expression changes in RM tissues. To investigate the mechanisms for these results, RNA-seq combined with high-throughput sequencing (ChIP-seq) was used in trophoblast cells, and it showed that Ino80 physically occupies promoter regions to affect the expression of invasion-associated genes. Last, Western blotting analyses and immunofluorescence staining revealed that the content of INO80 was reduced in RM patients compared to in healthy controls. This study indicates that INO80 has a specific regulatory effect on the viability, migration and invasion of trophoblast cells. Combined with its regulation of the expression of invasion-associated genes, it has been proposed that epigenetic regulation plays an important role in the occurrence of RM, potentially informing RM therapeutic strategies.
Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , Aborto Habitual/patologia , Movimento Celular , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética , Regulação da Expressão Gênica , Trofoblastos/patologia , ATPases Associadas a Diversas Atividades Celulares/genética , Aborto Habitual/etiologia , Aborto Habitual/metabolismo , Adulto , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , RNA-Seq , Transdução de Sinais , Trofoblastos/metabolismo , Adulto JovemRESUMO
BACKGROUND: With the broadened application of gene expression profiles analysis, the role of miRNA and circRNA are of increasing concern in recent years, especially during the pathogenesis of cancer. However, to date, the reported on this area in cervical cancer are limited. METHOD: In this study, Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis were utilized to screen out differentially expressed (DE) circular RNAs in cervical cancer, and then we predicted and screened the combined microRNAs (miRNA) and downstream mRNAs to construct circular (circ)RNA-miRNA-mRNA network. RESULT: As a result, a regulatory circular (circ)RNA-miRNA-mRNA with 1 circRNA node, 4 miRNA nodes, 135 mRNA nodes were constructed in an attempt to provide novel biomarkers for the pathogenesis of cervical cancer. In addition, enrichment analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on mRNAs in the network. After further screening of mRNAs by two online databases of GEPIA2 and RNAyhrid, precise target genes were obtained. Next, we screened out four target genes (CXCL16, IRF4, OAS3 and PTGER3) by constructing the protein-protein interaction (PPI) network, and mapped them to the initial network to reconstruct the circRNA-miRNA-mRNA network. Notably, the low expression of IRF4 was demonstrated to be associated with a significantly poorer overall survival in the GEPIA2 database, which was also verified by the immunofluorescence of the sections in Human Protein Atlas (HPA). The upstream miRNA corresponding to IRF4 is hsa-miR-1228-3p. CONCLUSION: From above concern, it can conclude that hsa_circ_0000301/hsa-miR-1228-3p/IRF4 may be involved in the occurrence and development of cervical cancer. However, the specific mechanism should be further studied and confirmed.
Assuntos
Biomarcadores Tumorais/metabolismo , Fatores Reguladores de Interferon/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Neoplasias do Colo do Útero/diagnóstico , Biologia Computacional , Conjuntos de Dados como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
WHAT IS KNOWN AND OBJECTIVE: In recent years, the resistance of Mycoplasma pneumoniae to macrolide antibiotics has increased significantly. The health systems are facing significant challenges in carrying out the diagnosis and treatment of refractory Mycoplasma pneumoniae pneumonia in children. Levofloxacin is suitable for treating infectious diseases in various systems but limited in children due to arthropathy issues in weight-bearing joints. This study aimed to evaluate the efficacy and safety of levofloxacin in children with macrolide-resistant Mycoplasma pneumoniae pneumonia. METHODS: We retrospectively enrolled six confirmed cases of refractory Mycoplasma pneumoniae pneumonia who were admitted in the paediatric respiratory ward of Shandong provincial hospital Affiliated to Shandong first Medical University between 1st January 2020 and 29th February 2020. Levofloxacin was given to the patients through the intravenous or oral route as per the following dosages :<5 years, 8-10 mg/kg q12 h; >5 years, 8-10 mg/kg, qd for 10 days. The clinical data were collected and analysed. RESULTS AND DISCUSSION: The average age of the enrolled cases was six years and nine months (range, four years, and seven months to eleven years and seven months). All cases were found to be drug-resistant and were treated with azithromycin combined with antibacterial drugs. Levofloxacin was used in the patient's refractory to macrolide antibiotics. The temperature of five cases returned to normal 1-2 days after treatment with levofloxacin, and the imaging of the four cases showed expected improvements. The gastrointestinal symptoms, neurological manifestations, joint symptoms, blood parameters, liver and kidney functions, and exercise conditions of the children were closely monitored. The follow-up time of the patients ranged from one week to five months. No drug-related adverse reactions were observed in patients during treatment or during follow-up. WHAT IS NEW AND CONCLUSION: The clinical symptoms and imaging significantly improved after treatment with levofloxacin, and no drug-related adverse reactions were observed. Levofloxacin proved to be an effective and safe drug in the treatment of children with macrolide-resistant mycoplasma pneumonia. This study will provide a reference for evaluating the efficacy and safety of levofloxacin in the paediatric population.
Assuntos
Antibacterianos/uso terapêutico , Levofloxacino/uso terapêutico , Macrolídeos/farmacologia , Pneumonia por Mycoplasma/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Feminino , Humanos , Levofloxacino/efeitos adversos , Levofloxacino/farmacologia , Masculino , Estudos RetrospectivosRESUMO
The atomically dispersed metal is expected as one of the most promising Fenton-like catalysts for the degradation of recalcitrant organic pollutants (ROPs) by the strong "electronic metal-support interactions" (EMSIs). Here, we develop an atomically dispersed metal-atom alloy made by guest Au atoms substitute host V atoms in the two-dimensional VO2 (B) nanobelt support (Au/VO2 ) to activate Fenton-like oxidation for elimination of ROPs. The 2D nanobelt structure enlarges the exposure of atomically Au thus increasing the number of active sites to absorb more S2 O8 2- ions. And the EMSIs regulate the charge density in Au atoms to present positive charge Au+ , lowering the energy barrier of S2 O8 2- decomposition to produce SO4 .- . The Au/VO2 catalyst possesses excellent durable and reliable characteristics and exhibits record-breaking efficiency with TOF as high as 21.42â min-1 , 16.19â min-1 , and 80.89â min-1 for rhodamine, phenol, and bisphenolâ A degradation, respectively.
RESUMO
Insufficient trophoblast invasion is the key factor for the occurrence of recurrent spontaneous abortions (RSA). Our previous studies identified Yin Yang 1 (YY1) as a transcription factor involved in the regulation of trophoblast invasiveness at the maternal-fetal interface. Long noncoding RNAs (lncRNAs) can regulate gene expression and autophagy in many ways. The purpose of this study was to explore the relationship between YY1 and lncRNAs and the mechanism by which lncRNAs affect the biological behavior of trophoblasts. Bioinformatic analysis predicted that YY1 had three binding sites in the plasmacytoma variant translocation 1 (PVT1) promoter region. Chromatin immunoprecipitation experiments and electrophoretic mobility shift assays verified that YY1 can directly bind to the PVT1 promoter. Compared with its expression levels in human placental villi tissue samples from the normal pregnancy group, the PVT1 expression levels were significantly lower in tissues from the RSA group. PVT1 knockdown significantly reduced adhesion, invasion, autophagy, and mTOR expression in HTR-8/SVneo cells and greatly increased apoptosis in vitro. This study revealed a novel regulatory pathway in which YY1 can act directly on PVT1 promoter to regulate its transcription, which further affects trophoblast invasion and adhesion by regulating autophagy via the mTOR pathway, and these effects might be involved in RSA pathogenesis.
Assuntos
Autofagia/genética , Adesão Celular/genética , RNA Longo não Codificante/genética , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/genética , Trofoblastos/fisiologia , Fator de Transcrição YY1/genética , Aborto Habitual/genética , Adulto , Apoptose/genética , Autofagia/fisiologia , Adesão Celular/fisiologia , Linhagem Celular , Movimento Celular/genética , Feminino , Regulação da Expressão Gênica/genética , Humanos , Gravidez , Regiões Promotoras Genéticas/genética , Transcrição Gênica/genética , Adulto JovemRESUMO
In this study, we attempted to evaluate the prognostic value of infiltrating immune/stromal cells in clear cell renal cell carcinoma (ccRCC), by using the immune scores and stromal scores based on the "Estimation of STromal and Immune cells in MAlignant Tumours using Expression data" algorithm to represent the levels of infiltrating immune cells and stromal cells. We found that the infiltrating immune cells were associated with poor prognosis of ccRCC. To assess the role of infiltrating immune cells in ccRCC cells, first, we performed differentially expressed genes analysis and functional analysis for validation. The results showed that the underlying mechanism by which infiltrating immune cells promoted cancer progression involved in regulating the nuclear division, angiogenesis, and immune response. Next, we investigated the relationship between infiltrating immune cells and mutations in ccRCC cells. We found that the infiltrating immune cells have certain effects on genetic mutations. In conclusion, infiltrating immune cells within the tumor microenvironment can be used to predict prognosis in ccRCC.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Linfócitos do Interstício Tumoral/imunologia , Mutação , Microambiente Tumoral/imunologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA4) inhibitors have been shown to significantly prolong the overall survival (OS) in a wide range of cancers. However, its application in clear cell renal cell carcinoma (ccRCC) is limited due to the therapy response, and the prognostic value of CTLA4 in ccRCC has not been investigated in detail. Methods: By using immunohistochemistry, Kaplan-Meier (K-M) analysis, uni- and multi-variate Cox analysis, we comprehensively and systematically studied the prognostic value of CTLA4 in ccRCC. Then, we applied Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and CIBERSORT, ESTIMATE algorithm, ssGSEA and somatic mutation analyses to reveal the impact of CTLA4 on the landscape of tumor-infiltrating lymphocytes (TILs) infiltration and genetic mutation. Besides, given current concerns caused by combined immunotherapy, we also investigated the relationship between CTLA4 and other immune checkpoints. Results: In vitro experiment and data mining showed that, CTLA4 was up-regulated in ccRCC tissues and closely related to the disease progression as well as a poor prognosis. Deeper researches demonstrated that CTLA4 regulates T cell activation and was significantly linked to TIL-abundant tumor microenvironment (TME), but was accompanied by an immunosuppressed phenotype. Mutation analysis showed that CTLA4 was associated with more frequent BRCA-associated protein 1 (BAP1) mutation. Moreover, we found that CTLA4 was markedly correlated with multiple immune checkpoints, which suggested that ccRCC patients with high expressed CTLA4 may benefit more from immune checkpoint blockades (ICBs) combined therapy. Conclusion: CTLA4 has a profound impact on the landscape of TILs and genetic mutation, and can be used as the biomarker with high prognosis value in ccRCC.
RESUMO
PURPOSE: To investigate the relationship between posterior staphyloma and dome-shaped macula (DSM) in highly myopic eyes. METHODS: The clinical data were collected from patients with high myopia: diopter, best-corrected visual acuity, axial length, fundus images, optical coherence tomography, and 3D magnetic resonance imaging. A DSM was defined as a convex curvature of the macula in one or both of the vertical and horizontal optical coherence tomography scans. The relationship between DSM and posterior staphyloma was evaluated. RESULTS: A total of 123 eyes were included. Dome-shaped macula was found in 18 eyes (14.63%). Twelve eyes with DSM had positive 3D magnetic resonance imaging findings. Nine eyes had horizontal oval-shaped dome, and a band-shaped inward convexity that extended horizontally from the optic disc through the fovea could be seen. Three eyes had round dome, and 3D magnetic resonance imaging showed a round inward convexity of the macular area. Five inward convexities were the border of multiple staphylomas, five were the boundary of one staphyloma, and two were within a single staphyloma. CONCLUSION: The formation of highly myopic DSM is related to the morphological change of the entire posterior segment.
Assuntos
Macula Lutea/diagnóstico por imagem , Miopia Degenerativa/complicações , Segmento Posterior do Olho/diagnóstico por imagem , Doenças Retinianas/diagnóstico por imagem , Doenças da Esclera/diagnóstico por imagem , Adulto , Idoso , Comprimento Axial do Olho/patologia , Dilatação Patológica , Feminino , Humanos , Macula Lutea/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Segmento Posterior do Olho/patologia , Doenças Retinianas/etiologia , Doenças da Esclera/etiologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologiaRESUMO
OBJECTIVES: The purpose of this study was to compare the rate of preterm birth, low birth weight, and foetal growth restriction in assisted reproductive technology (ART) singleton pregnancies diagnosed with vanishing twin (VT) syndrome to those of ART pregnancies that were originally singleton pregnancies. METHODS: In this retrospective study, 177 pregnancies diagnosed with VT syndrome were matched and compared with 218 primary singleton pregnancies. The preterm birth and low birth weight rates of these two groups were evaluated. All pregnancies were conceived through ART and delivered at Peking University First Hospital and Hebei Xingtai Infertility Hospital from 2014 to 2016. RESULTS: The preterm delivery rate (20.90 vs. 8.72%, p<0.05) was significantly higher in the ART singletons with VT syndrome than in the control singleton group. The proportion of low-birth-weight (<2500 g) infants was also higher in the VT group than in the primary singleton group (10.73 vs. 3.67%, p<0.05). In addition, the preterm birth rate of the naturally conceived singletons was significantly lower than that of the ART singletons (6.00 vs. 14.18%, p<0.05). CONCLUSIONS: ART singleton pregnancies with VT syndrome have higher rates of preterm birth and low-birth-weight new-borns than ART pregnancies that were originally singleton pregnancies.