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A growing body of research documents that the use of pornography is becoming more frequent among male sexual minorities. According to the sexual script acquisition, activation, application model of mediated sexual socialization (3AM), pornography can be considered a potential factor influencing an individual's partner preference. In addition, perceived realism could moderate the link between pornography consumption and partner preferences. This study explored the relationship between pornographic video consumption and partner preference among male sexual minorities and the moderating role of perceived realism. A total of 595 male sexual minorities aged 18 to 47 years (M = 21.70, SD = 3.83), including 82.9% gay men and 17.1% bisexual men, were enrolled in the study. Our results revealed the following: (1) The frequency of pornographic video consumption and male sexual minorities' preferences for appearance and sexual ability in partner selection were positively correlated (r = .06/.07, ps < .05). (2) When perceived realism was low, pornographic video consumption was not significantly associated with appearance and sexual ability preference. (3) Conversely, when perceived realism was high, pornographic video consumption was positively associated with appearance and sexual ability preference (ß = .17/.16, ps < .01). Findings highlight the mechanisms behind pornographic video consumption and partner preference in sexual minority males.
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Literatura Erótica , Parejas Sexuales , Minorías Sexuales y de Género , Humanos , Masculino , Adulto , Parejas Sexuales/psicología , Minorías Sexuales y de Género/psicología , Persona de Mediana Edad , Literatura Erótica/psicología , Adolescente , Adulto Joven , Conducta Sexual/psicología , China , Homosexualidad Masculina/psicología , Pueblos del Este de AsiaRESUMEN
MicroRNAs (miRNAs) are noncoding RNAs with 18-26 nucleotides; they pair with target mRNAs to regulate gene expression and produce significant changes in various physiological and pathological processes. In recent years, the interaction between miRNAs and their target genes has become one of the mainstream directions for drug development. As a large-scale biological database that mainly provides miRNA-target interactions (MTIs) verified by biological experiments, miRTarBase has undergone five revisions and enhancements. The database has accumulated >2 200 449 verified MTIs from 13 389 manually curated articles and CLIP-seq data. An optimized scoring system is adopted to enhance this update's critical recognition of MTI-related articles and corresponding disease information. In addition, single-nucleotide polymorphisms and disease-related variants related to the binding efficiency of miRNA and target were characterized in miRNAs and gene 3' untranslated regions. miRNA expression profiles across extracellular vesicles, blood and different tissues, including exosomal miRNAs and tissue-specific miRNAs, were integrated to explore miRNA functions and biomarkers. For the user interface, we have classified attributes, including RNA expression, specific interaction, protein expression and biological function, for various validation experiments related to the role of miRNA. We also used seed sequence information to evaluate the binding sites of miRNA. In summary, these enhancements render miRTarBase as one of the most research-amicable MTI databases that contain comprehensive and experimentally verified annotations. The newly updated version of miRTarBase is now available at https://miRTarBase.cuhk.edu.cn/.
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Regiones no Traducidas 3' , Bases de Datos de Ácidos Nucleicos , Redes Reguladoras de Genes , MicroARNs/genética , Neoplasias/genética , ARN no Traducido/genética , Animales , Sitios de Unión , Biomarcadores/metabolismo , Minería de Datos/estadística & datos numéricos , Exosomas/química , Exosomas/metabolismo , Regulación de la Expresión Génica , Humanos , Internet , Ratones , MicroARNs/clasificación , MicroARNs/metabolismo , Anotación de Secuencia Molecular , Neoplasias/metabolismo , Neoplasias/patología , Polimorfismo de Nucleótido Simple , ARN no Traducido/clasificación , ARN no Traducido/metabolismo , Células Tumorales Cultivadas , Interfaz Usuario-ComputadorRESUMEN
Time-series experiments are crucial for understanding the transient and dynamic nature of biological phenomena. These experiments, leveraging advanced classification and clustering algorithms, allow for a deep dive into the cellular processes. However, while these approaches effectively identify patterns and trends within data, they often need to improve in elucidating the causal mechanisms behind these changes. Building on this foundation, our study introduces a novel algorithm for temporal causal signaling modeling, integrating established knowledge networks with sequential gene expression data to elucidate signal transduction pathways over time. Focusing on Escherichia coli's (E. coli) aerobic to anaerobic transition (AAT), this research marks a significant leap in understanding the organism's metabolic shifts. By applying our algorithm to a comprehensive E. coli regulatory network and a time-series microarray dataset, we constructed the cross-time point core signaling and regulatory processes of E. coli's AAT. Through gene expression analysis, we validated the primary regulatory interactions governing this process. We identified a novel regulatory scheme wherein environmentally responsive genes, soxR and oxyR, activate fur, modulating the nitrogen metabolism regulators fnr and nac. This regulatory cascade controls the stress regulators ompR and lrhA, ultimately affecting the cell motility gene flhD, unveiling a novel regulatory axis that elucidates the complex regulatory dynamics during the AAT process. Our approach, merging empirical data with prior knowledge, represents a significant advance in modeling cellular signaling processes, offering a deeper understanding of microbial physiology and its applications in biotechnology.
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Algoritmos , Proteínas de Escherichia coli , Escherichia coli , Regulación Bacteriana de la Expresión Génica , Redes Reguladoras de Genes , Escherichia coli/genética , Escherichia coli/metabolismo , Anaerobiosis/genética , Aerobiosis , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Transducción de Señal/genética , Modelos Biológicos , Perfilación de la Expresión Génica/métodosRESUMEN
DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/â¼MethHC.
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Biomarcadores de Tumor/genética , Metilación de ADN , Bases de Datos Genéticas , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias/genética , Biomarcadores de Tumor/metabolismo , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Variaciones en el Número de Copia de ADN , Progresión de la Enfermedad , Elementos de Facilitación Genéticos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Internet , Análisis por Micromatrices , Anotación de Secuencia Molecular , Mutación , Neoplasias/clasificación , Neoplasias/diagnóstico , Neoplasias/metabolismo , Programas Informáticos , TranscriptomaRESUMEN
MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.
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Bases de Datos de Ácidos Nucleicos , MicroARNs/metabolismo , MicroARN Circulante/metabolismo , Minería de Datos , Regulación de la Expresión Génica , ARN Mensajero/metabolismo , Interfaz Usuario-ComputadorRESUMEN
Relatively few studies investigating plant diseases in blue honeysuckle (Lonicera caerulea L.) have been conducted in China. In September 2021, a leaf spot disease was observed on approximately 10% of blue honeysuckle 'Lanjingling' leaves in a 0.02 ha field plantation in Tiekuang Street (124.36°E, 40.12°N) in Dandong City, Liaoning Province, China. The main symptom consisted of leaf spots with black mildew centers typically surrounded by yellow halos. Small pieces (3-4 mm) of the infected leaves were plated onto potato dextrose agar (PDA) medium as described by Wang et al. (2020) and six purified cultures were obtained through single spore culture on PDA. The observed conidia, consistent with the morphology of Alternaria alternata, were obpyriform and dark brown, measuring 5.8 to 15.3 µm × 7.9 to 42.5 µm, with 1-6 transverse septa and 0-3 longitudinal septa (n = 50) (Simmons 2007). For molecular verification, genomic DNA was extracted from a representative isolate LD-8. The ITS (GenBank OL454815), GPD (GenBank OL601993), TEF (GenBank OL538256), RPB2 (GenBank OL601966), and Alt (GenBank OL538257) genes were partially amplified with the respective primers ITS1/ITS4 (White et al. 1990), GPD1/GPD2 (Woudenberg et al. 2015), EFl-728F/EFI-986R (Carbone and Kohn 1999), RPB2-5F2/RPB2-7CR (Liu et al. 1999), and Alt-for/Alt-rev (Hong et al. 2005). BLAST analysis revealed that these genes shared 99%-100% identity with OK345332, MK451977, MN756011, KU933459, and MN655781, respectively. A greenhouse experiment was conducted using six, healthy two-year-old blue honeysuckle 'Lanjingling' plants to observe disease development (Mirzwa-Mróz et al. 2018). After 10 d, we noted typical leaf spot symptoms on inoculated leaves sprayed with a conidial suspension (106 spores/mL) while no symptoms were detected on uninoculated leaves. The same isolate, reisolated from infected leaves with the same morphological and molecular traits, was also identified as A. alternata, confirming Koch's postulates. The fungus was previously reported in cockscomb plants in Heilongjiang Province, China (Wang et al. 2020). To our knowledge, this is the first report of leaf spot disease caused by A. alternata in blue honeysuckle grown in China. This study will provide a basis for future development of effective protection strategies against blue honeysuckle leaf spot in China.
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BACKGROUND: Benign splenic lesions are rarely encountered. This study aimed to review the clinical characteristics and surgical outcomes in a case series of 30 pediatric patients. METHODS: From January 1st, 2001 to December 31st, 2021, 30 pediatric patients from a single center were consecutively included. Electronic medical records were reviewed and patients were followed up. Clinical presentations, imaging features, surgical procedures, pathological diagnoses, and prognoses were summarized. The lesion locations and 7-day postoperative platelet levels were compared between total and partial splenectomy patients. RESULTS: Eighteen males and twelve females were included, with mean age at surgery 116.4 ± 43.6 months. The clinical presentations included abdominal pain (16/30), splenomegaly (6/30), skin petechia (2/30), hemolytic jaundice (1/30), and no symptoms (5/30). Pathological diagnoses included congenital epithelial cyst (CEC, 17/30), vascular malformation (8/30), sclerosing angiomatoid nodular transformation (SANT, 3/30), hamartoma (1/30), and leiomyoma (1/30). Patients undergone total splenectomy were more likely to have a lesion involving the hilum than those undergone partial splenectomy (68.4% vs 31.6%, P = 0.021). The 7-day postoperative platelet level was higher in total splenectomy patients than partial splenectomy patients (adjusted means 694.4 × 109/L vs 402.4 × 109/L, P = 0.002). CONCLUSIONS: Various clinical characteristics of pediatric benign splenic lesions are summarized. The most common pathological diagnoses are congenital epithelial cyst and vascular malformation. Partial and total splenectomy result in good prognosis with a low recurrence rate, and the former is preferred to preserve splenic function if possible.
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Quistes , Enfermedades del Bazo , Malformaciones Vasculares , Niño , Femenino , Humanos , Masculino , Esplenectomía/métodos , Enfermedades del Bazo/cirugíaRESUMEN
Carbonic anhydrase IX (CA9), a pH-regulating transmembrane protein, is highly expressed in solid tumors, and particularly in clear cell renal cell carcinoma (ccRCC). The catalytic mechanisms of CA9 are well defined, but its roles in mediating cell migration/invasion and survival in ccRCC remain to be determined. Here, we confirmed that the mRNA expression of CA9 in ccRCC was significantly higher than that in para-carcinoma tissues from analysis of the datasets in The Cancer Genome Atlas. CA9 knockdown upregulated oxidative phosphorylation-associated proteins and increased mitochondrial biogenesis, resulting in the reversal of the Warburg phenotype and the inhibition of cell growth. Our study revealed that CA9 knockdown upregulated mitochondrial arginase 2 (ARG2), leading to the accumulation of putrescine, which suppressed ccRCC proliferation. Surfaceomics analysis revealed that CA9 knockdown downregulated proteins associated with extracellular matrix (ECM)-receptor interaction and cell adhesion, resulting in decreased cell migration. CA9 silencing also downregulated amino acid transporters, leading to reduced cellular amino acids. Collectively, our data show that CA9 knockdown suppresses proliferation via metabolic reprogramming and reduced cell migration, reaffirming that CA9 is a potential therapeutic target for ccRCC treatment.
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Antígenos de Neoplasias/metabolismo , Anhidrasa Carbónica IX/metabolismo , Carcinoma de Células Renales/metabolismo , Movimiento Celular , Neoplasias Renales/metabolismo , Biogénesis de Organelos , Putrescina/metabolismo , Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Antígenos de Neoplasias/genética , Arginasa/genética , Arginasa/metabolismo , Anhidrasa Carbónica IX/genética , Línea Celular Tumoral , Proliferación Celular , Silenciador del Gen , Células HEK293 , Humanos , Proteoma/genética , Proteoma/metabolismo , Putrescina/toxicidad , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Efecto Warburg en OncologíaRESUMEN
Previous studies have indicated homogamy in partner preferences among gay and bisexual men. Individuals on Blued (the most popular gay dating app in China) could identify their body type and preferred physiques according to six categories: monkey (thin gay men), average, muscularity, bear (heavy and hairy gay men), baboon (smaller than bears), and pig (plumper than bears). This study examined patterns of physique preferences across body types as well as sexual self-labels (tops, bottoms, versatiles, and others). In total, 188,716 Blued profiles (Mage = 31.1, SD = 7.1) were obtained. Multiple group latent class analysis was used to examine the patterns of physique preferences across the body type groups. The results revealed seven classes of physique preference. The four common physique preferences shared by all body type groups were "like averages," "like monkeys," "like muscularity," and "like bears." Individuals with a monkey or average body type exhibited a specific pattern of physique preference: "dislike bears." The two physique preferences specific to gay bear men were "like averages and muscularity," and "dislike monkeys." The highest preference for each physique was observed among individuals of the same body type. Furthermore, tops were more likely to have a muscular body and prefer a monkey physique, whereas bottoms were more likely to have a monkey body and prefer a muscular physique. These findings indicate body type-specific physique preferences based on an individual's own body type and sexual self-label identification, thus partially supporting the concept of homogamy in the physique preferences of gay men.
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INTRODUCTION AND IMPORTANCE: Congenital hepatoblastoma is an exceedingly rare neoplasm, predominantly documented as isolated instances, with contentious aspects surrounding its therapeutic approaches and prognostic implications. This study aims to comprehensively summarize and evaluate the management experience of congenital hepatoblastoma (CHB). CASE PRESENTATION: This cohort comprised five infants diagnosed with hepatoblastoma, confirmed through pathological examination, and with an onset of symptoms before 28 days of age. They were enrolled between November 2019 and May 2022. The treatment course they underwent has been summarized, and their prognosis has been subject to analysis. CLINICAL DISCUSSION: Distinguishing congenital hepatoblastoma from other medical conditions is typically necessary. Given the patient's tender age, the approach to treatment demands comprehensive assessment, particularly in cases involving unique tumor locations or substantial tumor sizes. The selection of treatment modalities, encompassing preoperative neoadjuvant chemotherapy and surgical techniques, becomes of paramount importance. Furthermore, determining the treatment's endpoint poses a notable challenge and often necessitates a comprehensive evaluation. CONCLUSION: For pediatric patients afflicted with CHB, the application of preoperative neoadjuvant chemotherapy mitigates surgical risks, while the incorporation of surgical procedures followed by postoperative chemotherapy significantly enhances the overall prognosis. Additionally, AFP-L3% levels may serve as a valuable adjunctive marker signifying the conclusion of treatment.
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HYPOTHESIS: Elucidation of the micro-mechanisms of sol-gel transition of gelling glucans with different glycosidic linkages is crucial for understanding their structure-property relationship and for various applications. Glucans with distinct molecular chain structures exhibit unique gelation behaviors. The disparate gelation phenomena observed in two methylated glucans, methylated (1,3)-ß-d-glucan of curdlan (MECD) and methylated (1,4)-ß-d-glucan of cellulose (MC), notwithstanding their equivalent degrees of substitution, are intricately linked to their unique molecular architectures and interactions between glucan and water. EXPERIMENTS: Density functional theory and molecular dynamics simulations focused on the electronic property distinctions between MECD and MC, alongside conformational variations during thermal gelation. Inline attenuated total reflection Fourier transform infrared spectroscopy tracked secondary structure alterations in MECD and MC. To corroborate the simulation results, additional analyses including circular dichroism, rheology, and micro-differential scanning calorimetry were performed. FINDINGS: Despite having similar thermally induced gel networks, MECD and MC display distinct physical gelation patterns and molecular-level conformational changes during gelation. The network of MC gel was formed via a "coil-to-ring" transition, followed by ring stacking. In contrast, the MECD gel comprised compact irregular helices accompanied by notable volume shrinkage. These variations in gelation behavior are ascribed to heightened hydrophobic interactions and diminished hydrogen bonding in both systems upon heating, resulting in gelation. These findings provide valuable insights into the microstructural changes during gelation and the thermo-gelation mechanisms of structurally similar polysaccharides.
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Geles , Simulación de Dinámica Molecular , Geles/química , Metilación , Temperatura , beta-Glucanos/química , Glicósidos/química , Teoría Funcional de la Densidad , Glucanos/química , Celulosa/químicaRESUMEN
Objectives: This study aimed to investigate the association between contrast-enhanced ultrasound-detected (CEUS) perfusion patterns of carotid plaque and the occurrence of stroke. Materials and methods: This prospective observational study finally enrolled 256 patients (151 of them having undergone CEUS) from 7851 patients who underwent carotid artery ultrasound from May 2019 to December 2019 with the endpoint being the occurrence of stroke. The risk factors and carotid ultrasound fetures was obtained from those patients. Analyze the relationship between these variables and stoke occurrence. Results: Patients in the recurrent stroke group and those in the no-recurrent stroke group were statistically different in stenosis rate, plaque echo, fibrous cap integrity, calcification of fibrous cap, hypoechoic area within the plaque, and the pattern of neovascularization perfusion from plaque surface to plaque interior (P < 0.05). Upon adjusting for variables, in all subjects, Cox regression analysis showed that symptoms experienced within the past 6 months (RR = 2.486, 95 % CI: 1.282-4.821), moderate-to-severe carotid stenosis (RR = 2.407, 95 % CI: 1.480-4.593), calcification of fibrous cap (RR = 1.599, 95 % CI: 0.727-3.516) and patchy hypoechoic areas within plaque (RR = 2.486, 95 % CI: 1.107-5.578)independently predicted stroke occurrence across all subjects.; Among subjects underwent CEUS, Cox regression analysis demonstrated that moderate-to-severe carotid artery stenosis (RR = 2.105, 95 % CI: 1.425-4.510) and microbubbles entering the interior of the plaque from its surface (RR = 2.323, 95 % CI: 1.175-4. 594) were independent predictors of stroke occurrence. Conclusions: The neovascularization perfusion pattern from the plaque surface to its interior serves as an independent predictor of stroke occurrence, thereby potentially enhancing clinical decision-making.
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Objective:To investigate long-term auditory changes and characteristics of Alport syndromeï¼ASï¼ patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33ï¼25 males, 8 females, aged 3.4-27.8 yearsï¼ were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal diseaseï¼ESRDï¼, predominantly males ï¼6/7ï¼. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD groupï¼P=0.013ï¼. There was no correlation between the progression of renal disease and long-term hearing levelï¼P>0.05ï¼. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing lossï¼P=0.048ï¼, and there was no correlation with the severity of hearing lossï¼P>0.05ï¼. Among 11 cases, theCOL4A5mutationwas most common ï¼8 out of 11ï¼, but there was no significant correlation between the mutation type and hearing phenotypeï¼P>0.05ï¼. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
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Sordera , Pérdida Auditiva , Fallo Renal Crónico , Nefritis Hereditaria , Masculino , Niño , Femenino , Humanos , Nefritis Hereditaria/genética , Nefritis Hereditaria/patología , Estudios Retrospectivos , Riñón , Pérdida Auditiva/genética , Fallo Renal Crónico/genética , Fallo Renal Crónico/patología , MutaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae Flavescentis Radix (Kushen) is the primary herb component of Compound Kushen Injection (CKI), an approved clinical treatment for tumors. Despite CKI's widespread use, the underlying mechanisms of Kushen regarding microRNA-target and pathway remain unclear in non-small cell lung cancer (NSCLC). AIM OF THE STUDY: This study aimed to elucidate the crucial miRNAs-targets and pathways responsible for the Kushen's impact on NSCLC. MATERIALS AND METHODS: CCK8, colony formation, and apoptosis assays were performed to assess the effects of Kushen on NSCLC cells. Subsequently, we treated the A549 cell line with varying concentrations of Kushen to obtain mRNA and miRNA expression profiles. A DE (differentially expressed) miRNAs-DEGs network was then constructed to identify the critical miRNA-mRNA interaction influenced by Kushen. Furthermore, we performed clinical significance and prognosis analyses of hub genes to narrow down key genes and their corresponding miRNAs. Finally, the effects of Kushen on critical miRNA-mRNA interaction and related pathway were verified by in vitro and in vivo experiments. RESULTS: In this study, we initially demonstrated that Kushen significantly inhibited cell proliferation, suppressed colony formation, and induced apoptosis in the A549 cells, PC9 cells, and the A549 zebrafish xenograft model. Through expression profile analysis, a DE miRs-DEGs network was constructed with 16 DE miRs and 68 DEGs. Through the network analysis and expression validation, we found Kushen could significantly down-regulate miR-183-5p expression and up-regulate EGR1 expression. Additionally, Kushen affected the PTEN/Akt pathway, increasing PTEN expression and decreasing pAkt expression. Finally, matrine, the essential active compound of Kushen, also inhibited cell growth, induced apoptosis, and regulated miR-183-5p/EGR1 and PTEN/AKT pathway. CONCLUSIONS: Altogether, these findings supported the critical role of miR-183-5p/EGR1 and the PTEN/AKT pathway in the beneficial effects of Kushen on NSCLC, highlighting the therapeutic potential of Kushen in NSCLC treatment.
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Productos Biológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Animales , MicroARNs/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas Proto-Oncogénicas c-akt , Pez Cebra , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genéticaRESUMEN
Sepsis-associated acute kidney injury (SA-AKI) is a severe and life-threatening condition with high morbidity and mortality among emergency patients, and it poses a significant risk of chronic renal failure. Clinical treatments for SA-AKI remain reactive and non-specific, lacking effective diagnostic biomarkers or treatment targets. In this study, we established an SA-AKI mouse model using lipopolysaccharide (LPS) and performed proteomics and metabolomics analyses. A variety of bioinformatic analyses, including gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), protein and protein interactions (PPI), and MetaboAnalyst analysis, were conducted to investigate the key molecules of SA-AKI. Integrated proteomics and metabolomics analysis revealed that sepsis led to impaired renal mitochondrial function and metabolic disorders. Immune-related pathways were found to be activated in kidneys upon septic infection. The catabolic products of polyamines accumulated in septic kidneys. Overall, our integrated analysis provides a multidimensional understanding of SA-AKI and identifies potential pathways for this condition.
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Background: Allergic rhinitis (AR) is a common nasal inflammatory disorder that severely affects an individual's quality of life (QoL) and poses a heavy financial burden. In addition to routine treatments, probiotic intervention has emerged as a promising strategy for preventing and alleviating allergic diseases. The main objective of this study was to determine the effect of a novel multi-strain probiotic mixture on AR symptoms and investigate potential targets underlying the probiotic intervention. Methods: A randomized, double-blind, placebo-controlled clinical study was conducted on AR patients who were allergic to autumnal pollens (n = 31). Placebo or a novel probiotic mixture, composed of Lactobacillus rhamnosus (L. rhamnosus) HN001, L. acidophilus NCFM, Bifidobacterium lactis (B. lactis) Bi-07, L. paracasei LPC-37, and L. reuteri LE16, was administered after 2 months. The therapeutic efficacy was evaluated by a symptom assessment scale. Before and during the pollen season, blood samples were collected, and peripheral blood mononuclear cells (PBMCs) were isolated for further tandem mass tags (TMTs)-based quantitative proteomic analyses. Potential targets and underlying pathological pathways were explored using bioinformatics methods. Results: During the pollen season, the rhinoconjunctivitis symptom score of participants who were administered probiotics (probiotic group, n = 15) was significantly lower than those administered placebo (placebo group, n = 15) (P = 0.037). The proteomic analyses identified 60 differentially expressed proteins (DEPs) in the placebo group, and subsequent enrichment analyses enriched a series of pathways and biological processes, including signaling pathways of inflammation, coagulation cascade, lipid, carbohydrate and amino acid metabolic pathways, and transcription and translation processes. Least Absolute Shrinkage and Selection Operator (LASSO) regression extracted five main elements, namely, GSTO1, ATP2A2, MCM7, PROS1, and TRIM58, as signature proteins. A total of 17 DEPs were identified in the probiotic group, and there was no pathway enriched. Comparison of DEPs in the two groups revealed that the expression levels of the high-mobility group nucleosome-binding domain-containing protein 2 (HMGN2) and Histone H1.2 presented an opposite trend with different interventions. Conclusion: Our data showed that AR symptoms alleviated after treatment with the novel multi-strain probiotic mixture, and the proteomic analyses suggested that HMGN2 and Histone H1.2 might be targets of probiotic intervention for seasonal AR.
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Renal tubular epithelial cells are one of the high energy-consuming cell types, which mainly depend on mitochondrial energy supply. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that is involved in alcohol metabolism and mitochondrial oxidative ATP production; however, its function in mitochondrial homoeostasis in acute kidney injury (AKI) is unclear. Here, we found that ALDH2 expression was predominantly decreased in cisplatin or maleic acid (MA) models both in vivo and in vitro. ALDH2 knockout (KO) mice exhibited exacerbated kidney impairment and apoptosis of tubular epithelial cells after cisplatin injection. In contrast, ALDH2 activation alleviated AKI and tubular cell apoptosis in both cisplatin- and MA-induced models. RNA sequencing revealed that the oxidative phosphorylation pathway was positively enriched in the renal tissues after Alda-1 pre-treatment in MA-induced mice. ALDH2 activation restored mitochondrial structure, mitochondrial membrane potential, and respiration rate, but downregulated glycolysis in MA-induced mice and human renal proximal tubular epithelial (HK-2) cells. Mechanistically, co-immunoprecipitation assays revealed that ALDH2 interacts with peroxisomal proliferator-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis, and advanced its nuclear translocation. Subsequently, PGC-1α knockdown almost abolished the improvement of ALDH2 activation on MA-induced tubular epithelial cells damage. Thus, our study revealed that ALDH2 activation alleviated mitochondrial dysfunction in AKI by enhancing PGC-1α-mediated mitochondrial biogenesis. Hence, ALDH2 may act as a potential therapeutic target to prevent AKI progression.
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Lesión Renal Aguda , Cisplatino , Animales , Humanos , Ratones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Aldehído Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa Mitocondrial/genética , Aldehído Deshidrogenasa Mitocondrial/metabolismo , Cisplatino/efectos adversos , Riñón/metabolismo , Ratones Noqueados , Mitocondrias/metabolismo , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismoRESUMEN
BACKGROUND: The typical imaging findings of hairy polyps have been described mostly in case reports. This study was conducted to describe the CT and MRI features of hairy polyps and their common associated abnormalities. METHODS: Medical records of 14 patients with pathological diagnosis of hairy polyps were collected for this study. For each patient, the medical records, including demographics, clinical manifestations, and imaging findings were reviewed. RESULTS: The female-to-male ratio was 3.7:1. The age at first episode varied from birth to 2.7 years. The masses were derived from the back side of the soft palate in seven (50.0%) cases, from the lateral pharyngeal wall in four (28.6%) cases, from the soft palate in one (7.1%) case, from the nasal vestibule in one (7.1%) case, and from the parapharyngeal space in one (7.1%) case. A total of 11 (78.6%) cases presented with pedicled masses containing fat and a central core of soft tissue, there were 3 (21.4%) cases whose imaging findings were atypical, and there were 6 (42.9%) patients who had other pathologies. CONCLUSIONS: Hairy polyps typically presented as pedicled masses containing fat and a central core of soft tissue, but sometimes their imaging findings can be atypical and they can be associated with other congenital abnormalities. CT and MRI are reliable methods for the diagnosis of hairy polyps and their associated abnormalities.
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Schistosomiasis, the second largest parasitic disease in the world after malaria, poses a significant threat to human health and causes public health issues. The disease primarily affects populations in economically underdeveloped tropical regions, earning it the title of "neglected tropical disease". Schistosomiasis is difficult to eradicate globally if medication alone is used. One of the essential elements of thorough schistosomiasis prevention and control is the management and disruption of the life cycle of intermediate host snails. The key approach to controlling the transmission of schistosomiasis is to control the intermediate hosts of the schistosome to disrupt its life cycle. We believe that approaching it from the perspective of the intermediate host's immunity could be an environmentally friendly and potentially effective method. Currently, globally significant intermediate host snails for schistosomes include Oncomelania hupensis, Biomphalaria glabrata, and Bulinus truncatus. The immune interaction research between B. glabrata and Schistosoma mansoni has a history of several decades, and the complete genome sequencing of both B. glabrata and B. truncatus has been accomplished. We have summarized the immune-related factors and research progress primarily studied in B. glabrata and B. truncatus and compared them with several humoral immune factors that O. hupensis research focuses on: macrophage migration inhibitory factor (MIF), Toll-like receptors (TLRs), and thioredoxin (Trx). We believe that continued exploration of the immune interactions between O. hupensis and Schistosoma japonicum is valuable. This comparative analysis can provide some direction and clues for further in-depth research. Comparative immunological studies between them not only expand our understanding of the immune defense responses of snails that act as intermediaries for schistosomes but also facilitate the development of more comprehensive and integrated strategies for schistosomiasis prevention and control. Furthermore, it offers an excellent opportunity to study the immune system of gastropods and their co-evolution with pathogenic organisms.
Asunto(s)
Biomphalaria , Schistosoma japonicum , Esquistosomiasis , Animales , Humanos , Schistosoma japonicum/genética , Esquistosomiasis/parasitología , Biomphalaria/parasitología , Bulinus , Schistosoma mansoniRESUMEN
Background: Indocyanine Green (ICG) fluorescence imaging has been widely used in the surgical treatment of adult renal cancers, but its application in pediatric renal cancers has rarely been reported. This study aims to summarize the experience of ICG fluorescence imaging in pediatric renal cancers and explores its safety and feasibility. Methods: The clinical features, surgical information, ICG administration regimen, near infrared radiography data in vivo and ex vivo and pathological results of children with renal cancers using ICG navigation were analyzed and summarized. Results: There were 7 cases of renal cancer, including 4 cases of Wilms tumor (WT), 1 case of malignant rhabdoid tumor of the kidney (MRTK) and 2 cases of renal cell carcinoma (RCC). By intraoperative intravenous injection of ICG from 2.5 to 5â mg (0.05-0.67â mg/kg), the tumors were visualized in 6 cases in vivo or ex vivo, and the tumor visualization failed in 1 case due to renal artery embolization before operation. By injecting 5â mg ICG into the normal renal tissue during the operation, 3 patients achieved fluorescent localization of sentinel lymph nodes. No ICG-related adverse reactions were found in any of the patients during or after operation. Conclusions: ICG fluorescence imaging is safe and feasible for renal cancers in children. Intraoperative administration can achieve tumor and sentinel lymph node visualization which will facilitate the development of nephron sparing surgery (NSS). However, the technique is affected by ICG dose, anatomical conditions around the tumor, and renal blood flow. A proper dose of ICG and the complete removal of perirenal fat are helpful for the fluorescence imaging of the tumor. It has potential in the operation of renal cancer in children.