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OBJECTIVE: This study was designed to evaluate TFAP2A-AS1 expression in the dental pulp of teeth with or without pulpitis and to determine the function of TFAP2A-AS1 in pulp cells. METHODS: GSE92681 was analyzed to filter out differentially expressed lncRNAs. Pulp samples from teeth with pulpitis and healthy teeth (control) were examined using real-time (RT) quantitative polymerase chain reaction (qPCR). Human dental pulp stem cells (hDPSCs) were cultured in a specific medium for osteogenic induction, or treated with lipopolysaccharide (LPS) to simulate inflammation. The viability and apoptosis of human DPSCs (hDPSCs) were determined by XTT assay and apoptosis detection kit. Inflammation was induced by LPS and assessed by measuring the expression and release of inflammatory cytokines after TFAP2A-AS1 knockdown. Osteogenic differentiation of hDPSCs was investigated by determining expression levels of osteogenic markers and alkaline phosphatase (ALP) activity after TFAP2A-AS1 overexpression. The downstream microRNA (miRNA) was predicted. Dual-luciferase reporter was used to confirm the binding between miR-32-5p and TFAP2A-AS1. RESULTS: The expression of TFAP2A-AS1 was evaluated in inflamed pulp using RT-qPCR. TFAP2A-AS1 had a discriminatory ability for healthy individuals and patients with pulpitis. The expression of TFAP2A-AS1 decreased upon the osteogenic differentiation of hDPSCs, and increased upon the LPS induction. TFAP2A-AS1 can reverse the osteogenic differentiation of hDPSCs, as evidenced by decreased levels of dentine sialophosphoprotein, dentin matrix protein-1, and ALP activity. TFAP2A-AS1 knockdown can promote cell proliferation of hDPSCs and relieve LPS-induced inflammation, as evidenced by decreased levels of TNF-α, IL-1ß, and IL-6. miR-32-5p was identified as a downstream miRNA of TFAP2A-AS1. CONCLUSION: This study demonstrated the expression and potential function of TFAP2A-AS1 in the human dental pulp. TFAP2A-AS1 can inhibit odontogenic differentiation but promote inflammation in pulp cells.
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Pulpa Dental , MicroARNs , Pulpitis , ARN Largo no Codificante , Factor de Transcripción AP-2 , Humanos , MicroARNs/genética , ARN Largo no Codificante/genética , Pulpa Dental/metabolismo , Pulpa Dental/patología , Pulpitis/metabolismo , Pulpitis/genética , Pulpitis/patología , Factor de Transcripción AP-2/metabolismo , Factor de Transcripción AP-2/genética , Diferenciación Celular/genética , Osteogénesis/genética , Apoptosis/genética , Regulación de la Expresión Génica , Células Cultivadas , Lipopolisacáridos , Células Madre/metabolismoRESUMEN
Exposure to air pollution poses significant risks to human health, including detrimental effects on the reproductive system, affecting both men and women. Our prospective clinical study aimed to assess the impact of prolonged air pollution exposure on sperm quality in male patients attending a fertility clinic. The current study was conducted at Sri Narayani Hospital and Research Centre in Vellore, Tamil Nadu, India, and the study examined sperm samples obtained from individuals with extended exposure to air pollution. Microscopic analysis, including scanning electron microscopy (SEM), was conducted to evaluate sperm morphology. At the same time, atomic absorption spectroscopy (AAS) determined the presence of heavy metals, including Zinc (Zn), Magnesium (Mg), Lead (Pb) and Cadmium (Cd), known to affect sperm production. Our findings revealed that long-term exposure to air pollution adversely affects sperm quality, manifesting in alterations during the spermatogenesis cycle, morphological abnormalities observed through SEM, and impaired sperm motility. Additionally, epidemiological evidence suggests that elevated levels of cadmium and lead in the environment induce oxidative stress, leading to sperm DNA damage and reduced sperm concentrations. These results underscore the urgent need for environmental interventions to mitigate air pollution and protect reproductive health.
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Dysregulation of lncRNAs is a critical factor in the migration and invasion of tumors. Here our study reveals that lncRNA HIF1A-AS2 is highly expressed in breast cancer tissues and various TNBC cell lines. Moreover, we present compelling evidence supporting the role of HIF1A-AS2 in promoting TNBC cell proliferation, metastasis, invasion, and resistance to paclitaxel treatment. Additionally, our transcriptome sequencing analysis identifies MRPS23 as a potential downstream target protein regulated by HIF1A-AS2 and knockdown of HIF1A-AS2 leads to decreased expression of MRPS23 in TNBC cells. Moreover, MRPS23 exhibits similar effects on enhancing cell proliferation, metastasis, invasion, and paclitaxel resistance in TNBC cells. Furthermore, downregulating HIF1A-AS2 suppresses the enhanced functionality observed in TNBC cells due to upregulated MRPS23 expression. These findings suggest that modulation of MRPS23 protein expression by HIF1A-AS2 may influence cellular processes and paclitaxel sensitivity in TNBC cells.
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Cadmium is a common environmental heavy metal that is very toxic and carcinogenic for human and other flora and fauna. Therefore, this study is aimed to evaluate the fisibility of vermicompost fertilizer for cadmium uptake from soil by the root of radish (Raphanus sativus). For the purpose of the study, four different ratios of one case control, 1 per 1, 1 per 4, 2 per 4, 3 per 4 vermicompost fertilizer per soil with 0, 50000 and 100000 µg/L cadmium concentrations was evaluated. Cadmium in the samples was measured using an Atomic Absorption Spectroscopy (AAS). The results showed that the minimum uptake of cadmium by the plant was observed for 3 per 4 ratio of fertilizer per soil. In addition, results revealed that highest growth rate of Raphanus sativus roots occurred in maximum ratio of fertilizer per soil usage (3 per 4). This study showed that vermicompost as a organic fertilizer has a good ability to adsorb cadmium metal from soil. Therfore, vermicompost application can be considered as an inexpensive natural adsorbent in arable land contaminated with cadmium.â¢Heavy metals are very toxic and carcinogenic to human and animals.â¢Adding organic fertilizer to the soil increases the absorption of heavy metal (cadmium) in the soil and prevents it from entering the food chain.â¢The relationship between the concentration of cadmium absorbed by the tuber of radish plant and the percentage of vermicompost added to the soil is presented.
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The Deep South is the epicenter of the HIV-epidemic in the United States, with rural AAs bearing the greatest burden. Traditional efforts to improve testing efforts have been largely unsuccessful due to their failure to recognize and leverage the sociopolitical and cultural factors that affect the uptake of HIV-screening interventions at the community level. The purpose of this study was to gain a deeper understanding of the socio-cultural contexts impacting HIV-testing in the rural South, and to assess strategies to increase testing in rural, Southern communities. Focus groups (n = 8) and semi-structured interviews (n = 31) were conducted among community and faith-based leaders in Alabama and Mississippi, to inform our understanding of local perceptions of HIV infection, barriers and facilitators impacting HIV-testing, and best strategies for improving testing efforts at the local level. Interviews and focus groups were audio-recorded, transcribed verbatim, and analyzed to extract major themes. While both faith-based and community leaders reported at least some stigmatizing attitudes towards HIV infection, faith-based leaders were more likely to report discomfort being around someone with HIV and were more likely to link the spread of HIV to immoral behaviors. The combination of the cultural importance of the Church, deep-seated religiosity among community members, and faith-based messages associating HIV infection with immorality directly impacted HIV stigma within the community-in turn, decreasing willingness to participate in HIV-testing, disclose positive HIV serostatus, or openly discuss transmission protection behaviors. The Church was identified as crucial to include to improve HIV-testing efforts in the rural South, due to their prominent sociopolitical roles within communities and ability to influence community members' perceptions of HIV stigma. Faith-based leaderships should be included in initiatives to increase improve HIV-testing and awareness of status and reduce HIV disparities in the Deep South.
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BACKGROUND: Disulfidptosis is an emerging form of cellular death resulting from the binding of intracellular disulfide bonds to actin cytoskeleton proteins. This study aimed to investigate the expression and prognostic significance of hub disulfidptosis-related lncRNAs (DRLRs) in R0 resected hepatocellular carcinoma (HCC) as well as their impact on the malignant behaviour of HCC cells. METHODS: A robust signature for R0 resected HCC was constructed using least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression and was validated in an independent internal validation cohort to predict the prognosis of R0 HCC patients. Comprehensive bioinformatics analysis was performed on the hub DRLRs (KDM4A-AS1, MKLN1-AS, and TMCC1-AS1), followed by experimental validation using quantitative real-time polymerase chain reaction (qRTâPCR) and cellular functional assays. RESULTS: The signature served as an independent prognostic factor applicable to R0 HCC patients across different age groups, tumour stages, and pathological characteristics. Gene Ontology (GO) and gene set enrichment analysis (GSEA) revealed hub pathways associated with this signature. The high-risk group presented an increased abundance of M0 macrophages and activated memory CD4 T cells as well as elevated macrophage and major histocompatibility complex (MHC) class I expression. High-risk R0 HCC patients also presented increased tumour immune dysfunction and exclusion scores (TIDEs), mutation frequencies, and tumour mutational burdens (TMBs). Drug sensitivity analysis revealed that high-risk patients were more responsive to drugs, including GDC0810 and osimertinib. High expression levels of the three hub DRLRs were detected in R0 HCC tissues and HCC cell lines. Functional assays revealed that the three hub DRLRs enhanced HCC cell proliferation, migration, and invasion. CONCLUSIONS: A signature was constructed on the basis of three DRLRs, providing novel insights for personalized precision therapy in R0 HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , ARN Largo no Codificante/genética , Pronóstico , Masculino , Biomarcadores de Tumor/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Proliferación Celular/genética , Línea Celular Tumoral , Biología Computacional/métodosRESUMEN
Harbors on all coasts regularly silt up, receiving sedimentary inputs that progressively reduce the water depths available for navigation. Consequently, they are routinely dredged to guarantee the depths necessary for navigation. Sediments act as a reservoir for anthropogenic contaminants such as heavy metals and persistent organic pollutants (POPs) that enter the aquatic system associated with particles or in solution. The objective of this study is to assess the state of pollution by POPs and heavy metals such as copper and zinc, used in large quantities in antifouling paints, in the sediments of the port of Oran. These were characterized by different methods: size, XRD, calcination, FTIR, NMR, GC-MS, and AAS, in order to determine their main characteristics and heavy metals and POPs content. The particle size is determined by laser particle size distribution. Thus, sediments from Oran port are composed of means and end sands, silt, and clay. The XRD analysis shows that the sediments consist mainly of silicates and calcite. The organic matter was determined by ignition loss at 450 and 550 °C; it is about 7%. Analysis by FTIR, 1H and 13C NMR, and GC-MS of POPs excerpts shows that the sediments are highly polluted by aliphatic and aromatic hydrocarbons (3372 mg/kg). Finally, metals were determined by AAS method. The results show significant pollution of Zn (313.5 mg/kg) and moderate pollution by Cu (75.6 mg/kg).
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Monitoreo del Ambiente , Sedimentos Geológicos , Metales Pesados , Contaminantes Químicos del Agua , Sedimentos Geológicos/química , Metales Pesados/análisis , Contaminantes Químicos del Agua/análisis , Argelia , Contaminantes Orgánicos PersistentesRESUMEN
The Chinese yam (Dioscorea polystachya, DP) is promising for the food and pharmaceutical industries due to its nutritional value and pharmaceutical potential. Its proper cultivation is therefore of interest. An insufficient supply of minerals necessary for plant growth can be manifested by discoloration of the leaves. In our earlier study, magnesium deficiency was excluded as a cause. As a follow-up, this work focused on manganese and molybdenum. To quantify both minerals in leaf extracts of DP, analytical methods based on atomic absorption spectrometry (AAS) using the graphite furnace sub-technique were devised. The development revealed that the quantification of manganese works best without using any of the investigated modifiers. The optimized pyrolysis and atomization temperatures were 1300 °C and 1800 °C, respectively. For the analysis of molybdenum, calcium proved to be advantageous as a modifier. The optimum temperatures were 1900 °C and 2800 °C, respectively. Both methods showed satisfactory linearity for analysis. Thus, they were applied to quantify extracts from normal and discolored leaves of DP concerning the two minerals. It was found that discolored leaves had higher manganese levels and a lower molybdenum content. With these results, a potential explanation for the discoloration could be found.
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Dioscorea , Manganeso , Molibdeno , Hojas de la Planta , Espectrofotometría Atómica , Molibdeno/análisis , Molibdeno/química , Manganeso/análisis , Hojas de la Planta/química , Espectrofotometría Atómica/métodos , Dioscorea/química , Extractos Vegetales/química , Extractos Vegetales/análisisRESUMEN
RNAs transcribing more than 200 nucleotides without encoding proteins are termed long non-coding RNAs (LncRNAs). LncRNAs can be used as decoy molecules, signal molecules, scaffolds, and guide molecules. Long non-coding RNAs can interact with DNA, chromatin-modifying complexes, and transcriptional regulatory proteins, regulating gene expression in the cell nucleus. It is distributed in cytoplasm; they also participate in mRNA degradation and translational regulation via miRNAs, other transcription products, and proteins. They play a significant role in the development of various diseases, including tumors. Cancer seriously threatens human life and health. Regretfully, a great deal of newly diagnosed cancer patients found to have metastasized. RNF144A-AS1, also referred to as GRASLND, was initially recognized for its regulation of chondrogenic differentiation in MSCs. Focusing on RNF144A-AS1, this review summarizes and discusses the latest progress of RNF144A-AS1 in bladder cancer, glioblastoma, papillary renal cell carcinoma, gastric cancer, osteosarcoma, head and neck squamous cell carcinoma, and ovarian cancer. RNF144A-AS1 has good potential in tumor treatment and diagnosis.
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Andrógenos , Neoplasias Meníngeas , Meningioma , Humanos , Andrógenos/efectos adversos , Estudios de Cohortes , Masculino , Factores de RiesgoRESUMEN
BACKGROUND: Long noncoding RNAs (lncRNAs) play vital regulatory functions in non-small cell lung cancer (NSCLC). Cisplatin (DDP) resistance has significantly decreased the effectiveness of DDP-based chemotherapy in NSCLC patients. This study aimed to investigate the effects of SH3PXD2A antisense RNA 1 (SH3PXD2A-AS1) on DDP resistance in NSCLC. METHODS: Proliferation and apoptosis of DDP-resistant NSCLC cells were detected using cell counting kit-8 and flow cytometry assays. The interaction between SH3PXD2A-AS1 and sirtuin 7 (SIRT7) was assessed using co-immunoprecipitation (Co-IP), RNA pull-down, RNA immunoprecipitation (RIP), RNA fluorescence in situ hybridization, and immunofluorescence assays, while succinylation (SUCC) of Forkhead Box M1 (FOXM1) was analyzed by IP and Western blot assays. The role of SH3PXD2A-AS1 in vivo was explored using a xenografted tumor model. RESULTS: Expression of SH3PXD2A-AS1 was found elevated in DDP-resistant NSCLC cells, while it's knocking down translated into suppression of cell viability and promotion of apoptosis. Moreover, silencing of SH3PXD2A-AS1 resulted in decreased FOXM1 protein level and enhanced FOXM1-SUCC protein level. The SIRT7 was found to interact with FOXM1, translating into inhibition of FOXM1 SUCC at the K259 site in human embryonic kidney (HEK)-293T cells. Overexpressing of SIRT7 reversed the increase of FOXM1-SUCC protein level and apoptosis, and the decrease of cell viability induced by silencing of SH3PXD2A-AS1. In tumor-bearing mice, SH3PXD2A-AS1 inhibition suppressed tumor growth and the protein levels of Ki67, SIRT7, and FOXM1. CONCLUSION: SH3PXD2A-AS1 promoted DDP resistance in NSCLC cells by regulating FOXM1 SUCC via SIRT7, offering a promising therapeutic approach for NSCLC.
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Apoptosis , Carcinoma de Pulmón de Células no Pequeñas , Cisplatino , Resistencia a Antineoplásicos , Proteína Forkhead Box M1 , Neoplasias Pulmonares , ARN Largo no Codificante , Sirtuinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Cisplatino/farmacología , Cisplatino/uso terapéutico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Animales , Ratones , Sirtuinas/metabolismo , Sirtuinas/genética , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Desnudos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Background: HIF1A-AS1, an antisense transcript of HIF1α gene, is a 652-bp LncRNA that is globally expressed in multiple tissues of animals. Recent evidence indicated that HIF1A-AS1 was involved in tumorigenesis of several types of cancer. However, the role of lncRNA in PC has not been reported, and the molecular mechanism remains elusive. Results: In order to investigate the role of HIF1A-AS1 in PC, it was overexpressed in some PC cell lines (PANC-1, PATU8988 and SW1990), and a series of experiments including cell viability detection, flow cytometry, transwell migration, clone formation and wound healing were performed. Functionally, the results indicated that overexpression of HIF1A-AS1 could greatly inhibit proliferation and migration and promote apoptosis of PC cells. Moreover, the isobaric tags for relative and absolute quantification (iTRAQ) quantitative proteomics analysis was implemented to explore the underlying mechanism and the results indicated that OE of HIF1A-AS1 globally affected the expression levels of multiple proteins associated with metabolism of cancer. At last, the network analysis revealed that most of these differentially expressed proteins (DEPs) were integrated and severed essential roles in regulatory function. In view of this, we guessed HIF1A-AS1 overexpression induced the dysfunction of metabolism and disordered proteins' translation, which may account for its excellent tumour suppressor effect. Conclusions: HIF1A-AS1 altered the cell function of PC cell lines via affecting the expression of numerous proteins. In summary, HIF1A-AS1 may exhibit a potential therapeutic effect on PC, and our study provided useful information in this filed.
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Estra-4,9-diene-3,17-dione (dienedione) is an anabolic-androgenic steroid (AAS) available on the market as a dietary supplement for bodybuilding. It is prohibited in both human and equine sports due to its potential performance-enhancing effect. With the rare presence of the 4,9-diene configuration in endogenous steroids, dienedione has been considered as a synthetic AAS. Nevertheless, the reoccurring detection of dienedione in entire male horse urine samples led to the investigation of its possible endogenous nature in horses, and its endogenous nature in entire male horses has been recently confirmed and reported by the authors' laboratory. While dienedione is not detected in castrated horses (geldings), it is essential to study its elimination and identify its metabolites for its effective control. To study the elimination and biotransformation of dienedione, administration experiments were performed by giving three castrated horses (geldings) each single oral dose of 1500 mg of dienedione powder for seven consecutive days. The postulated in vivo metabolites included 17-hydroxyestra-4,9-dien-3-one (M1a and M1b), hydroxylated dienedione (M2a, M2b, M3a, M3b, M4, M5) and hydroxylated M1 (M6a, M6b, M7a, M7b, M8a and M8b), formed from hydroxylation and reduction of dienedione. To control the misuse of dienedione in geldings, M3a and M3b are the potential targets that gave the longest detection time, which could be detected for up to 2-5 days in urine and 0.4-4 days in plasma.
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Current trends are promoting youth, beauty, health, and fitness. Individuals often seek out remedies, such as medicines or dietary supplements (DS), to achieve these goals. However, highly processed foods, chronic stress, and environmental pollution contribute to the development of civilization diseases. The aim of this study was to evaluate the mercury (Hg) content in medicines and DS that are available in Poland. A total of 139 preparations were tested (75 drugs, 64 DS). The medicines contained preparations belonging to antibacterial, antiviral, antifungal; analgesic, antipyretic, and anti-inflammatory; heart and blood vessel disease preventatives; respiratory tract infections treatment; diuretics; aiding digestion; supplements; antidiarrhoeals; anti-allergics; anti-rheumatics; antibiotics; and others. The tested dietary supplements had an effect on the following: improve the condition of skin, hair, and nails; vitamins; minerals; probiotics; weight loss; special for women; and others. The Hg content of the samples was determined using atomic absorption spectrometry (AAS). The Hg content of all the preparations varied widely (0.1-57.4 µg/kg), with a median Hg concentration of 1.2 µg/kg. The median Hg concentration for medicines was 0.8 µg/kg, prescription medicines having higher Hg concentrations (0.9 µg/kg) than over-the-counter (OTC) drugs (0.5 µg/kg). For DS, the Hg content was found to be higher than for drugs, at 2.0 µg/kg. The herbal preparations showed the highest Hg content among the individual DS groups (3.4 µg/kg). The Hg concentrations in the tested drug and DS samples did not exceed acceptable standards. However, if multiple pharmaceutical preparations are taken simultaneously over a long period of time, and there is existing environmental exposure, there is a possibility of Hg concentration accumulation and adverse health effects.
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LncRNAs have been demonstrated to regulate biological processes in malignant tumors. In our previous study, we identified the immune-related LncRNA RNF144A-AS1 as a potential regulator in SKCM. However, its precise function and regulatory mechanism remain unclear. In this study, we observed upregulation of RNF144A-AS1 in SKCM and found that knockdown of RNF144A-AS1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition abilities of melanoma cells. Mechanistically, as a high-risk prognostic factor, RNF144A-AS1 regulated biological processes of SKCM by interacting with TAF15 through an RNA-binding protein-dependent (RBP-dependent) manner. Furthermore, we confirmed that TAF15 activated downstream transcriptional regulation of YAP1 to modulate malignant behaviors in melanoma cells. In vivo experiments revealed that knockdown of RNF144A-AS1 inhibited tumorigenic capacity of melanoma cells and exhibited promising therapeutic effects. Collectively, these findings highlight the significance of the RNF144A-AS1/TAF15/YAP1 axis in promoting malignant behaviors in SKCM and provide novel insights into potential prognostic biomarkers and therapeutic targets for this disease.
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Neuroblastoma (NB), a common solid tumour in young children originating from the sympathetic nervous system during embryonic development, poses challenges despite therapeutic advances like high-dose chemotherapy and immunotherapy. Some survivors still grapple with severe side effects and drug resistance. The role of lncRNA NUTM2A-AS1 has been explored in various cancers, but its function in drug-resistant NB progression is unclear. Our study found that NUTM2A-AS1 expression in cisplatin-resistant NB cells increased in a time- and dose-dependent manner. Knockdown of NUTM2A-AS1 significantly improved NB cell sensitivity to cisplatin and inhibited metastatic abilities. Additionally, we identified B7-H3, an immune checkpoint-related protein, as a NUTM2A-AS1-associated protein in NB cells. NUTM2A-AS1 was shown to inhibit the protein degradation of B7-H3. Moreover, NUTM2A-AS1 modulated immune evasion in cisplatin-resistant NB cells through B7-H3. Furthermore, NUTM2A-AS1 expression in cisplatin-resistant NB cells was transactivated by NR1D1. In summary, our results unveil the molecular or biological relationship within the NR1D1/NUTM2A-AS1/B7-H3 axis in NB cells under cisplatin treatment, providing an intriguing avenue for fundamental research into cisplatin-resistant NB.
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Antígenos B7 , Cisplatino , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Neuroblastoma , ARN Largo no Codificante , Humanos , Neuroblastoma/genética , Neuroblastoma/patología , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/metabolismo , Resistencia a Antineoplásicos/genética , Antígenos B7/metabolismo , Antígenos B7/genética , ARN Largo no Codificante/genética , Cisplatino/farmacología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Evasión Inmune , Animales , Proteolisis/efectos de los fármacos , RatonesRESUMEN
The evolving prevalence of anabolic androgenic steroids (AAS) abuse among nonathletes is alarming because of the known harm to an individual's health. Among the adverse effects of AAS abuse, male infertility and sexual dysfunction have been often reported in the literature, but little is known regarding its actual prevalence, possible underpinning mechanisms, and potential treatments either during or post-AAS usage. Thus, the current narrative review summarizes the state-of-art regarding the effects of AAS on male fertility and sexual function. Evidence was gathered from the latest reviews and recent original studies, specifically from prospective cohorts and clinical trials, ultimately resulting in five main topics of discussion. First, AAS usage is briefly characterized by its historical background, main physiological mechanisms, and the most frequently used AAS substances. Second, data on the prevalence of AAS-induced male infertility and sexual dysfunction are described. Third, some new insights on possible underpinning mechanisms of AAS-induced male infertility and sexual dysfunction are thoroughly discussed, with particular attention to histological data derived from animal models and the latest insights from prospective cohorts in humans. Fourth, the potential treatments during and after the AAS usage are presented, highlighting the odds of resolving male infertility and sexual dysfunction. Fifth, future directions on this topic are discussed, focusing on the methodological robustness of scientific studies.
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The lncRNA NUTM2A-AS1 has been shown to be dysregulated in gastric cancer, while the roles in glioma is unclear. The aim of this study was to investigate the roles and potential mechanisms of lncRNA NUTM2A-AS1 in the proliferation and apoptosis of glioma cells. The StarBase software and dual luciferase reporter assay were used to identify the relationship between lncRNA NUTM2A-AS1 and miR-376a-3p, and miR-376a-3p and YAP1. The expression of lncRNA NUTM2A-AS1, miR-376a-3p, and YAP1 in human glioma cell lines was detected by qRT-PCR. MTT and flow cytometry were used to detect the effects of lncRNA NUTM2A-AS1 or miR-376a-3p on the proliferation and apoptosis of U251 and A172 cells, respectively. In addition, changes of Bax and Bcl-2 expression in glioma cells were further verified by western blotting and qRT-PCR. The results showed that the expression of lncRNA NUTM2A-AS1 was elevated in glioma cell lines, while miR-376a-3p was decreased. LncRNA NUTM2A-AS1 was negatively correlated with miR-376a-3p. Silencing of lncRNA NUTM2A-AS1 enhanced the levels of miR-376a-3p, leading to reduced cell proliferation and increased apoptosis in glioma cells. YAP1 was a direct target of miR-376a-3p, and it was negatively regulated by miR-376a-3p in U251 and A172 cells. Further mechanistic studies suggested that miR-376a-3p reduced glioma cell proliferation and increased apoptosis by inhibiting YAP1 expression. In addition, lncRNA NUTM2A-AS1 positively regulated of YAP1 expression in glioma cells. In conclusion, silencing of lncRNA NUTM2A-AS1 inhibited proliferation and induced apoptosis in human glioma cells via the miR-376a-3p/YAP1 axis.
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Recently, evidence of aromatic amine antioxidants (AAs) existence in the dust of the electronic waste (e-waste) dismantling area has been exposed. However, there are limited studies investigating occupational exposure and toxicity associated with AAs and their transformation products (p-phenylenediamines-quinones, i.e., PPD-Qs). In this study, 115 dust and 42 hand wipe samples collected from an e-waste recycling industrial park in central China were analyzed for 19 AAs and 6 PPD-Qs. Notably, the median concentration of ∑6PPD-Qs (1,110 ng/g and 1,970 ng/m2) was significantly higher (p < 0.05, Mann-Whitney U test) than that of ∑6PPDs (147 ng/g and 34.0 ng/m2) in dust and hand wipes. Among the detected analytes, 4-phenylaminodiphenylamine quinone (DPPD-Q) (median: 781 ng/g) and 1,4-Bis(2-naphthylamino) benzene quinone (DNPD-Q) (median: 156 ng/g), were particularly prominent, which were first detected in the e-waste dismantling area. Occupational exposure assessments and nuclear receptor interference ability, conducted through estimated daily intake (EDI) and molecular docking analysis, respectively, indicated significant occupational exposure to PPD-Qs and suggested prioritized Liver X receptors (LXRs) disruption potential of PPDs and PPD-Qs. The study provides the first evidence of considerable levels of AAs and PPD-Qs in the e-waste-related hand wipe samples and underscores the importance of assessing occupational exposure and associated toxicity effects.
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Antioxidantes , Polvo , Residuos Electrónicos , Exposición Profesional , Reciclaje , Exposición Profesional/análisis , Humanos , Polvo/análisis , China , Quinonas/análisis , Aminas/análisisRESUMEN
BACKGROUND: In recent years, significant attention has been directed towards long non-coding RNA NUT family member 2A antisense RNA 1 (NUTM2A-AS1) for its oncogenic role in tumours. This study aimed to investigate the functional and molecular mechanisms underlying NUTM2A-AS1 in prostate cancer (PCa). METHODS: NUTM2A-AS1, miR-376a-3p, and protein arginine methyltransferase 5 (PRMT5) levels were assessed in PCa samples and matched non-cancerous prostate samples. The DU145 cell line was conditioned to undergo transfection with relevant plasmids, and a cell counting kit-8 assay was performed to evaluate cell proliferation. A Transwell assay was conducted to analyse cell migration or invasion. Cell apoptosis was assessed using an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and flow cytometry. A tumour sphere formation assay was conducted to assess the ability of PCa cells to form tumour spheres. RESULTS: We found elevated expression of NUTM2A-AS1 and PRMT5 and decreased expression of miR-376a-3p in PCa samples. Inhibition of NUTM2A-AS1 or overexpression of miR-376a-3p led to reduced cell proliferation and diminished cancer stem cell-like traits in vitro. NUTM2A-AS1 regulated miR-376a-3p through competitive absorption, thereby modulating PRMT5. Up-regulation of PRMT5 nullified the therapeutic effects of inhibiting NUTM2A-AS1 or overexpressing miR-376a-3p in DU145 cells. CONCLUSIONS: NUTM2A-AS1 promotes cancer stem cell-like traits in PCa cells by targeting PRMT5 through miR-376a-3p. Therefore, these NUTM2A-AS1-based novel insights into tumour therapy hold promise for patients with PCa.