RESUMO
The molecular mechanisms driving the development of cervical adenocarcinoma (CADC) and optimal patient management strategies remain elusive. In this study, we have identified circMAN1A2_009 as an oncogenic circular RNA (circRNA) in CADC. Clinically, circMAN1A2_009 showed significant upregulation in CADC tissues, with an impressive area under the curve value of 0.8075 for detecting CADC. Functional studies, involving both gain-of-function and loss-of-function experiments, revealed that circMAN1A2_009 suppressed reactive oxygen species accumulation and apoptosis, and boosted cell viability in CADC cells. Conversely, silencing circMAN1A2_009 reversed these effects. Further mechanistic investigations indicated that circMAN1A2_009 interacted with YBX1, facilitating the phosphorylation levels of YBX1 at serine 102 (p-YBX1S102) and facilitating YBX1 nuclear localization through sequence 245-251. This interaction subsequently increased the activity of the glyoxalase 1 (GLO1) promoter, leading to the activation of GLO1 expression. Consistently, inhibition of either YBX1 or GLO1 mirrored the biological effects of circMAN1A2_009 in CADC cells. Additionally, knockdown of YBX1 or GLO1 partially reversed the oncogenic behaviors induced by circMAN1A2_009. In conclusion, our findings propose circMAN1A2_009 as a potential oncogene and a promising indicator for diagnosing and guiding therapy in CADC patients.
RESUMO
In this study, a microcosm experiment was conducted to investigate the effects of Na2S2O8 preoxidation combined with biostimulation on petroleum-contaminated soil remediation. The response of microbial community during this process was explored using BIOLOG ECO microplate carbon utilization method and 16â¯s rDNA high-throughput sequencing. The results showed that use of 10â¯mg/g Na2S2O8 removed 19.8â¯% of the petroleum hydrocarbons, reduced soil biotoxicity and did not affect soil microbial activity compared to other concentrations. Therefore, sodium persulfate of ca. 10â¯mg/g was used to oxidize petroleum in soil before the biostimulation experiment with organic and inorganic fertilizers. Our finding showed that the content of total petroleum hydrocarbons (TPHs) in soil was reduced by 43.3â¯% in inorganic fertilizer treatment after 60 days. The results of BIOLOG ECO microplate carbon utilization analysis and 16â¯S rDNA high-throughput sequencing further confirmed that biostimulation quickly restored the microbial activities in oxidant treated soil. The main marker bacteria in chemical oxidation combined with biostimulation remediation were Arthrobacter and Paenarthrobacter, and their relative abundances were both significantly negatively correlated with the content of petroleum hydrocarbons in soil.
Assuntos
Biodegradação Ambiental , Oxirredução , Petróleo , Microbiologia do Solo , Poluentes do Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Fertilizantes/análise , Sulfatos , Hidrocarbonetos , Compostos de Sódio/toxicidade , Solo/química , Arthrobacter , Recuperação e Remediação Ambiental/métodos , Bactérias/efeitos dos fármacos , Bactérias/genéticaRESUMO
Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which is related to tumorigenesis and progression. We explored the possible mechanisms by which OSA may promote the development of non-small cell lung cancer (NSCLC). In this study, NSCLC cells with and without miR-106a-5p inhibition were exposed to IH or room air (RA), and subsequently, exosomes were extracted and identified. Macrophages were incubated with these exosomes to detect the expression of the STAT3 signaling pathway and M2-type macrophage markers, as well as the effect of the macrophages on the malignancy of NSCLC cells. A nude mouse tumorigenesis model was constructed to detect the effects of exosomal miR-106a-5p on M2 macrophage polarization and NSCLC cell malignancy. Our results showed that IH exosomes promoted the polarization of M2 macrophages, thereby promoting the proliferation, invasion, and metastasis of NSCLC cells. Further, Based on microarray analysis of RA and IH exosomes, we discovered that miR-106a-5p, transferred to the macrophages through exosomes, participated in this mechanism by promoting M2 macrophage polarization via down-regulating PTEN and activating the STAT3 signaling pathway in vitro and in vivo. For patients with NSCLC and OSA, exosomal miR-106a-5p levels showed a positive relation to AHI. Exosomal miR-106a-5p represents a potential therapeutic target among patients with concomitant cancer and NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Exossomos , Neoplasias Pulmonares , Camundongos Nus , MicroRNAs , Fator de Transcrição STAT3 , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Humanos , Animais , Exossomos/metabolismo , Exossomos/genética , Camundongos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Masculino , Macrófagos/metabolismo , Linhagem Celular Tumoral , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Proliferação de Células , Apneia Obstrutiva do Sono/genética , Apneia Obstrutiva do Sono/metabolismo , Transdução de Sinais , Hipóxia/metabolismo , Hipóxia/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Cadmium (Cd) pollution has been rapidly increasing due to the global rise in industries. Cd not only harms the ecological environment but also endangers human health through the food chain and drinking water. Therefore, the remediation of Cd-polluted soil is an imminent issue. In this work, ryegrass and a strain of Cd-tolerant bacterium were used to investigate the impact of inoculated bacteria on the physiology and biochemistry of ryegrass and the Cd enrichment of ryegrass in soil contaminated with different concentrations of Cd (4 and 20 mg/kg). The results showed that chlorophyll content increased by 24.7% and 41.0%, while peroxidase activity decreased by 56.7% and 3.9%. In addition, ascorbic acid content increased by 16.7% and 6.3%, whereas glutathione content decreased by 54.2% and 6.9%. The total Cd concentration in ryegrass increased by 21.5% and 10.3%, and the soil's residual Cd decreased by 86.0% and 44.1%. Thus, the inoculation of Cd-tolerant bacteria can improve the antioxidant stress ability of ryegrass in Cd-contaminated soil and change the soil's Cd form. As a result, the Cd enrichment in under-ground and above-ground parts of ryegrass, as well as the biomass of ryegrass, is increased, and the ability of ryegrass to remediate Cd-contaminated soil is significantly improved.
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The antioxidant properties of crocin are attracting interest, yet the underlying mechanisms by which crocin mitigates oxidative stress-induced intestinal damage have not been determined. This study aimed to elucidate the effects of crocin on oxidative stress, apoptosis, and intestinal epithelial injury in intestinal epithelial cells (IPEC-J2). Using an H2O2-induced oxidative stress model in IPEC-J2 cells, crocin was added to assess its effects. Cell viability and apoptosis were evaluated using methyl thiazolyl tetrazolium assays and flow cytometry. Additionally, oxidative stress markers, such as superoxide dismutase (SOD), catalase (CAT), reactive oxygen species (ROS), and malondialdehyde (MDA), were quantified. We investigated, in which cell oxidation and apoptosis were measured at the gene and protein levels and employed transcriptome analysis to probe the mechanism of action and validate relevant pathways. The results showed that crocin ameliorates H2O2-induced oxidative stress by reducing ROS and MDA levels and by countering the reductions in CAT, total antioxidant capacity, and SOD. Crocin also attenuates the upregulation of key targets in the Nrf2 pathway. Furthermore, it effectively mitigated IPEC-J2 cell apoptosis caused by oxidative stress, as evidenced by changes in cell cycle factor expression, apoptosis rate, mitochondrial membrane potential, and apoptosis pathway activity. In addition, crocin preserves the integrity of the intestinal barrier by protecting tight junction proteins against oxidative stress. Transcriptome sequencing analysis suggested that the mitochondrial pathway may be a crucial mechanism through which crocin exerts its protective effects. In summary, crocin decreases oxidative stress molecule formation, inhibits Nrf2 pathway activity, prevents apoptosis-induced damage, enhances oxidative stress resistance in IPEC-J2 cells, and maintains redox balance in the pig intestine.
Assuntos
Antioxidantes , Apoptose , Carotenoides , Peróxido de Hidrogênio , Estresse Oxidativo , Espécies Reativas de Oxigênio , Carotenoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Animais , Linhagem Celular , Peróxido de Hidrogênio/toxicidade , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Suínos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacosRESUMO
The perennial ryegrass Lolium perenne can be used in conjunction with cadmium (Cd)-tolerant bacteria such as Cdq4-2 (Enterococcus spp.) for bioremediation of Cd-contaminated soil. In this study, a theoretical basis was provided to increase the efficiency of L. perenne remediation of Cd-contaminated soil using microorganisms to maintain the stability of the soil microbiome. The experimental design involved three treatment groups: CK (soil without Cd addition) as the control, 20 mg·kg-1 Cd-contaminated soil, and 20 mg·kg-1 Cd-contaminated soil + Cdq4-2, all planted with L. perenne. The soil was collected on day 60 to determine the soil microbial activity and bacterial community structure and to analyze the correlation between soil variables, the bacterial community, available Cd content in the soil, Cd accumulation, and L. perenne growth. The soil microbial activity and bacterial community diversity decreased under Cd stress, and the soil microbial community composition was changed; while inoculation with Cdq4-2 significantly increased soil basal respiration and the activities of urease, invertase, and fluorescein diacetate (FDA) hydrolase by 83.65%, 79.72%, 19.88%, and 96.15% respectively; and the stability of the community structure was also enhanced. The Actinobacteriota biomass, the amount of available Cd, and the above- and belowground Cd content of L. perenne were significantly negatively correlated with the total phosphorus, total potassium, and pH. The activity of urease, invertase, and FDA hydrolase were significantly positively correlated with the biomasses of Acidobacteriota and L. perenne and significantly negatively correlated with the Chloroflexi biomass. Further, the available soil Cd content and the above- and belowground Cd levels of L. perenne were significantly positively correlated with the Actinobacteriota biomass and significantly negatively correlated with the Gemmatimonadetes biomass. Overall, inoculating Cd-tolerant bacteria improved the microbial activity, diversity, and abundance, and changed the microbial community composition, facilitating the remediation of Cd-contaminated soil by L. perenne.