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BACKGROUND: Epigenetic alterations contribute greatly to the development and progression of colorectal cancer, and effect of aberrant miR-622 expression is still controversial. This study aimed to discover miR-622 regulation in CRC proliferation. METHODS: miR-622 expression and prognosis were analyzed in clinical CRC samples from Nanfang Hospital. miR-622 regulation on cell cycle and tumor proliferation was discovered, and FOLR2 was screened as functional target of miR-622 using bioinformatics analysis, which was validated via dual luciferase assay and gain-of-function and loss-of-function experiments both in vitro and in vivo. RESULTS: miR-622 overexpression in CRC indicated unfavorable prognosis and it regulated cell cycle to promote tumor growth both in vitro and in vivo. FOLR2 is a specific, functional target of miR-622, which negatively correlates with signature genes in cell cycle process to promote CRC proliferation. CONCLUSIONS: miR-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation, proposing a novel mechanism and treatment target in CRC epigenetic regulation of miR-622.
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Proliferação de Células , Neoplasias Colorretais , Receptor 2 de Folato , MicroRNAs , Humanos , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Epigênese Genética , Receptor 2 de Folato/genética , Receptor 2 de Folato/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismoRESUMO
In recent years, a substantial number of studies have been dedicated to exploring the potential benefits of probiotics in aquaculture. Rhodobacter sphaeroides can be used in aquaculture-related environmental bioremediation, and its protein is also used as a feed additive in Penaeus vannamei culture. To investigate the effects of releasing R. sphaeroides as environmental probiotics on P. vannamei, we employed 16S rRNA gene and mRNA transcriptome sequencing. Our study focused on assessing alterations in intestinal bacteria and intestinal gene expression in P. vannamei, establishing correlations between them. Our findings revealed a significant increase in the relative abundances of Rhodobacter, Paracoccus, Sulfitobacter, and other bacterial OTUs within the intestinal bacterial community. Additionally, we observed enhanced complexity and stability in the intestinal bacterial correlation network, indicating improved synergy among bacteria and reduced competition. Moreover, the introduction of R. sphaeroides resulted in the down-regulation of certain immune genes and the up-regulation of genes linked to growth and metabolism in the intestinal tissues of P. vannamei. Importantly, we identified a noteworthy correlation between the changes in intestinal bacteria and these alterations in intestinal tissue gene expressions. By conducting analyses of the intestinal bacterial community and intestinal tissue transcriptome, this study revealed the effects of releasing R. sphaeroides as sediment probiotics in P. vannamei culture water. These results serve as vital scientific references for the application of R. sphaeroides in P. vannamei aquaculture.
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Penaeidae , Probióticos , Rhodobacter sphaeroides , Animais , Transcriptoma , Rhodobacter sphaeroides/genética , RNA Ribossômico 16S , AquiculturaRESUMO
The impact of carbonate alkalinity in saline-alkaline water on aquatic organisms, particularly Penaeus vannamei, a significant species in aquaculture, remains a critical area of study. To elucidate the acute response mechanisms of P. vannamei to elevated carbonate alkalinity environments, we utilized 16S rRNA gene and transcriptome sequencing technologies to analyze intestinal bacteria and gene expressions within various tissues. Our investigation revealed notable changes in specific intestinal bacterial OTUs, whose abundances varied preceding the overall bacterial community, indicating the sensitivity to carbonate alkalinity exposure. These shifts are accompanied by a simplification in bacterial networks and alterations in pathogenic OTUs, notably Aeromonas OTU. Concurrently, gene expression variations were observed across the hepatopancreas, gills, muscles, and intestines, with decreasing numbers of DEGs in the mentioned order. Annotation of these DEGs revealed enrichments in pathways related to transport, catabolism, immune responses, circulatory functions, and lipid metabolism. Notably, correlations between specific intestinal bacterial OTUs and gene expression shifts were identified across these tissues. Several OTUs, attributed to Rhizobiales, Saccharimonadales, Acidovora, and Aeromona, exhibited a correlation with DEGs in all four tissues, primarily associated with amino acid metabolism, signal transduction, and transport and catabolism pathways. Our study provides comprehensive insights into the dynamic responses of P. vannamei to elevated carbonate alkalinity stress. These findings contribute crucial knowledge for effective P. vannamei cultivation in saline-alkaline water, advancing our understanding in this field.
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Penaeidae , Animais , RNA Ribossômico 16S , Perfilação da Expressão Gênica/veterinária , Carbonatos , Bactérias , Água , TranscriptomaRESUMO
The dairy industry generates substantial wastewater, which is commonly treated using integrated anaerobic hydrolysis and aerated biofilm reactors. However, the bacterial composition and functional differences within the generated floccules remain unclear. In this study, we employed 16S rRNA and metagenomic sequencing to compare bacterial communities and enzyme gene profiles between suspended floccules from the hydrolysis ponds and the aeration ponds. Results revealed that the bacterial phyla Firmicutes, Proteobacteria, and Bacteroidetes dominated the wastewater treatment system and the relative abundance of these bacterial phyla varied in each pond. Additionally, the aeration ponds exhibited higher bacterial operational taxonomic units and enzyme gene abundance. Network analysis demonstrated a more complex bacterial network structure in the hydrolysis ponds compared to the aeration ponds. Furthermore, enzyme gene abundance revealed higher metabolic enzyme genes in the hydrolysis ponds, while signal transduction enzyme genes were more abundant in the aeration ponds. Notably, the top 10 bacterial genera, primarily Hydromonas in the hydrolysis ponds and Ferruginibacter in the aeration ponds, exhibited distinct contributions to signal transduction enzyme genes. Hydromonas dominated the metabolic enzyme genes in both ponds. These findings provide crucial insights for optimizing dairy wastewater treatment technologies.
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Bactérias , Reatores Biológicos , Indústria de Laticínios , RNA Ribossômico 16S , Águas Residuárias , Águas Residuárias/microbiologia , Bactérias/genética , Bactérias/enzimologia , Bactérias/classificação , Bactérias/metabolismo , Reatores Biológicos/microbiologia , Hidrólise , RNA Ribossômico 16S/genética , Purificação da Água , Biofilmes/crescimento & desenvolvimento , Eliminação de Resíduos Líquidos/métodosRESUMO
OBJECTIVES: This study evaluated the expression and significance of SNHG3 in Rheumatoid arthritis (RA) aiming to explore a biomarker and regulator for RA. METHODS: The expression of SNHG3 in serum and synovial tissue was compared between RA patients and healthy individuals using PCR. The RA animal models were induced by the porcine type II collagen with Wistar rats and validated by the foot volume and AI score. The human fibroblast-like synoviocytes (H-FLS) were treated with LPS to mimic the injury during RA onset and the cell growth was assessed by CCK8 assay. RESULTS: SNHG3 was significantly downregulated in the serum and synovial tissue of RA patients compared with healthy individuals. Downregulated SNHG3 could discriminate RA patients from healthy individuals with high sensitivity (0.875) and specificity (0.844). Porcine type II collagen induced increasing foot volume and AI scores of rats and SNHG3 was downregulated in RA rats. In LPS-induced H-FLS, SNHG3 negatively regulated miR-128-3p, and the alleviated effect of SNHG3 overexpression on cellular inflammation and oxidative stress was reversed by miR-128-3p upregulation. CONCLUSIONS: Serum SNHG3 was considered a potential diagnostic biomarker for RA from healthy individuals. SNHG3 regulated inflammatory response and oxidative stress via negatively modulating miR-128-3p.
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Electron spins in van der Waals materials are playing a crucial role in recent advances in condensed-matter physics and spintronics. However, nuclear spins in van der Waals materials remain an unexplored quantum resource. Here we report optical polarization and coherent control of nuclear spins in a van der Waals material at room temperature. We use negatively charged boron vacancy ([Formula: see text]) spin defects in hexagonal boron nitride to polarize nearby nitrogen nuclear spins. We observe the Rabi frequency of nuclear spins at the excited-state level anti-crossing of [Formula: see text] defects to be 350 times larger than that of an isolated nucleus, and demonstrate fast coherent control of nuclear spins. Further, we detect strong electron-mediated nuclear-nuclear spin coupling that is five orders of magnitude larger than the direct nuclear-spin dipolar coupling, enabling multi-qubit operations. Our work opens new avenues for the manipulation of nuclear spins in van der Waals materials for quantum information science and technology.
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PURPOSE: To analyze the clinical values of echocardiography combined with vascular ultrasound in the diagnosis of aortic dissection according to the DeBakey classification. METHODS: The clinical data of 77 patients with aortic dissection admitted to our hospital from August 2016 to January 2022 were retrospectively analyzed. All patients were examined with ultrasound and CT angiography (CTA), the consistency between ultrasound and CTA ± intraoperative diagnosis for the classification of AD was checked, as well as the differences in ultrasound signs and Ultrasound parameters between different types of AD were analyzed. RESULTS: The results of Kappa value: There was a high level of agreement between echocardiography combined with transabdominal vascular ultrasound and CTA ± intraoperative diagnosis for the classification of AD (Kappa = 0.897, p = 0.000). In the ultrasound signs, the proportion of pericardial effusion, aortic regurgitation, aortic widening, and coronary artery involvement in type DeBakey I and II aortic dissection was significantly higher than that in Type III. There was no significant difference in the proportion of intimal floating, true and false lumen, and intimal rupture in Types I, II, and III aortic dissections. In the comparison of ultrasound parameters, there is a statistically significant difference in the values of LAD (left atrial diameter), LAV (left atrial volume), and LVEDD (left ventricular end-diastolic diameter) among different types of aortic dissection. There is no significant difference in IVS (interventricular septum thickness), LVPW (left ventricular posterior wall thickness), LVEF (left ventricular ejection fraction), and E/e' ratio among different types of aortic dissection. CONCLUSION: Echocardiography combined with transabdominal vascular ultrasound can accurately evaluate aortic dissection with real-time dynamic images and provide important clinical significance for early individualized treatment of patients through accurate classification of different aortic dissection.
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Dissecção Aórtica , Função Ventricular Esquerda , Humanos , Volume Sistólico , Estudos Retrospectivos , Dissecção Aórtica/diagnóstico por imagem , EcocardiografiaRESUMO
Long-standing inflammatory bowel disease predisposes to the development of colorectal cancer (CRC). Interleukin (IL) -6, a pivotal link between chronic inflammation and tumor progression, has recently been recognized as a potential therapeutic target. The effect of IL-6 on proliferation and metastasis of CRC by activating the STAT3 pathway has been widely demonstrated in recent years, but few on mediating tumor immune evasion. In this study, we found that IL-6 was remarkably overexpressed in CRC and its elevation was associated with a poor prognosis. We studied CRC tumorigenesis in vivo by inoculating MC38 tumors and induced-CRC model via AOM/DSS (azoxymethane/dextransulfate sodium) in IL-6 deficient (IL-6-/-) and wild-type (WT) mice and found that IL-6-/- mice were less susceptible to develop tumors, compared to WT mice. We detected CD8+ T cells via immunofluorescence and found they exhibit high expression in tumor of IL-6-/- mice. High level of IL-6 was found in colitis model, with down-regulation of MHC-I molecules. In in vitro experiments, we found that IL-6 may act as a negative regulator in IFNγ-STAT1-MHC-I signaling. In addition, vivo trials also confirmed that MHC-I mRNA level was negatively related to the existence of IL-6. Furthermore, the blockade of IL-6 also activated CD8+T-cell accumulation and led to the high PD-L1 expression in CRC, which can sensitize animals to anti-PD-1 therapy. Our study provides a research basis for the significant role of IL-6 in tumor evasion and highlights a novel target to improve the efficacy of immunotherapy.
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Neoplasias Colorretais , Interleucina-6/metabolismo , Animais , Linfócitos T CD8-Positivos/metabolismo , Neoplasias Colorretais/metabolismo , Imunoterapia , Camundongos , Transdução de Sinais , Evasão TumoralRESUMO
AIMS: Greenhouses are widely used in agriculture systems to shield crops from unfavourable weather to achieve a year-round food supply. In recent years, aquaculture ponds have been placed in greenhouses in many regions. The impacts of the greenhouses on planktonic bacterial communities should be uncovered. METHODS AND RESULTS: In this study, two polyolefin film greenhouses accommodating aquaculture ponds were established and planktonic bacterial communities were compared from samples taken in aquaculture ponds inside and outside the greenhouses, using Illumina 16S rRNA sequencing. CONCLUSIONS: The results showed there were significant variations in bacterial community structure between indoor and outdoor samples. Obvious differences were also found between two greenhouses, whereas the differences in indoor samples were weaker than outdoor samples. Significantly higher temperature (in summer), pH and permanganate index were found in the outdoor pond samples. Results of redundancy analysis showed that Proteobacteria and Bacteroidota were positively related to the dissolved oxygen, total nitrogen and total phosphorus, and Actinobacteriota were positively related to pH, temperature and permanganate index, whereas Cyanobacteria were positively related to the salinity, conductivity, total dissolved solids and ammonia nitrogen. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study revealed that greenhouses significantly influenced planktonic bacterial communities in aquaculture ponds. This study is expected to provide a scientific basis for aquaculture in greenhouses.
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Aquicultura , Plâncton , Bactérias/genética , Plâncton/genética , Lagoas/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
INTRODUCTION: To compare the macular retinal vessel density(VD) of diabetics with high myopia, diabetics without high myopia and healthy controls. METHODS: This cross-sectional study recruited type 2 diabetic (T2D) people with no history of ocular treatment in our hospital. Thirty T2D people with high myopia (30 eyes) were included in group A, while 30 T2D people (30 eyes) without myopia were included in group B. Another healthy volunteers (30 eyes) were included in group C. The superficial and deep capillary plexuses VD of macular were measured in all subjects by optical coherence tomography angiography (OCTA). In T2D people with high myopia, the correlation between VD in macular regions and baseline data was investigated. RESULTS: â Overall comparison of the 3 groups: No statistically significant differences in macular central superficial vessel density (SVD) were found in the three groupsï¼P > 0.05). There were significant differences in the temporal, superior, nasal, inferior SVD between the 3 groups (P < 0.05). There were significant differences in macular central, temporal, superior, nasal, and inferior deep vessel density (DVD) between the three groups (P < 0.05). â¡ Comparison of B (no myopia, T2D group) and C (healthy control group): Inferior SVD in group B was lower than that in group C (P < 0.05). Temporal, superior, nasal, and inferior DVD in group B were lower than those in group C (P < 0.05). ⢠A (high myopia group, T2D) compared with B (no myopia, T2D group), A group compared with C (healthy control group): Temporal, superior, nasal, inferior SVD and DVD in group A were all lower than those in group B and C (P < 0.05), DVD in group B were lower than those in group C (P < 0.05). ⣠The mean SVD and DVD were not correlated with age, IOP , anterior chamber depth, corneal curvature but they were negatively correlated with axial length and duration of diabetes in the T2D people with high myopia. CONCLUSION: Myopia and diabetes are two important factors affecting macular retinal vessel density. Comparing with the eyes of T2D people without high myopia, the VD in macular regions shows a higher decline in the eyes of T2D people with high myopia.
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BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is widely used for clinical treatment of advanced cancers. However, the regulatory mechanism underlying precise hyperthermia treatment in advanced gastric cancer (AGC) remains unclear. MiR-409-3p is reportedly downregulated in a variety of cancers, although its role in regulating treatment of AGC by precise hyperthermia remains unclear. The underlying mechanisms of miRNA-medicated regulation have been investigated using predicted and validated miRNA-gene targets, confirming the role of miRNA in HIPEC; METHODS: We used quantitative real time PCR (qRT-PCR) to detect miR-409-3p expression in gastric cancer (GC), as well as adjacent normal tissues, following exposure to varying temperatures. We detected miR-409-3p targets using dual-luciferase assay, then performed cell apoptosis, western blotting, invasion, and migration assays to detect GC functions; RESULTS: MiR-409-3p was upregulated and downregulated in precise hyperthermia and AGC, respectively. Moreover, miR-409-3p upregulated the Krüppel-like-factor 17 (KLF17), which subsequently inhibited migration, invasiveness, and epithelial-mesenchymal transition (EMT) but promoted apoptosis in GC cells; CONCLUSIONS: Precise hyperthermia upregulated miR-409-3p and KLF17 indirectly, thereby inhibiting invasion, migration, and EMT, and promoting apoptosis of gastric cancer cells.
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Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Hipertermia Induzida , MicroRNAs/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Fatores de Transcrição/metabolismo , Apoptose/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Regulação para Cima/genética , Vimentina/metabolismoRESUMO
BACKGROUND: Long non-coding RNAs (LncRNAs) are dysregulated in multiple human cancers and they are highly involved in tumor progression. Previous studies have identified the oncogenic lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in human cancers, while its roles in cervical cancer (CC) remain unclear. Herein we intended to characterize the implication of HOXD-AS1 in CC. METHODS: qRT-PCR was applied to examine the relative expression of HOXD-AS1 in CC tissues, cell lines and transfected cells. Wound healing and transwell assays were applied to detect cell migration and invasion alteration. The targeting relationship between miRNA and mRNA/lncRNA was determined by dual luciferase reporter, qRT-PCR and western blot assays. RESULTS: HOXD-AS1 was overexpressed in CC tissues and cell lines. Its higher level predicted worse prognosis of CC patients. SiRNA mediated knockdown of HOXD-AS1 repressed CC cell migration and invasion, and its overexpression did the opposite. Mechanistically, HOXD-AS1 acted as a competing endogenous RNA (ceRNA) to sponge miR-877-3p and led to upregulation of FGF2, a target of miR-877-3p. Importantly, either miR-877-3p overexpression or FGF2 inhibition could abolish the migration and invasion promotion induced by HOXD-AS1. CONCLUSION: HOXD-AS1 functions as a tumor-promoting lncRNA via the miR-877-3p/FGF2 axis in CC. HOXD-AS1 might be a promising therapeutic target as well as a novel prognostic biomarker for CC.
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Fator 2 de Crescimento de Fibroblastos/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ligação Competitiva , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Feminino , Fator 2 de Crescimento de Fibroblastos/biossíntese , Fator 2 de Crescimento de Fibroblastos/genética , Células HeLa , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Prognóstico , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genéticaRESUMO
BACKGROUND: To investigate the effects of 0.05% povidone-iodine (PI) irrigation on the ocular surface structure and bacterial survival rate in patients with cataract. METHODS: Ninety eyes of 90 patients with cataract were included. Before surgery, the operative field was irrigated with 0.05% PI and divided into 30-s, 1-, and 2-min groups. Anterior chamber fluid was cultured bacteriologically. Tear film breakup time (BUT), corneal fluorescein staining (CFS), lacrimal river height (LRH), and Schirmer test I (STI) were conducted to assess ocular surface. RESULTS: In all groups, the patients had significantly shorter postoperative BUT at 1 day, 3 days, and 1 week postoperatively than preoperatively. In addition, there was still lower BUT at 1 month postoperatively in the 1- and 2-min groups. STI and LRH were all decreased postoperatively at different time points (1 day, 3 days, 1 week), while CFS was increased. With the extension of time preoperatively (1 and 3 months), the ocular surface indicators returned to the preoperative level. The bacterial cultures after eye irrigating were negative in all groups. CONCLUSION: 0.05% PI irrigating the conjunctival sac for 30 s can achieve a low bacterial contamination rate. Importantly, it reduced the damage of ocular surface, which is beneficial to the recovery of ocular surface function.
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Anti-Infecciosos Locais/uso terapêutico , Extração de Catarata/métodos , Doenças da Córnea/prevenção & controle , Infecções Oculares Bacterianas/prevenção & controle , Povidona-Iodo/uso terapêutico , Irrigação Terapêutica/métodos , Idoso , Idoso de 80 Anos ou mais , Córnea/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lágrimas/metabolismoRESUMO
BACKGROUND: This study sought to report the outcomes of a combined cataract extraction, intraocular lens (IOL) insertion and micro-incision vitrectomy (MIVS) procedure for the treatment of Behcet uveitis. METHODS: This investigation involved the retrospective evaluation of a case series of patients with Behcet uveitis who underwent cataract extraction, IOL insertion and MIVS in a single surgical session at the same institution between January 2013 and November 2016. Outcome measures included visual acuity, inflammatory reaction, systemic anti-inflammatory medications, intraocular pressure (IOP) and complications. RESULTS: Seven eyes of seven patients with a mean age of 39.00 ± 5.54 years (range, 32 to 48 years) and a mean follow-up duration of 13.57 ± 5.83 months (range, 6 to 24 months) were studied; five patients with a history of well-controlled uveitis were included. All patients underwent cataract extraction and IOL implantation combined with MIVS. All patients received postoperative steroids, which were slowly tapered during the weeks after surgery. There were no significant complications related to the surgery. Overall, best-corrected visual acuity (BCVA) was improved from log MAR (logarithm of the minimum angle of resolution) 1.67 ± 0.67 preoperatively to log MAR 0.74 ± 0.35 postoperatively; this improvement was statistically significant (p < 0.05). All eyes were deemed quiet at follow-up, and no patients required the escalation of therapy for long-term uveitis control. CONCLUSIONS: This retrospective series indicates that a procedure that combines phacoemulsification, IOL implantation and MIVS is a feasible technique for the removal of cataracts and pathologic vitreous in eyes with Behcet uveitis. This approach can restore vision without obvious complications.
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Síndrome de Behçet/complicações , Extração de Catarata , Implante de Lente Intraocular , Uveíte/cirurgia , Vitrectomia/métodos , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Pressão Intraocular , Implante de Lente Intraocular/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Acuidade VisualRESUMO
The purpose of this study was to investigate the role of oncostatin M (OSM) in tubulointerstitial lesion (TIL) in lupus nephritis (LN). We found that OSM was highly expressed in the renal tissue of LN mice. OSM is one of the interleukin-6 cytokine family members. In order to clarify the role and mechanism of OSM in LN, mice with LN were treated with anti-OSM antibody or isotype antibody. We evaluated the tubular epithelial-mesenchymal transdifferentiation (EMT) by detecting the E-cadherin, α-smooth muscle actin (α-SMA), and fibronectin (FN) expression. We analyzed the inflammation by observing the monocyte chemotactic factor-1 (MCP-1) and intercellular adhesion molecule (ICAM-1) expression and calculated the tubulointerstitial fibrosis area by Masson staining. The results showed that anti-OSM antibody, rather than isotype antibody, improved EMT, inflammation, and tubulointerstitial fibrosis. In addition, the signal transducer and activator of transcription (STAT) 1 and STAT3 signaling was activated by tyrosine phosphorylation in LN mouse renal tissue, indicating that the phosphorylated STAT1 (p-STAT1) and p-STAT3 were involved in kidney injury. Moreover, decreased p-STAT3 instead of p-STAT1 has been observed after anti-OSM antibody injection. Thus, we concluded that OSM is associated with TIL in lupus nephritis, which may be connected with the activation of STAT3 rather than that of STAT1.
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Anticorpos/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Oncostatina M/metabolismo , Animais , Anticorpos/imunologia , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Isotipos de Imunoglobulinas/imunologia , Isotipos de Imunoglobulinas/uso terapêutico , Molécula 1 de Adesão Intercelular/metabolismo , Nefrite Lúpica/metabolismo , Camundongos , Oncostatina M/antagonistas & inibidores , Oncostatina M/imunologia , Fosforilação/efeitos dos fármacos , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of tumor and is associated with high morbidity and mortality rates. Patients with HCC routinely undergo surgery followed by adjuvant radiation therapy and chemotherapy. Despite such aggressive treatment approaches, median survival times remain under 1 year in most cases. KDM5C is a member of the family of JmjC domain-containing proteins that removes methyl residues from methylated lysine 4 on histone H3 lysine 4 (H3K4). KDM5C has been proposed as an oncogene in many types of tumors; however, its role and underlying mechanisms in HCC remain unclear. METHODS: Expression level of KDM5C was examined by RT-PCR, and IHC. Forced expression of KDM5C was mediated by retroviruses, and KDM5C was downregulated by shRNAs expressing lentiviruses. Migration and invasion of HCC cells was measured by wound healing, Transwell and Matrigel assays respectively. RESULTS: In this study, we report that KDM5C is abundantly expressed in invasive human HCC cells. Cellular depletion of KDM5C by shRNA inhibited HCC cell migration, invasion and epithelial-mesenchymal transition in vitro, and markedly decreased the metastasis capacity of invasive HCC cells in the liver and lung. Furthermore, ectopic expression of KDM5C in HCC cells promoted cell migration, invasion and epithelial-mesenchymal transition via the inactivation of BMP7. Knockdown of BMP7 significantly promotes shKDM5C-induced cell migration inhibition. CONCLUSIONS: Taken together, these data suggest that KDM5C-mediated BMP7 inactivation is essential for HCC cell invasion.
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Proteína Morfogenética Óssea 7/antagonistas & inibidores , Proteína Morfogenética Óssea 7/biossíntese , Carcinoma Hepatocelular/metabolismo , Histona Desmetilases/biossíntese , Neoplasias Hepáticas/metabolismo , Adulto , Animais , Proteína Morfogenética Óssea 7/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologiaRESUMO
A specific, sensitive and accurate analytical LC-MS/MS assay was developed for the simultaneous determination of two steroidal glycosides, tenacissoside H and tenacissoside I, in rat plasma. An Agilent ZORBAX SB-C18 column was used with an isocratic mobile phase system composed of methanol-water-formic acid (70:30:0.1, v/v/v) at a flow rate of 0.3 mL/min. The analysis was performed on a positive ionization electrospray mass spectrometer via selected reaction monitoring mode scan. One-step protein precipitation with acetonitrile was chosen to extract the analytes from plasma. The lower limits of quantification were 0.9 ng/mL for tenacissoside H and tenacissoside I. The intra- and inter-day precisions were 2.03-11.56 and 3.76-11.62%, respectively, and the accuracies were <110.28% at all quality control levels. The validated method was applied to a pharmacokinetic study in rats after oral gavage of Marsdenia tenacissima extract.
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Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacocinética , Glicosídeos/sangue , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Glicosídeos/administração & dosagem , Glicosídeos/farmacocinética , Masculino , Marsdenia , Ratos , Ratos Sprague-DawleyRESUMO
Marine aquaculture is key for protein production but disrupts marine ecosystems by releasing excess feed and pharmaceuticals, thus affecting marine microbes. Though vital, its environmental impact often remains overlooked. This article delves into mariculture's effects on marine microbes, including bacteria, fungi, viruses, and antibiotic-resistance genes in seawater and sediments. It highlights how different mariculture practices-open, pond, and cage culture-affect these microbial communities. Mariculture's release of nutrients, antibiotics, and heavy metals alters the microbial composition, diversity, and functions. Integrated multi-trophic aquaculture, a promising sustainable approach, is still developing and needs refinement. A deep understanding of mariculture's impact on microbial ecosystems is crucial to minimize pollution and foster sustainable practices, paving the way for the industry's sustainable advancement.
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Resource-based cities are important strategic bases for securing resources in China and have made great contributions to the country's economic development. Long-term extensive resource development has made resource-based cities an important region constraining China from achieving comprehensive low-carbon development. Therefore, it is of great significance to explore the low-carbon transition path of resource-based cities for their energy greening, industrial transformation, and high-quality economic development. This study compiled the CO2 emission inventory of resource-based cities in China from 2005 to 2017, explored the contribution to CO2 emissions from three perspectives (driver, industry, and city), and predicted the peak of CO2 emissions in resource-based cities. The results show that resource-based cities contribute 18.4% of the country's GDP and emit 44.4% of the country's CO2 and that economic growth and CO2 emissions have not yet been decoupled. The per capita CO2 emissions and emission intensity of resource-based cities are 1.8 times and 2.4 times higher than the national average, respectively. Economic growth and energy intensity are the biggest drivers and main inhibitors of CO2 emissions growth. Industrial restructuring has become the biggest inhibitor of CO2 emissions growth. Based on the different resource endowments, industrial structures, and socio-economic development levels of resource-based cities, we propose differentiated low-carbon transition pathways. This study can provide references for cities to develop differentiated low-carbon development paths under the "double carbon" target.
Assuntos
Dióxido de Carbono , Carbono , Carbono/análise , Cidades , Dióxido de Carbono/análise , Objetivos , China , Desenvolvimento EconômicoRESUMO
The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict the concentrations of encapsulated and free doxorubicin in plasma and tissues in mice after intravenous injection of PEGylated liposomes (Doxil®). The PBPK model used in this study contains liposomes and free doxorubicin disposition components. The free doxorubicin disposition component was used to simulate the disposition of free doxorubicin produced by mononuclear phagocyte system (MPS)-degrading liposomes. The liver, spleen, kidneys, and lungs contain an additional MPS subcompartment. These compartments are interconnected through blood and lymphatic circulation. The model was validated strictly by four doses of external observed plasma and tissue concentration-time profiles. The fold error (FE) values were almost all within threefold. The sensitivity analysis revealed that the MPS-related parameters greatly influenced the model. The predicted in vivo distribution characteristics of the doxorubicin liposomes and doxorubicin solution were consistent with the observed values. The PBPK model was established based on the physiological mechanism and parameters of practical significance that can be measured in vitro. Thus, it can be used to study the pharmacokinetic properties of liposomes. This study also provides a reference for the establishment of liposome PBPK model.