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Skin wound infection has become a global clinical problem in recent years. Curcumin (Cur) and polylysine (PLL) are natural products with strong antibacterial properties. However, the poor water solubility and low stability of Cur and the cationic toxicity of PLL limit their application. In this study, we synthesized a macromolecular hyaluronic acid (HA)-curcumin drug (HC) via esterification. HC was attracted by electrostatic interactions with positively charged PLL to form a spherical nanocomplex (HCP) with hyaluronidase (HAase) and pH dual response under ultrasonication. HCP was found to target the bacterial infection microenvironment and release Cur and PLL for synergistic antibacterial action. In addition, HCP was proven to exhibit good biocompatibility and broad spectrum antibacterial activity to bacterial strains S. aureus and E. coli and antibacterial biofilm activities in vitro. In vivo experiments showed that HCP could inhibit pathogens and promote wound healing. These results prove that HCP can be used as a new strategy for the treatment and management of infected wounds.
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Background: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease and has a high mortality rate. Currently, no effective treatments are available to reduce the progression of kidney damage associated with diabetes. Objectives: To explore the influence and predictive value of the atherogenic index of plasma (AIP) on early chronic kidney disease and liver injury in patients with type 2 diabetes mellitus (T2DM). Methods: Medical records of 1057 hospitalized adult patients with T2DM between January 2021 and December 2022 were collected. The predictive value of AIP, renal function, and liver injury in patients with T2DM were analyzed using Pearson's correlation, multiple logistic regression, and receiver operating characteristic (ROC) curve analyses. Results: AIP was a sensitive indicator of early liver and kidney injury in patients with T2DM. Patients in the DKD group showed increased AIP that positively correlated with serum creatinine, uric acid, and ß2-microglobulin levels. Increased AIP negatively correlated with estimated glomerular filtration rate (eGFR). AIP significantly correlated with alanine aminotransferase and aspartate aminotransferase levels and glutamyl transpeptidase-to-platelet ratio (GPR). An eGFR of 60-100 mL/min/1.73 m2 significantly increased the risk of DKD as the AIP increased. At lower GPR levels, the risk of DKD significantly increased with increasing AIP. However, no significant difference was found between the 2 groups when the GPR was >0.1407. The ROC curve analysis showed that AIP could predict early liver injury. Conclusions: AIP is directly involved in early liver and kidney injury in T2DM and may be a sensitive indicator for early detection.
Diabetes and its complications are a global public health concern. Diabetic kidney disease (DKD) is the main cause of end-stage renal disease, and metabolism-related disease factors are found throughout the progression of DKD. This study identified common sensitive indicators of early metabolism-related damage to liver and kidney function in patients with T2DM.
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The aggregation of graphene oxide (GO) during the hydration process limits its wide application. Polymer superplasticizers have been used to improve the dispersion state of GO due to their adsorption and site-blocking effects, though the formation of a large amount of foam during the mixing process weakens the mechanical properties of cement. A highly dispersed amphoteric polycarboxylate superplasticizer-stabilized graphene oxide (APC/GO) toughening agent was prepared by electrostatic self-assembly. Results demonstrate that the APC/GO composite dispersed well in a cement pore solution due to the steric effect offered by the APC. Additionally, the well-dispersed GO acted as an antifoaming agent in the cement since GO nanosheets can be absorbed at the air-liquid interface of APC foam via electrostatic interactions and eliminate the air-entraining effect. The well-dispersed APC/GO sheets promoted cement hydration and further refined its pore structure owing to the nucleation effect. The flexural and compressive strength of the cement containing the APC/GO composite were enhanced by 21.51% and 18.58%, respectively, after a 7-day hydration process compared with a blank sample. The improved hydration degree, highly polymerized C-S-H gel, and refined pore structure provided enhanced mechanical properties.
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BACKGROUNDS: The efficacy of endoscopic submucosal dissection (ESD) to treat poorly differentiated superficial esophageal squamous cell carcinoma (SESCC) is unclear. AIMS: To exploring the efficacy and prognosis of ESD treatment poorly differentiated SESCC compared with esophagectomy. METHODS: A retrospective cohort study was conducted, the data of poorly differentiated SESCC patients who received ESD or esophagectomy from Jan 2011 to Jan 2021 were analyzed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and procedure-related variables were compared between ESD and esophagectomy group. RESULTS: 95 patients underwent ESD, while 86 underwent esophagectomy. No significant differences were found between the two groups in OS (P = 0.587), DSS (P = 0.172), and RFS (P = 0.111). Oncologic outcomes were also similar between the two groups in propensity score-matched analysis. For T1a ESCC, the rates of R0 resection, LVI or nodal metastasis and additional therapy were similar between ESD and esophagectomy groups. But for T1b ESCC, the rates of positive resection margin and additional therapy were significantly higher in ESD group than those in esophagectomy group. CONCLUSIONS: ESD is a minimally invasive procedure that has comparable oncologic outcomes with esophagectomy for treatment poorly differentiated T1a ESCC. However, ESD is not suitable for poorly differentiated T1b ESCC, additional surgery or radiochemotherapy should be required.
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A highly enantioselective 1,3-dipolar cycloaddition of ethoxyformylmethylene oxindole with iminoesters has been achieved using the Cu(I)-(S,Sp)-Ph Phosferrox catalytic system, generating a series of chiral spiro[pyrrolidin-3,3'-oxindole] compounds with four consecutive stereocenters, including a spirocycle quaternary center (71%-99% yield, up to >20:1 dr and 95:5 er). The compounds exhibited good inhibitory activity against Valsa mali (V.m.), Fusarium oxysporium (F.o.), and Alternaria brassicae (A.b.).
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Lung cancer remains one of the leading causes of cancer-related mortality worldwide necessitating the development of innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents a promising advancement in the field of oncology offering a novel approach to target and eliminate tumor cells with high specificity and reduced risk of immune-related adverse effects. This paper reviews the mechanism, potential targets, and recent advances in CAR-NK cell therapy for lung cancer, including the design and engineering of CAR-NK cells, preclinical studies, and the outcomes of early-phase clinical trials. We highlight the unique advantages of using NK cells, such as their innate ability to recognize and kill cancer cells and their reduced potential for inducing graft-versus-host disease (GvHD) and cytokine release syndrome (CRS) compared to CAR T-cell therapies. Results from recent studies demonstrate significant antitumor activity in lung cancer models with improved targeting and persistence of CAR-NK cells observed in vitro and in vivo. Finally, we discuss the challenges in optimizing CAR-NK cell therapies, including the potential resistance mechanisms. The paper concludes with an outlook on the future directions of CAR-NK cell research and its implications for lung cancer treatment emphasizing the importance of continued innovation and collaboration in the field.
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Background: Papillary renal neoplasm with reverse polarity (PRNRP) is a novel entity with unique clinicopathological characteristics, and only a small number of patients with PRNRP have been described. Methods: We retrospectively analyzed the data for nine patients with PRNRP and evaluated differences in the clinical, histomorphological, immunohistochemical, and molecular features; prognosis; and differential diagnosis of PRNRP from other renal tumors with papillary structure. Results: There were six males and three females aged 36 to 74 years (mean: 62.33 years; median: 68 years). All the tumors were solitary and ranged from 1 to 3.7 cm (mean: 2.17 cm; median: 2 cm), with three and six tumors arose in the left and right renal tract, respectively. Pathologically, PRNRP is a small, well-circumscribed neoplasm with predominant papillary formations. The lining epithelium is composed of a monolayer of cuboidal to low-columnar cells with low-grade nuclei arranged against the apical pole of the tumor cells. Edema, mucinous degeneration, and hyaline degeneration are found in the fibrovascular cores. Foamy macrophages, psammoma bodies, hemosiderin deposition, and infiltrative tumor boundaries were present in some patients. Immunohistochemically, all tumors showed diffuse positive staining for GATA3. Sanger sequencing confirmed the presence of KRAS mutation in seven patients. All patients had a good prognosis after surgery and were relapse free. Positive staining for GATA3 and negative staining for vimentin were the most significant markers for differentiating PRNRP from other renal tumors with analogous structure. Conclusions: These findings suggested that PRNRP is a distinctive subtype of renal tumor with specific pathological features and indolent behaviors that should be distinguished from other renal tumors, especially papillary renal cell carcinoma. A monolayer of tumor cells with an inverted nuclear pattern, positive staining for GATA3, and KRAS mutation are essential for pathological diagnosis. Owing to its satisfactory prognosis, the surveillance and follow-up of patients with PRNRP should be additionally formulated.
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Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound 4d exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against Helminthosporium maydis, Trichothecium roseum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Alternaria brassicae, Alternaria alternate, and Fusarium solan (MICs: 8-32 µg/mL). Compound 4k also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including Fusarium oxysporium f. sp. niveum and Mycosphaerella melonis (MICs: 8-32 µg/mL). The preliminary structure-activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.
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Antifúngicos , Benzopiranos , Fungicidas Industriales , Nitrilos , Oxindoles , Piperazinas , Compuestos de Espiro , Antifúngicos/química , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Fungicidas Industriales/farmacologíaRESUMEN
The effects of environmental radiofrequency electromagnetic fields (RF-EMF) on embryonic neural stem cells have not been determined, particularly at the proteomic level. This study aims to elucidate the effects of environmental levels of RF-EMF radiation on embryonic neural stem cells. Neuroectodermal stem cells (NE-4C cells) were randomly divided into a sham group and an RF group, which were sham-exposed and continuously exposed to a 1950 MHz RF-EMF at 2 W/kg for 48 h. After exposure, cell proliferation was determined by a Cell Counting Kit-8 (CCK8) assay, the cell cycle distribution and apoptosis were measured by flow cytometry, protein abundance was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and mRNA expression was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We did not detect differences in cell proliferation, cell cycle distribution, and apoptosis between the two groups. However, we detected differences in the abundance of 23 proteins between the two groups, and some of these differences were consistent with alterations in transcript levels determined by qRT-PCR (P < 0.05). A bioinformatics analysis indicated that the differentially regulated proteins were mainly enriched in 'localization' in the cellular process category; however, no significant pathway alterations in NE-4C cells were detected. We conclude that under the experimental conditions, low-level RF-EMF exposure was not neurotoxic but could induce minor changes in the abundance of some proteins involved in neurodevelopment or brain function.
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Campos Electromagnéticos , Células-Madre Neurales , Campos Electromagnéticos/efectos adversos , Cromatografía Liquida , Proteómica , Espectrometría de Masas en Tándem , Ondas de Radio/efectos adversosRESUMEN
Images captured in low light conditions suffer from low visibility, blurred details and strong noise, resulting in unpleasant visual appearance and poor performance of high level visual tasks. To address these problems, existing approaches have attempted to enhance the visibility of low-light images using convolutional neural networks (CNN). However, due to the insufficient consideration of the characteristics of the information of different frequency layers in the image, most of them yield blurry details and amplified noise. In this work, to fully extract and utilize these information, we proposed a novel Adaptive Frequency Decomposition Network (AFDNet) for low-light image enhancement. An Adaptive Frequency Decomposition (AFD) module is designed to adaptively extract low and high frequency information of different granularities. Specifically, the low-frequency information is employed for contrast enhancement and noise suppression in low-scale space and high-frequency information is for detail restoration in high-scale space. Meanwhile, a new frequency loss function are proposed to guarantee AFDNet's recovery capability for different frequency information. Extensive experiments on various publicly available datasets show that AFDNet outperforms the existing state-of-the-art methods both quantitatively and visually. In addition, our results showed that the performance of the face detection can be effectively improved by using AFDNet as pre-processing.
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The Mannich reaction is commonly used to introduce N atoms into compound molecules and is thus widely applied in drug synthesis. The Mannich reaction accounts for a certain proportion of structural modifications of natural products. The introduction of Mannich bases can significantly improve the activity, hydrophilicity, and medicinal properties of compounds; therefore, the Mannich reaction is widely used for the structural modification of natural products. In this paper, the application of the Mannich reaction to the structural modification of natural products is reviewed, providing a method for the structural modification of natural products.
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Productos Biológicos , Productos Biológicos/farmacología , Bases de Mannich/químicaRESUMEN
This research aims to investigate the synergistic reinforcing mechanisms of chemically combined graphene oxide and nanosilica (GO-NS) in the structure of calcium silicate hydrate (C-S-H) gels compared with physically combined GO/NS. The results confirmed that the NS chemically deposited on the GO surface formed a coating to keep GO from aggregation, while the connection between GO and NS in GO/NS was too weak to prevent GO from clumping, making GO-NS better dispersed than GO/NS in pore solution. When applied to cement composites, the incorporation of GO-NS enhanced the compressive strength by 27.3% after 1-day hydration compared to that of the plain sample. This is because that GO-NS generated multiple nucleation sites at early hydration, reduced the orientation index of calcium hydroxide (CH), and increased the polymerization degree of C-S-H gels. GO-NS acted as the platforms for the growing process of C-S-H, enhancing its interface bonding strength with C-S-H and increasing the connection degree of the silica chain. Furthermore, the well-dispersed GO-NS was prone to insert in C-S-H and induced deeper cross-linking, thereby refining the microstructure of C-S-H. All these effects on hydration products resulted in the mechanical improvement of cement.
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BACKGROUND Patients with insulin-resistant diabetes have the highest risk of kidney disease. The triglyceride glucose (TyG) index is considered a reliable and simple marker of insulin resistance. We studied the relationship between the TyG index, diabetic kidney disease (DKD), and related metabolic disorders in patients with type 2 diabetes. MATERIAL AND METHODS This retrospective study included a consecutive case series from January 2021 to October 2022 in the Department of Endocrinology at Hebei Yiling Hospital. In total, 673 patients with type 2 diabetes met the inclusion criteria. The TyG index was calculated by napierian logarithmic (ln) (fasting triglyceride×fasting glucose /2). Patient demographic and clinical indicators were obtained from medical records, and statistical analysis was conducted using SPSS version 23. RESULTS The TyG index was significantly related to metabolic indicators (low-density lipoprotein, high-density lipoprotein, alanine aminotransferase, plasma albumin, serum uric acid, triglyceride, and fasting glucose) and urine albumin (P<0.01) but not with serum creatinine and estimated glomerular filtration rate. In multiple regression analysis, an increase in the TyG index was revealed to be an independent risk factor for DKD (OR: 1.699, P<0.001). CONCLUSIONS The TyG index was independently related to DKD and related metabolic disorders; therefore, the TyG index can be used as an early sensitive target for clinical guidance in the treatment of DKD with insulin resistance.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Resistencia a la Insulina , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Glucosa , Estudios Retrospectivos , Triglicéridos , Ácido Úrico , Glucemia/metabolismo , Biomarcadores , Factores de RiesgoRESUMEN
PURPOSE: Intestinal injury commonly occurs in radiation therapy, but its pathogenesis is not well understood. The relationship between irradiation-induced intestinal injury and bile acids (BAs) metabolism remains elusive. This study intends to clarify the role of BAs metabolism in irradiation-induced intestinal injury and the potential for supplementation with BAs to alleviate this injury. MATERIALS AND METHODS: BAs metabolomic analysis of fecal pellets from normal and 12 Gy γ-ray total abdominal irradiation (TAI) treated mice was performed. The effects of a crude bile extract (BAmix) or lithocholic acid (LCA) on mice exposed to 12 Gy γ-ray TAI were determined by analyzing weight loss, colon length, villus length, crypt number, and the expression of leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and yes-associated protein 1 (YAP1). The effects of BAmix or LCA on intestinal organoids after 4 Gy irradiation were analyzed. ELISA assay was applied to test IL-1ß, IL-6 and TNF-α levels in mouse intestine. The expression changes of G protein-coupled receptor 1 (TGR5) and YAP1 in the colonic mucosa of patients with radiation-induced intestinal injury were determined by IHC. RESULTS: The relative abundance of secondary BAs was decreased while the relative abundance of primary BAs was increased in irradiated mice, and LCA was the most obvious change. BAmix and LCA alleviated irradiation-induced intestinal injury in a mouse model, as reflected by reduced body weight loss, longer colon, higher villus, more crypts, and increased Lgr5 expression. In intestinal organoids, BAmix and LCA enhanced newborn crypts formation after irradiation. LCA treatment improved the expression of TGR5 and YAP1 in mouse intestinal crypts. LCA has potential to reduce the inflammation levels in irradiated mice. Additionally, the expression levels of TGR5 and YAP1 in the colonic mucosa of patients with radiation enteritis were also significantly decreased. CONCLUSIONS: Radiation-induced intestinal injury is associated with disorders of BAs metabolism, and treatment with LCA had a protective effect against radiation-induced intestinal injury in mice by modulating TGR5 and YAP1.
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Traumatismos por Radiación , Ratones , Animales , Traumatismos por Radiación/patología , Colon , Mucosa Intestinal/patología , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/farmacología , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.
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Humanos , Enfermedad de Castleman/patología , Células Plasmáticas/patología , Enfermedad Relacionada con Inmunoglobulina G4 , China , Linfadenopatía/patología , Inflamación/patología , Ganglios Linfáticos/patología , Diagnóstico Diferencial , Linfadenitis/patología , Inmunoglobulina G/metabolismoRESUMEN
High tumor mutation load (TMB-H, or TMB ≥ 10) has been approved by the U.S. FDA as a biomarker for pembrolizumab treatment of solid tumors, including nonsmall cell lung cancer (NSCLC). Patients with cancer who have immunotherapy-resistant gene mutations cannot achieve clinical benefits even in TMB-H. In this study, we aimed to identify gene mutations associated with immunotherapy resistance and further informed mechanisms in NSCLC. A combined cohort of 350 immune checkpoint blockade-treated patients from Memorial Sloan Kettering Cancer Center (MSKCC) was used to identify genes whose mutations could negatively influence immunotherapy efficacy. An external NSCLC cohort for which profession-free survival (PFS) data were available was used for independent validation. CIBERSORT algorithms were used to characterize tumor immune infiltrating patterns. Immunogenomic features were analysed in the TCGA NSCLC cohort. We observed that PBRM1 mutations independently and negatively influence immunotherapy efficacy. Survival analysis showed that the overall survival (OS) and PFS of patients with PBRM1 mutations (MT) were significantly shorter than the wild type (WT). Moreover, compared with PBRM1-WT/TMB-H group, OS was worse in the PBRM1-MT/TMB-H group. Notably, in patients with TMB-H/PBRM1-MT, it was equal to that in the low-TMB group. The CIBERSORT algorithm further confirmed that the immune infiltration abundance of CD8+ T cells and activated CD4+ memory T was significantly lower in the MT group. Immunogenomic differences were observed in terms of immune signatures, T-cell receptor repertoire, and immune-related genes between WT and MT groups. Nevertheless, we noticed an inverse relationship, given that MT tumors had a higher TMB than the WT group in MSKCC and TCGA cohort. In conclusion, our study revealed that NSCLC with PBRM1 mutation might be an immunologically cold phenotype and exhibited immunotherapy resistance. NSCLC with PBRM1 mutation might be misclassified as immunoresponsive based on TMB.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Fenotipo , Inmunoterapia , Mutación , Factores Inmunológicos , Proteínas de Unión al ADN , Factores de Transcripción/genéticaRESUMEN
Purpose: Hypoxia has crucial functions in the development and metastasis of cervical cancer by inducing the expression of numerous genes, including microRNA genes. But we know little about how the hypoxia factors and microRNAs orchestrate to regulate hallmarks of cervical cancer cells. Methods: We conducted RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) experiments to investigate the targets of HIF-3α or miR-630. ChIP-qPCR and RT-qPCR were carried out to validate the results of ChIP-seq and RNA-seq. Cellular, molecular, and radiation experiments were conducted to explore the functions of miR-630. Results: In this study, we showed that hypoxia-induced overexpression of HIF-3α increased the expression of dozens of miRNAs, including miR-630. Hypoxia could also directly induce miR-630 expression. ChIP-seq data showed that HIF-3α activates miR-630 expression by directly binding to the promoter of its host gene. Meanwhile, stable overexpression of miR-630 increased the expression of HIF-3α, but repressed the expression of HIF-1α, indicating a positive feedback loop between HIF-3α and miR-630. Consequently, stable overexpression of miR-630 in HeLa cells promotes cancer hallmarks, including radioresistance, inhibition of apoptosis, increased migration and invasion, and EMT-mediated metastasis. Meanwhile, inhibition of miR-630 showed opposite features. Conclusion: Taken together, our findings indicate a novel hypoxia-induced HIF-3α and miR-630 regulatory feedback loop contributing to metastasis and progression of cervical cancer cells and suggest that HIF-3α and miR-630 might act as potential biomarkers and therapeutic targets for cervical cancer in the future.
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Proteínas Reguladoras de la Apoptosis , MicroARNs , Neoplasias del Cuello Uterino , Femenino , Humanos , Células HeLa , Hipoxia/genética , MicroARNs/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Proteínas Reguladoras de la Apoptosis/genética , Retroalimentación FisiológicaRESUMEN
The study aimed to elucidate abscopal effects of thoracic X-ray irradiation on spermatogenesis in mice. Male C57BL/6 mice were randomly divided into sham group and radiation group, and subjected to thorax fractionated X-ray irradiation or sham irradiation with the total dose of 5 Gy/day for each animal for four consecutive days. After irradiation, sperm morphology was observed, and sperm number was counted under microscope, and sperm apoptosis was detected by flow cytometry. Meanwhile, testis index was calculated, testicular morphology was observed using haematoxylin-eosin (HE) staining, and testicular ultrastructure was observed under transmission electron microscopy. The permeability of blood-testis barrier (BTB) was detected by Evans Blue fluorescence colorimetry. The protein levels of Bcl-2 associated X protein (Bax), B-cell leukemia-lymphoma-2 (Bcl-2) and Cleaved caspase 3, promyelocytic leukaemia zinc finger (PLZF) and c-kit proto-oncogene (c-kit) in testes were determined by western blotting (WB). The location of apoptotic cells was confirmed by terminal deoxynucleotidyl transferase (TdT) enzymaticated dUTP nick end labelling (TUNEL) assay. The levels of tumor necrosis factor alpha (TNF-α), transforming growth factor-ß1 (TGF-ß1), interleukin 10 (IL-10) were measured by enzyme-linked immunosorbent assay (ELISA). The levels of Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by the biochemical assay kit. Compared with sham group, the sperm quality of mice in radiation group showed decreased number and survival rate, along with increased abnormality and total apoptosis rate. The testis index of irradiated mice was lower, the testicular apoptosis was increased, and their testicular histology and ultrastructure was severely damaged. The permeability of BTB was increased, the level of PLZF in testis was decreased, and the level of c-kit was increased by irradiation. After irradiation, the levels of TNF-α, TGF-ß1, IL-10, T-SOD and MDA in testes were significantly changed. Taken together, abscopal effects of thoracic X-ray irradiation on spermatogenesis were obvious, which could decrease sperm quality and damage testicular morphology and increase the permeability of BTB, and a series of inflammation and oxidative stress factors were involved in the process. These findings provide novel insights into prevention and treatment for male reproductive damage induced by clinical thoracic irradiation.
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The high temperature of formation and multiple stages of leakage zone seriously affect the efficiency and safety of drilling and cementing operations. To improve leakage plugging quality before the cementing process, the hydrophobic associating polymer PHAAO was synthesized from acrylamide (AM), 2-acrylamide-2-methyl propane sulfonic acid (AMPS), and the long side-chain hydrophobic monomer octadecyl dimethyl allyl ammonium chloride (ODAAC) in this study. The structure and molecular weight of the polymer were characterized, and it was proved that the polymer has strong association properties and excellent heat resistance. Utilizing the bridge plugging principle, the polymer PHAAO was used with 36-mesh walnut shells and lignin fiber to form a compound plugging agent. This agent was added to spacer fluid to become a plugging spacer. API water loss tests and loading capacity tests under high temperatures show that the filter cake formed by the spacer fluid is dense. The sealing pressure of the spacer fluid on a 1 mm crack can reach 6.5 MPa at 160 °C, and it has good compatibility with cement slurry. A scanning electron microscopy (SEM) test was conducted to explore the membrane formation mechanism of the polymer. An ultra-low permeability membrane is formed on the surface of the filter cake from the spacer fluid due to the hydrophobic association and hydrogen bonding between the polymer and lignin fiber, thereby greatly reducing the loss of spacer fluid.
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Human papillomavirus (HPV) is the most common risk factor for the occurrence of cervical cancer (CC). In recent years, the important roles of long noncoding RNAs (lncRNAs) in CC have emerged, but studies on the relationship between lncRNAs and HPVpositive (HPV+) CC remain scarce. The present study aimed to investigate whether lncRNA deleted in lymphocytic leukemia 1 (DLEU1) is associated with HPV infection and explore the clinical significance of DLEU1 in HPV+ patients with CC. DLEU1 expression was detected by reverse transcriptionquantitative PCR. The ability of DLEU1 to screen patients with CC from controls and differentiate individuals with different HPV infection status was evaluated by receiver operating characteristic analysis. The association of DLEU1 with the survival prognosis of patients with CC was assessed by KaplanMeier survival analysis and Cox regression analysis. The RNA Interactome Database was used to predict molecules interacting with DLEU1. The results indicated that DLEU1 expression was significantly upregulated in CC tissues and cell lines, particularly in those that were HPV+. In addition, DLEU1 had a high diagnostic value in discriminating patients with CC and differentiating between HPV+ and HPV patients with CC, and had a certain ability to screen HPV+ controls. DLEU1 was correlated with HPV infection in CC patients. Furthermore, DLEU1 was indicated to be associated with survival prognosis in both total patients with CC and HPV+ patients with CC, and independently predict the prognosis of patients with CC. Most of the molecules interacting with DLEU1 were microRNAs. In conclusion, abnormal DLEU1 expression is associated with HPV infection and may serve as a diagnostic and prognostic biomarker for HPV+ patients with CC.