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1.
PLoS One ; 19(6): e0305190, 2024.
Article in English | MEDLINE | ID: mdl-38857240

ABSTRACT

This study aimed to explore the application effects of cluster process control and routine nursing on the prevention of pressure injury (PI) in patients undergoing head and neck cancer surgery and to provide a basis for reducing the occurrence of PI, thereby promoting the safety of the patients. This was a retrospective study. Patients with head and neck cancers who underwent surgical treatment in the Department of Otolaryngology at the Second Affiliated Hospital of Fujian Medical University from July 2022 to June 2023 were selected as the research participants. Participants were classified into experimental and control groups using a convenience sampling method. In the experimental group, cluster process control was implemented, while routine nursing management was applied in the control group. The incidence of PI (p = 0.028) and healing time (p = 0.035) in the experimental group were lower than those in the control group. The process management ability of nurses in the experimental group was significantly improved, with the results for the Braden scale (p = 0.023), effective decompression (p = 0.002), floating heel (p = 0.002), nutrition monitoring (p = 0.005), and patient satisfaction in the experimental group being higher than those in the control group (p = 0.007). This study effectively demonstrated the effect of cluster process control in reducing the incidence of PI in patients undergoing head and neck cancer surgery, thereby determining that cluster process control is suitable for clinical application.


Subject(s)
Head and Neck Neoplasms , Pressure Ulcer , Humans , Head and Neck Neoplasms/surgery , Female , Male , Middle Aged , Retrospective Studies , Pressure Ulcer/prevention & control , Aged , Adult , Incidence
2.
Int J Genomics ; 2024: 7263358, 2024.
Article in English | MEDLINE | ID: mdl-38938448

ABSTRACT

Background: In the context of hepatocellular carcinoma (HCC), tumor-associated macrophages (TAMs) are pivotal for the immunosuppressive nature of the tumor microenvironment (TME). This investigation delves into the functional transformations of TAMs within the TME by leveraging single-cell transcriptomics to pinpoint critical genes influencing TAM subset polarization. Methods: We procured single-cell and bulk transcriptomic data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), implementing quality assurance, dimensional reduction, clustering, and annotation on the single-cell sequencing data. To examine cellular interactions, CellChat was utilized, while single-cell regulatory network inference and clustering (SCENIC) was applied to deduce transcription factors (TFs) and their associated targets. Through gene enrichment, survival, and immune infiltration correlation analyses, we sought to pinpoint and validate influential genes. A TAM model under HCC conditions was then established to confirm the expression levels of these key genes. Results: Our analysis encompassed 74,742 cells and 23,110 genes. Through postdimensional reduction and clustering, we identified seven distinct cell types and nine TAM subtypes. Analysis via CellChat highlighted a predominance of M2-phenotype-inclined TAM subsets within the tumor's core. SCENIC pinpointed the transcription factor PRDM1 and its target genes as pivotal in this region. Further analysis indicated these genes' involvement in macrophage polarization. Employing trajectory analysis, survival analysis, and immune infiltration correlation, we scrutinized and validated genes likely directing M2 polarization. Experimental validation confirmed PRDM1's heightened expression in TAMs conditioned by HCC. Conclusions: Our findings suggest the PRDM1 gene is a key regulator of M2 macrophage polarization, contributing to the immunosuppressive TME in HCC.

3.
STAR Protoc ; 5(2): 103042, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38850537

ABSTRACT

The mitochondrial stress test is a gold-standard approach for assessing adipose tissue physiological functions and pathological changes. Here, we present a protocol for conducting Seahorse assays using ex vivo mouse brown and white adipose depots. We describe steps for rehydrating the cartridge, preparing freshly harvested fat depots, placing them onto an islet capture plate, and incubating them in a non-CO2 incubator. We then detail procedures for adding mitochondrial stressor solutions and conducting the mitochondrial stress test using the Seahorse XFe24 Analyzer. For complete details on the use and execution of this protocol, please refer to An et al.1.


Subject(s)
Adipose Tissue, Brown , Adipose Tissue, White , Mitochondria , Animals , Mice , Adipose Tissue, White/metabolism , Adipose Tissue, Brown/metabolism , Mitochondria/metabolism
4.
PLoS Negl Trop Dis ; 18(5): e0012182, 2024 May.
Article in English | MEDLINE | ID: mdl-38820544

ABSTRACT

OBJECTIVE: To understand the epidemiological distribution characteristics of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in Yangquan City, Shanxi Province, China, from 2006 to 2021, to explore the influencing factors leading to the re-emergence of the epidemic, and to provide a basis for the formulation of targeted control strategies. METHODS: Case information spanning from 2006 to 2021 in Yangquan City was collected for a retrospective case-control study conducted from June to September 2022. A 1:3 matched ratio was employed. A questionnaire was utilized to gather data on basic information, demographic characteristics, awareness of MT-ZVL knowledge, residence, and dog breeding and living habits. The study employed a multifactorial conditional stepwise logistic regression model to analyze the influencing factors. RESULTS: A total of 508 subjects was analyzed. Risk factors for MT-ZVL included the use of soil/stone/concrete as building materials (OR = 3.932), presence of nearby empty/stone stack houses (OR = 2.515), dog breeding (OR = 4.215), presence of stray dogs (OR = 2.767), and neighbor's dog breeding (OR = 1.953). Protective factors comprised knowledge of MT-ZVL (OR = 0.113) and using mosquito repellents (OR = 0.388). The findings indicate significant associations between environmental and behavioral factors and MT-ZVL incidence in Yangquan City, Shanxi Province, China, from 2006 to 2021. These results underscore the importance of public awareness campaigns and targeted interventions aimed at reducing exposure to risk factors and promoting protective measures to mitigate the re-emergence of MT-ZVL outbreaks. CONCLUSION: House building materials, presence of neighboring empty houses, breeding domestic dogs and distribution of stray dogs surrounding the home are risk factors for MT-ZVL. Awareness of MT-ZVL and implementation of preventive measures during outdoor activities in summer and autumn are protective and may reduce the risk of MT-ZVL.


Subject(s)
Leishmaniasis, Visceral , Zoonoses , Animals , China/epidemiology , Humans , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/transmission , Leishmaniasis, Visceral/prevention & control , Zoonoses/epidemiology , Zoonoses/transmission , Female , Dogs , Male , Adult , Risk Factors , Middle Aged , Retrospective Studies , Case-Control Studies , Young Adult , Adolescent , Dog Diseases/epidemiology , Dog Diseases/parasitology , Dog Diseases/transmission , Child , Surveys and Questionnaires , Aged , Child, Preschool , Health Knowledge, Attitudes, Practice
5.
Gut ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724220

ABSTRACT

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

6.
Mar Pollut Bull ; 202: 116378, 2024 May.
Article in English | MEDLINE | ID: mdl-38678731

ABSTRACT

Based on the monitoring data of 137Cs and 90Sr in Tian Bay in 2005-2023, the impacts of the operation of Tianwan Nuclear Power Plant on the marine ecosystem were assessed. The 137Cs and 90Sr activity concentrations in the seawater and sediment varied within the background ranges. The radiation dose rates derived from 137Cs and 90Sr for the marine organisms ranged from 2.4 × 10-5 to 2.2 × 10-4 nGy/h, it was far below the most conservative screening dose rate (10 µGy/h). The committed effective dose for humans was 0.070-0.094 µSv, 1/1500th of the world's mean annual effective dose (0.12 mSv) from ingesting food containing uranium and thorium series nuclides. Radiation risk assessment showed no radiation risk for the long-term discharge of nuclear wastes in the future. Overall, the long-term normal operation of TNPPs has almost no radiation impact on the adjacent marine ecosystem.


Subject(s)
Aquatic Organisms , Cesium Radioisotopes , Ecosystem , Nuclear Power Plants , Radiation Monitoring , Seawater , Water Pollutants, Radioactive , Water Pollutants, Radioactive/analysis , Cesium Radioisotopes/analysis , Seawater/chemistry , China , Geologic Sediments/chemistry , Risk Assessment
7.
Mar Pollut Bull ; 202: 116301, 2024 May.
Article in English | MEDLINE | ID: mdl-38608429

ABSTRACT

This study established specialized radiation dose models to evaluate the internal radiation doses derived from 137Cs and 134Cs in fishes in the port of the Fukushima Daiichi Nuclear Power Plant from 2012 to 2023. By August 2018, the activities of 134Cs and 137Cs in fishes decreased at the T1/2 of 176 d and 191 d, respectively. The corresponding mass concentrations were far lower than 1 mg/kg and the chemical toxicity can be negligible. Regarding radiotoxicity, 18,000 Bq/kgfresh weight of 134Cs and 137Cs in grouper Sebastes schlegelii produced 276 µGy/h of radiation dose, which was below the no-effect-dose-rate benchmarks (400 µGy/h). 740,000 Bq/kgfresh weight of 134Cs and 137Cs in greenling Hexagrammos otakii produced 12,600 µGy/h of radiation dose, which was much higher than 400 µGy/h, indicating the possibility of radiation effects. If a person eats these two reported fishes, the resulting committed effective doses for humans are 7.7 µSv and 6.31 mSv, respectively.


Subject(s)
Cesium Radioisotopes , Fishes , Fukushima Nuclear Accident , Nuclear Power Plants , Radiation Monitoring , Water Pollutants, Radioactive , Animals , Cesium Radioisotopes/analysis , Water Pollutants, Radioactive/analysis , Japan , Radiation Dosage
8.
Sci Rep ; 13(1): 19616, 2023 11 10.
Article in English | MEDLINE | ID: mdl-37949927

ABSTRACT

The vibration controlled transient elastography (VCTE) technique was used to assess the effectiveness of a Biejia Decoction pill in combination with Entecavir in the treatment of hepatitis B liver fibrosis/cirrhosis. We randomly selected 120 patients to receive entecavir and 119 patients to receive both entecavir and Biejia Decoction Pill, which both with hepatitis B liver fibrosis/cirrhosis visited the Second Affiliated Hospital of Nanchang University between January 2019 and February 2022. The observation group got ETV (entecavir) and Biejia Decoction pills, whereas the control group received only standard ETV antiviral medication. Based on the grading of the VCTE detection value (LSM) initially diagnosed for patients with hepatitis B liver fibrosis/cirrhosis, we divided the patients into two subgroups of liver fibrosis and cirrhosis. In addition, patients with liver fibrosis were divided into mild and moderate subgroups according to their VCTE values. Patients were measured for liver hardness after three, six, nine, and twelve months of treatment with VCTE. Biejia Decoction Pill combined with ETV on HBV liver fibrosis/cirrhosis was evaluated by comparing patients' changes in liver hardness and HBV-DNA negative conversion rates before and after treatment in each group at the same baseline. The LSM (liver elasticity value) of the observation group and the control group after treatment was lower than that before treatment, and the difference was statistically significant (P < 0.0001); The LSM of the observation group after treatment was significantly lower than that of the control group, and the difference was also statistically significant (P = 0.0005 < 0.05). In the subgroup of liver fibrosis, the number of patients with moderate and severe liver fibrosis who completely reversed liver fibrosis after treatment in the treatment group was far more than that in the control group, and the difference between the two groups was statistically significant (χ2 = 4.82 P = 0.028 < 0.05) 。 When the treatment course was more than 9 months, the negative conversion rate of patients in the observation group reached 87.4%, which was higher than that in the control group (70.8%), and the difference was statistically significant (P = 0.002 < 0.05); After 12 months of treatment, the negative conversion rate of patients in the observation group was as high as 95%, which was significantly higher than 76.67% in the control group (P < 0.001). The degree of liver fibrosis was significantly improved when Biejia Decoction Pill was combined with ETV in patients with liver fibrosis/cirrhosis due to hepatitis B. The virological response rate to HBV-DNA increased with the prolongation of treatment, and the Biejia Decoction Pill assists with entecavir in antiviral therapy.


Subject(s)
Elasticity Imaging Techniques , Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/diagnosis , DNA, Viral , Vibration , Treatment Outcome , Hepatitis B/complications , Hepatitis B/drug therapy , Hepatitis B/chemically induced , Liver Cirrhosis/diagnosis , Antiviral Agents/therapeutic use , Hepatitis B virus/genetics
9.
Endocrinol Metab (Seoul) ; 38(5): 493-503, 2023 10.
Article in English | MEDLINE | ID: mdl-37816498

ABSTRACT

The growing recognition of mitochondria's crucial role in the regulation of white adipose tissue remodeling and energy balance underscores its significance. The marked metabolic diversity of mitochondria provides the molecular and cellular foundation for enabling adipose tissue plasticity in response to various metabolic cues. Effective control of mitochondrial function at the cellular level, not only in thermogenic brown and beige adipocytes but also in energy-storing white adipocytes, exerts a profound influence on adipose homeostasis. Furthermore, mitochondria play a pivotal role in intercellular communication within adipose tissue via production of metabolites with signaling properties. A more comprehensive understanding of mitochondrial regulation within white adipocytes will empower the development of targeted and efficacious strategies to enhance adipose function, leading to advancements in overall metabolic health.


Subject(s)
Adipocytes, White , Adipose Tissue , Humans , Adipocytes, White/metabolism , Adipose Tissue/metabolism , Signal Transduction , Mitochondria/metabolism , Thermogenesis , Obesity/metabolism
10.
Cell Death Dis ; 14(10): 670, 2023 10 11.
Article in English | MEDLINE | ID: mdl-37821439

ABSTRACT

Abnormal alternative splicing (AS) caused by alterations in spliceosomal factors is implicated in cancers. Standard models posit that splice site selection is mainly determined by early spliceosomal U1 and U2 snRNPs. Whether and how other mid/late-acting spliceosome components such as USP39 modulate tumorigenic splice site choice remains largely elusive. We observed that hepatocyte-specific overexpression of USP39 promoted hepatocarcinogenesis and potently regulated splice site selection in transgenic mice. In human liver cancer cells, USP39 promoted tumor proliferation in a spliceosome-dependent manner. USP39 depletion deregulated hundreds of AS events, including the oncogenic splice-switching of KANK2. Mechanistically, we developed a novel RBP-motif enrichment analysis and found that USP39 modulated exon inclusion/exclusion by interacting with SRSF6/HNRNPC in both humans and mice. Our data represented a paradigm for the control of splice site selection by mid/late-acting spliceosome proteins and their interacting RBPs. USP39 and possibly other mid/late-acting spliceosome proteins may represent potential prognostic biomarkers and targets for cancer therapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Mice , Animals , Alternative Splicing/genetics , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , RNA Splicing , Carcinogenesis/genetics , Serine-Arginine Splicing Factors/metabolism , Phosphoproteins/metabolism , Heterogeneous-Nuclear Ribonucleoprotein Group C/metabolism , Ubiquitin-Specific Proteases/metabolism
11.
Int J Mol Sci ; 24(19)2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37834325

ABSTRACT

Neuroblastoma (NB) is the most common extracranial solid tumor that affects developing nerve cells in the fetus, infants, and children. miR-124 is a microRNA (miRNA) enriched in neuronal tissues, and VAMP3 (vesicle-associated membrane protein 3) has been reported to be an miR-124 target, although the relationship between NB and miR-124 or VAMP3 is unknown. Our current work identified that miR-124 levels are high in NB cases and that elevated miR-124 correlates with worse NB outcomes. Conversely, depressed VAMP3 correlates with worse NB outcomes. To investigate the mechanisms by which miR-124 and VAMP3 regulate NB, we altered miR-124 or VAMP3 expression in human NB cells and observed that increased miR-124 and reduced VAMP3 stimulated cell proliferation and suppressed apoptosis, while increased VAMP3 had the opposite effects. Genome-wide mRNA expression analyses identified gene and pathway changes which might explain the NB cell phenotypes. Together, our studies suggest that miR-124 and VAMP3 could be potential new markers of NB and targets of NB treatments.


Subject(s)
MicroRNAs , Neural Stem Cells , Neuroblastoma , Child , Infant , Humans , Vesicle-Associated Membrane Protein 3/genetics , Vesicle-Associated Membrane Protein 3/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Phenotype , Neuroblastoma/metabolism , Neural Stem Cells/metabolism , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Cell Line, Tumor
12.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(9): 1127-1132, 2023 Sep 15.
Article in Chinese | MEDLINE | ID: mdl-37718426

ABSTRACT

Objective: To investigate the influence of buried thread nasal augmentation on dorsal soft tissue of nose and revision rhinoplasty. Methods: A clinical data of 29 patients requesting revision rhinoplasty after buried thread nasal augmentation, who were admitted between July 2017 and July 2019 and met the selection criteria, was retrospectively analyzed. All patients were female with an average age of 26.8 years (range, 18-43 years). The patiens were admitted to the hospital at 3-48 months after buried thread nasal augmentation (median, 15 months). Among them, there were 18 cases of insufficient nasal tip projection, 22 cases of insufficient nasal root projection, 7 cases of threads ectasia, 5 cases of threads exposure, 3 cases of infection, and 10 cases with two or more conditions. There were 9 cases of combined short nose deformity, 1 case of spherical hypertrophy of the nasal tip, 3 cases of deviation of the nasal columella, 3 cases of excessive width of the nasal base, and 1 case of nasal hump. Three infected patients only underwent threads removal and debridement. The rest patients underwent revision rhinoplasty, and the dorsum of the nose was made with polytetrafluoroethylene expansion; the tip of the nose was reshaped by taking autologous rib cartilage and alar cartilage in 16 cases, and by taking autologous septal cartilage and alar cartilage in another 10 cases. The threads and surrounding tissue specimens removed during operation were subjected to histologic observation. Nasal length and nasal tip projection were measured after revision rhinoplasty and the ratio was calculated to evaluate the nasal morphology; patient satisfaction was evaluated using the Likert 5-grade scale. Results: Patients were followed up 12-48 months (mean, 18 months). Inflammation was controlled in 3 patients with infections caused by buried thread nasal augmentation. The remaining 26 patients had satisfactory results immediately after revision rhinoplasty. Before revision rhinoplasty and at 7 days and 6 months after revision rhinoplasty, the nasal length was (4.11±0.34), (4.36±0.25), and (4.33±0.22) cm, respectively; the nasal tip projection was (2.34±0.25), (2.81±0.18), and (2.76±0.15) cm, respectively; and the nasal tip projection/nasal length ratio was 0.57±0.08, 0.65±0.05, and 0.64±0.04, respectively. There were significant differences in the nasal length and the nasal tip projection between time points ( P<0.05). There was a significant difference in the nasal tip projection/nasal length ratio between pre- and post-operation ( P<0.05), but there was no significant difference between 7 days and 6 months after operation ( P>0.05). The Likert score for satisfaction ranged from 1.5 to 5.0 (mean, 4.05). During follow-up period of 26 patients, no nasal prosthesis was exposed, and the shape of the nose was stable, and the nasal skin of 5 patients with exposed threads could be seen with different degrees of scarring; there was no infection, cartilage resorption, and no cartilage deformation, displacement, or exposure. Histological observation showed that absorbable threads were not only absorbed after implantation, but also with the prolongation of time, the inflammatory changes in the surrounding tissues caused by decomposition and absorption of the threads showed a gradual aggravation of the first, the heaviest inflammatory reaction in 6 to 12 months, and then gradually reduce the trend. Conclusion: After implantation of the absorbable thread into the subcutaneous tissue of the nasal dorsum, the nature of the thread is different from the body's own tissue, which will affect the soft tissue compliance of the nasal dorsum. The degradation and absorption of the thread will stimulate the infiltration of inflammatory cells and the proliferation of fibroblasts in the surrounding tissue and then form scar tissue, which will affect the design and effect of revision rhinoplasty.


Subject(s)
Rhinoplasty , Humans , Female , Adult , Male , Retrospective Studies , Reoperation , Nasal Cartilages , Nasal Septum , Cicatrix
13.
Front Endocrinol (Lausanne) ; 14: 1151757, 2023.
Article in English | MEDLINE | ID: mdl-37600696

ABSTRACT

Background: Thyroid eye disease (TED) is the most frequent orbital disease in adults and is characterized by the accumulation of orbital adipose tissue (OAT). It can lead to eyelid retraction or even vision loss. Orbital decompression surgery serves as the primary treatment for inactive TED by removing the excess OAT. However, there is a lack of alternative treatments to surgery due to the unclear understanding of the pathogenesis, particularly the metabolic features. Accordingly, our study was implemented to explore the content and features of metabolites of OATs from TED patients. Method: The OATs used in the current study were obtained from the orbital decompression surgery of seven patients with inactive TED. We also collected control OATs from eye surgical samples of five individuals with no history of autoimmune thyroid diseases, TED, or under non-inflammatory conditions. The liquid chromatography mass spectrometer was used for the measurements of the targeted metabolites. Afterwards, we performed differential metabolite assay analysis and related pathway enrichment analysis. Results: In our study, a total of 149 metabolite profiles were detected in all participants. There were significant differences in several metabolite profiles between the TED group and the control group, mainly including uric acid, oxidized glutathione, taurine, dGMP, oxidized glutathione 2, uracil, hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, and uridine 5'-monophosphate (all p-value < 0.05). The TED-related pathways identified included purine metabolism, beta-alanine metabolism, glutathione metabolism (p-values < 0.05). Our study found overlaps and differences including uric acid and uracil, which are in accordance with metabolites found in blood of patients with TED from previous study and several newly discovered metabolite by our study such as hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, compared to those tested from blood, OAT, or urine samples reported in previous studies. Conclusion: The findings of our study shed light on the metabolic features of OAT in individuals with TED. These results may help identify new treatment targets for TED, providing potential avenues for developing alternative treatments beyond ophthalmic surgery.


Subject(s)
Graves Ophthalmopathy , Adult , Humans , Graves Ophthalmopathy/surgery , Glutathione Disulfide , Uric Acid , Adipose Tissue , Biological Assay
14.
Cell Death Dis ; 14(6): 381, 2023 06 28.
Article in English | MEDLINE | ID: mdl-37380646

ABSTRACT

Cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in many types of cancer, including hepatocellular carcinoma (HCC). Epigenetic reprogramming of CSCs has emerged as a promising strategy for inducing the transition from malignancy to benignity. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is required for DNA methylation inheritance. Here, we investigated the role and mechanism of UHRF1 in regulating CSC properties and evaluated the impact of UHRF1 targeting on HCC. Hepatocyte-specific Uhrf1 knockout (Uhrf1HKO) strongly suppressed tumor initiation and CSC self-renewal in both diethylnitrosamine (DEN)/CCl4-induced and Myc-transgenic HCC mouse models. Ablation of UHRF1 in human HCC cell lines yielded consistent phenotypes. Integrated RNA-seq and whole genome bisulfite sequencing revealed widespread hypomethylation induced by UHRF1 silencing epigenetically reprogrammed cancer cells toward differentiation and tumor suppression. Mechanistically, UHRF1 deficiency upregulated CEBPA and subsequently inhibited GLI1 and Hedgehog signaling. Administration of hinokitiol, a potential UHRF1 inhibitor, significantly reduced tumor growth and CSC phenotypes in mice with Myc-driven HCC. Of pathophysiological significance, the expression levels of UHRF1, GLI1, and key axis proteins consistently increased in the livers of mice and patients with HCC. These findings highlight the regulatory mechanism of UHRF1 in liver CSCs and have important implications for the development of therapeutic strategies for HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Hedgehog Proteins , Carcinoma, Hepatocellular/genetics , Zinc Finger Protein GLI1 , Liver Neoplasms/genetics , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Neoplastic Stem Cells , CCAAT-Enhancer-Binding Proteins/genetics , Ubiquitin-Protein Ligases/genetics
15.
Chemosphere ; 336: 139314, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37354957

ABSTRACT

The Fukushima Daiichi Nuclear Power Plant (FDNPP) has generated quantities of polluted water since the accident in 2011 triggered by the massive earthquake. In order to understand the FDNPP accident comprehensively and to provide a basic reference for predicting the transport of the treated nuclear contaminated water in the Northwest Pacific further, the distributions of 137Cs and 134Cs in the seawater as deep as 2000 m were determined in the subtropical region in May 2013. The results suggested that the radiocesium from FDNPP still existed in May 2013. But no FDNPP-derived radiocesium was found below 1000 m layer. The FDNPP accident contributed 0.46 PBq of 137Cs to the upper 500 m of water column, which was ∼1.6 times of the background amount of 137Cs (0.28 PBq). The maximum activities of 137Cs and 134Cs were 7.88 Bq/m3 and 3.40 Bq/m3, respectively. It is mainly because of the Subtropical Mode Water (STMW) that carried 137Cs and 134Cs to the subtropical region along the subsurface isopycnals (25.0-25.6 δθ). As time went on, more FDNPP-derived radiocesiums were transported to the subtropical region and to the subsurface layer by the STMW than ever. The cyclonic mesoscale eddy further promoted more radiocesiums downward transport and deeper penetration on the basis of the subduction of STMW. However, the formation of the vertical stratification and the presence of the low salinity water mass (at the depth of ∼500-∼700 m) restrained the penetration of the radiocesium into deeper and interior ocean and thus the FDNPP-derived 137Cs and 134Cs in the subtropical area mainly distributed in the upper 500 m layer.


Subject(s)
Fukushima Nuclear Accident , Radiation Monitoring , Water Pollutants, Radioactive , Pacific Ocean , Water Pollutants, Radioactive/analysis , Radiation Monitoring/methods , Seawater , Cesium Radioisotopes/analysis , Water , Japan
16.
Int J Nanomedicine ; 18: 3035-3046, 2023.
Article in English | MEDLINE | ID: mdl-37312935

ABSTRACT

Angiogenesis is an essential mechanism for the progression of gynecological cancers. Although approved anti-angiogenic drugs have demonstrated clinical efficacy in treating gynecological cancers, the full potential of therapeutic strategies based on tumor blood vessels has not yet been realized. This review summarizes the latest angiogenesis mechanisms involved in the progression of gynecological cancers and discusses the current clinical practice of approved anti-angiogenic drugs and related clinical trials. Given the close relationship between gynecological cancers and blood vessels, we highlight more delicate strategies for regulating tumor vessels, including wise drug combinations and smart nano-delivery platforms to achieve highly efficient drug delivery and overall vessel microenvironment regulation. We also address current challenges and future opportunities in this field. We aim to generate interest in therapeutic strategies that target blood vessels as a key entry point and offer new potential and inspiration for combating gynecological cancers.


Subject(s)
Angiogenesis Inhibitors , Neoplasms , Humans , Drug Delivery Systems , Tumor Microenvironment
17.
Small Methods ; 7(6): e2201659, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37093170

ABSTRACT

The exploration of cost-effective multifunctional electrodes with high activity toward energy storage and conversion systems, such as self-powered alkaline water electrolysis, is very meaningful, although studies remain quite limited. Herein, a heterogeneous nickel-molybdenum (NiMo)-based electrode is fabricated for the first time as a trifunctional electrode for asymmetric supercapacitor (ASC), hydrogen evolution reaction, and oxygen evolution reaction. The trifunctional electrode consists of Ni4 Mo and MoO2 (denoted Ni4 Mo/MoO2 ) with hierarchical nanorod heterostructure and abundant heterogeneous nanointerfaces creating sufficient active sites and efficient charge transfer for achieving high performance self-power electrochemical devices. The ASC consists of the as-prepared Ni4 Mo/MoO2 positive electrode, showing a broad potential window of 1.6 V, and a maximum energy density of 115.6 Wh kg-1 , while the alkaline overall water splitting (OWS) assembled using the as-prepared Ni4 Mo/MoO2 as bifunctional catalysts only requires a low cell voltage of 1.48 V to achieve a current density of 10 mA cm-2 in aqueous alkaline electrolyte. Finally, by integrating the Ni4 Mo/MoO2 -based ASC and OWS devices, an aqueous self-powered OWS is assembled, which self-power the OWS to generate hydrogen gas and oxygen gas, verifying great potential of the as-prepared Ni4 Mo/MoO2 for sustainable and renewable energy storage and conversion system.

18.
Cell Rep ; 42(1): 111984, 2023 01 31.
Article in English | MEDLINE | ID: mdl-36640347

ABSTRACT

Lysosomal amino acid accumulation is implicated in several diseases, but its role in insulin resistance, the central mechanism to type 2 diabetes and many metabolic diseases, is unclear. In this study, we show the hepatic expression of lysosomal membrane protein solute carrier family 7 member 14 (SLC7A14) is increased in insulin-resistant mice. The promoting effect of SLC7A14 on insulin resistance is demonstrated by loss- and gain-of-function experiments. SLC7A14 is further demonstrated as a transporter resulting in the accumulation of lysosomal γ-aminobutyric acid (GABA), which induces insulin resistance via inhibiting mTOR complex 2 (mTORC2)'s activity. These results establish a causal link between lysosomal amino acids and insulin resistance and suggest that SLC7A14 inhibition may provide a therapeutic strategy in treating insulin resistance-related and GABA-related diseases and may provide insights into the upstream mechanisms for mTORC2, the master regulator in many important processes.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Mice , Animals , Diabetes Mellitus, Type 2/metabolism , Mechanistic Target of Rapamycin Complex 2/metabolism , Amino Acids/metabolism , gamma-Aminobutyric Acid/metabolism , Lysosomes/metabolism
19.
Article in English | MEDLINE | ID: mdl-36498370

ABSTRACT

Catalytic conversion of cellulose to liquid fuel and highly valuable platform chemicals remains a critical and challenging process. Here, bismuth-decorated ß zeolite catalysts (Bi/ß) were exploited for highly efficient hydrolysis and selective oxidation of cellulose to biomass-derived glycolic acid in an O2 atmosphere, which exhibited an exceptionally catalytic activity and high selectivity as well as excellent reusability. It was interestingly found that as high as 75.6% yield of glycolic acid over 2.3 wt% Bi/ß was achieved from cellulose at 180 °C for 16 h, which was superior to previously reported catalysts. Experimental results combined with characterization revealed that the synergetic effect between oxidation active sites from Bi species and surface acidity on H-ß together with appropriate total surface acidity significantly facilitated the chemoselectivity towards the production of glycolic acid in the direct, one-pot conversion of cellulose. This study will shed light on rationally designing Bi-based heterogeneous catalysts for sustainably generating glycolic acid from renewable biomass resources in the future.


Subject(s)
Cellulose , Zeolites , Cellulose/chemistry , Zeolites/chemistry , Bismuth , Catalysis
20.
Front Oncol ; 12: 904633, 2022.
Article in English | MEDLINE | ID: mdl-36578923

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most malignant cancers worldwide, with high mortality. However, the molecular regulatory mechanisms of liver cancer, especially transcriptional and post-transcriptional mechanisms, should be further studied. Here we used chromatin and cross-linking immunoprecipitation with high throughput sequencing methods (ChIP-seq and CLIP-seq) to capture the global binding profiles on RNAs and DNAs of Enhancer of zeste homolog 2 (EZH2) and its partner Jumonji And AT-Rich Interaction Domain Containing 2 (JARID2) in liver carcinoma cell lines (HepG2) and normal liver cell line (THLE-2), respectively. We also integrated HCC transcriptome data from the TCGA to analyze the expression pattern of bound genes. We found that EZH2 and JARID2 both showed distinct binding profiles between HepG2 and THLE-2 cells. By binding to the primary RNAs, bound transcripts of EZH2 and JARID2 in HepG2 showed significantly increased transcriptional levels in HCC patients. By performing gene set enrichment analysis (GSEA), the bound transcripts were also highly related to HCC development. We also found EZH2 and JARID2 could specifically bind to several long noncoding RNAs (lncRNAs), including H19. By exploring the DNA binding profile, we detected a dramatically repressed DNA binding ability of EZH2 in HepG2 cells. We also found that the EZH2-bound genes showed slightly increased transcriptional levels in HepG2 cells. Integrating analysis of the RNA and DNA binding profiles suggests EZH2 and JARID2 shift their binding ability from DNA to RNA in HepG2 cells to promote cancer development in HCC. Our study provided a comprehensive and distinct binding profile on RNAs and DNAs of EZH2 and JARID2 in liver cancer cell lines, suggesting their potential novel functional manners to promote HCC development.

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