Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 178
Filter
1.
ERJ Open Res ; 10(4)2024 Jul.
Article in English | MEDLINE | ID: mdl-38957167

ABSTRACT

Background: Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5 and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults. Methods: We calculated the mean 722-day personal exposure estimates of PM1, PM2.5 and PM10 at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10 concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months. Results: We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5 and PM10 was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02-1.45); PM2.5: 1.24 (1.04-1.48); PM10: 1.30 (1.07-1.57)), wheeze (PM1: 1.27 (1.11-1.44); PM2.5: 1.30 (1.14-1.48); PM10: 1.34 (1.17-1.55)), persistent cough (PM1: 1.33 (1.06-1.66); PM2.5: 1.36 (1.09-1.71); PM10: 1.31 (1.02-1.68)) and dyspnoea (PM1: 2.10 (1.84-2.41); PM2.5: 2.17 (1.90-2.48); PM10: 2.29 (1.96-2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5 and PM10 with asthma and asthma-related respiratory symptoms were slightly stronger in males. Conclusion: Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.

2.
PLoS One ; 19(6): e0303170, 2024.
Article in English | MEDLINE | ID: mdl-38857222

ABSTRACT

OBJECTIVE: The aim of this study is to investigate the potential causal relationship between autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and Type 1 diabetes, and age-related macular degeneration (AMD). By utilizing the two-sample Mendelian Randomization (MR) approach, we endeavor to address this complex medical issue. METHODS: Genome-wide association study (GWAS) data for autoimmune diseases and AMD were obtained from the IEU Open GWAS database and the FinnGen consortium. A series of stringent SNP filtering steps was applied to ensure the reliability of the genetic instruments. MR analyses were conducted using the TwoSampleMR and MR-PRESSO packages in R. The inverse-variance weighted (IVW) method served as the primary analysis, complemented by multiple supplementary analyses and sensitivity tests. RESULTS: Within the discovery sample, only a statistically significant inverse causal relationship between multiple sclerosis (MS) and AMD was observed (OR = 0.92, 95% CI: 0.88-0.97, P = 0.003). This finding was confirmed in the replication sample (OR = 0.85, 95% CI: 0.80-0.89, P = 3.32×10-12). No statistically significant associations were detected between systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Type 1 diabetes and AMD. CONCLUSION: Strong evidence is provided by this study to support the existence of an inverse causal relationship between multiple sclerosis and age-related macular degeneration. However, no causal evidence was found linking other autoimmune diseases with AMD. These findings not only offer novel insights into the potential etiological mechanisms underlying AMD but also suggest possible directions for future clinical interventions.


Subject(s)
Autoimmune Diseases , Genome-Wide Association Study , Macular Degeneration , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Humans , Macular Degeneration/genetics , Autoimmune Diseases/genetics , Autoimmune Diseases/epidemiology , Multiple Sclerosis/genetics , Arthritis, Rheumatoid/genetics , Male , Diabetes Mellitus, Type 1/genetics , Inflammatory Bowel Diseases/genetics , Female
3.
Food Chem ; 454: 139796, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38797102

ABSTRACT

This study aimed to present a selective and effective method for analyzing quinolones (QNs) in food matrix. Herein, a NiFe2O4-based magnetic sodium disulfonate covalent organic framework (NiFe2O4/COF) was prepared using a simple solvent-free grinding method, and was adopted as a selective adsorbent for magnetic solid phase extraction of QNs. Coupled with UHPLC-Q-Orbitrap HRMS, an efficient method for simultaneous detection of 18 kinds of QNs was established. The method exhibited good linearity (0.01-100 ng g-1), high sensitivity (LODs ranging from 0.0011 to 0.0652 ng g-1) and precision (RSDs below 9.5%). Successful extraction of QNs from liver and kidney samples was achieved with satisfactory recoveries ranging from 82.2% to 108.4%. The abundant sulfonate functional groups on NiFe2O4/COF facilitated strong affinity to QNs through electrostatic and hydrogen bonding interactions. The proposed method provides a new idea for the extraction of contaminants with target selectivity.


Subject(s)
Ferric Compounds , Food Contamination , Metal-Organic Frameworks , Quinolones , Solid Phase Extraction , Solid Phase Extraction/methods , Solid Phase Extraction/instrumentation , Quinolones/analysis , Quinolones/isolation & purification , Quinolones/chemistry , Chromatography, High Pressure Liquid , Food Contamination/analysis , Animals , Metal-Organic Frameworks/chemistry , Ferric Compounds/chemistry , Nickel/chemistry , Nickel/analysis , Nickel/isolation & purification , Mass Spectrometry , Adsorption , Liver/chemistry
4.
Environ Sci Technol ; 58(17): 7291-7301, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38623940

ABSTRACT

The environmental dissemination of extracellular antibiotic resistance genes (eARGs) in wastewater and natural water bodies has aroused growing ecological concerns. The coexisting chemical pollutants in water are known to markedly affect the eARGs transfer behaviors of the environmental microbial community, but the detailed interactions and specific impacts remain elusive so far. Here, we revealed a concentration-dependent impact of dimethyl phthalate (DMP) and several other types of phthalate esters (common water pollutants released from plastics) on the natural transformation of eARGs. The DMP exposure at an environmentally relevant concentration (10 µg/L) resulted in a 4.8-times raised transformation frequency of Acinetobacter baylyi but severely suppressed the transformation at a high concentration (1000 µg/L). The promotion by low-concentration DMP was attributed to multiple mechanisms, including increased bacterial mobility and membrane permeability to facilitate eARGs uptake and improved resistance of the DMP-bounded eARGs (via noncovalent interaction) to enzymatic degradation (with suppressed DNase activity). Similar promoting effects of DMP on the eARGs transformation were also found in real wastewater and biofilm systems. In contrast, higher-concentration DMP suppressed the eARGs transformation by disrupting the DNA structure. Our findings highlight a potentially underestimated eARGs spreading in aquatic environments due to the impacts of coexisting chemical pollutants and deepen our understanding of the risks of biological-chemical combined pollution in wastewater and environmental water bodies.


Subject(s)
Drug Resistance, Microbial , Phthalic Acids , Drug Resistance, Microbial/genetics , Wastewater , Biofilms/drug effects , Water Pollutants, Chemical/toxicity
5.
Anal Chim Acta ; 1294: 342293, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38336414

ABSTRACT

BACKGROUND: The practical application of moisture sensitive metal organic frameworks (MOFs) in extraction technology faces challenges related to competitive adsorption and water stability. The target analytes cannot be effectively extracted under humid conditions due to the competitive moisture adsorption and/or framework structure collapse of MOFs. In this study, the microporous organic networks (MONs) were synthesized through Sonogashira coupling reaction to use for hydrophobic modification on the surface of MOF-199. RESULTS: The MOF-199@MON as coating was deposited on stainless steel wires for solid-phase microextraction (SPME) of benzene series (BTEX) in aqueous environments. Under the optimal extraction conditions, the MOF-199@MON coated fiber for SPME coupled with GC-MS for the determination of BTEX gave the linear range of 0.5-500 µg L-1, the limit of detections (LODs, S/N = 3) of 0.01-0.04 µg L-1, the limit of quantifications (LOQs, S/N = 10) of 0.04-0.12 µg L-1, the enhancement factors of 3567-4878, and the intra-day, inter-day and fiber-to-fiber precisions (relative standard deviations, RSDs) of 1.0-9.8, 1.9-7.9 and 4.5-9.5 %, respectively. The developed method was successfully applied to the analysis of BTEX in water samples with the recoveries of 71.0 %-113 %. SIGNIFICANCE: This work reveals the home-made SPME fibers have a long service life (the extraction efficiency of fiber decreased by only 7.26 %-13.14 % after 100 cycles). The potential of MON functionalized MOFs as effective adsorbents for the SPME of pollutants in the water environment.

6.
Cell Prolif ; 57(2): e13540, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37814474

ABSTRACT

Derivation of human hepatocytes from pluripotent stem cells in vitro has important applications including cell therapy and drug discovery. However, the differentiation of pluripotent stem cells into hepatocytes in vitro was not well recapitulated the development of liver. Here, we developed a differentiation protocol by mimicking the two-stage development of hepatoblasts, which permits the efficient generation of hepatic progenitor cells from chemically induced pluripotent stem cells (hCiPSCs). Single-cell RNA sequencing (scRNA-seq) indicates the similarity between hepatoblasts differentiated in vitro and in vivo. Moreover, hCiPSC-derived hepatic progenitor cells can further differentiate into hepatocytes that are similar to primary human hepatocytes with respect to gene expression and key hepatic functions. Our results demonstrate the feasibility of generating hepatic progenitor cells and hepatocytes from hCiPSCs with high efficiency and set the foundation for broad translational applications of hCiPSC-derived hepatocytes.


Subject(s)
Induced Pluripotent Stem Cells , Pluripotent Stem Cells , Humans , Hepatocytes/metabolism , Liver/metabolism , Cell Differentiation
7.
ACS Mater Au ; 3(5): 492-500, 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-38089101

ABSTRACT

Donor-doped melilite materials with interstitial oxygen defects in the structure are good oxide ion conductors with negligible electronic conduction and show great potential in the ceramic electrolyte of intermediate-temperature solid oxide fuel cells (IT-SOFC). However, the parent melilite-structured materials with stoichiometric oxygen are usually insulators. Herein, we reported high and pure oxide ion conduction in the parent K2ZnV2O7 material with a melilite-related structure, e.g., ∼1.14 × 10-3 S/cm at 600 °C, which is comparable to that of the state-of-the-art yttrial-stabilized ZrO2 applied in practical fuel cells. Neutron diffraction data revealed the interesting thermally induced formation of oxygen vacancies at elevated temperatures, which triggered the transformation of the material from electronically conducting to purely and highly oxide ion-conducting. The VO4 tetrahedron with non-bridging terminal oxygen in K2ZnV2O7 was proved to be the key structural factor for transporting oxygen vacancies. The molecular dynamic simulation based on the interatomic potential approach revealed that long-range oxide ion diffusion was achieved by breaking and re-forming the 5-fold MO4 (M = Zn and V) tetrahedral rings. These findings enriched our knowledge of melilite and melilite-related materials, and creating oxygen vacancies in a melilite-related material may be a new strategy for developing novel oxide ion conductors.

8.
Nanoscale Adv ; 5(22): 6017-6037, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-37941954

ABSTRACT

Wound healing is a dynamic and complex process in which the microenvironment at the wound site plays an important role. As a common material for wound healing, dressings accelerate wound healing and prevent external wound infections. Hydrogels have become a hot topic in wound-dressing research because of their high water content, good biocompatibility, and adjustable physical and chemical properties. Intelligent hydrogel dressings have attracted considerable attention because of their excellent environmental responsiveness. As smart polymer hydrogels, thermosensitive hydrogels can respond to small temperature changes in the environment, and their special properties make them superior to other hydrogels. This review mainly focuses on the research progress in thermosensitive intelligent hydrogel dressings for wound healing. Polymers suitable for hydrogel formation and the appropriate molecular design of the hydrogel network to achieve thermosensitive hydrogel properties are discussed, followed by the application of thermosensitive hydrogels as wound dressings. We also discuss the future perspectives of thermosensitive hydrogels as wound dressings and provide systematic theoretical support for wound healing.

9.
Nat Commun ; 14(1): 5933, 2023 09 22.
Article in English | MEDLINE | ID: mdl-37739943

ABSTRACT

Ferroptosis suppressor protein 1 (FSP1, also known as AIMF2, AMID or PRG3) is a recently identified glutathione-independent ferroptosis suppressor1-3, but its underlying structural mechanism remains unknown. Here we report the crystal structures of Gallus gallus FSP1 in its substrate-free and ubiquinone-bound forms. The structures reveal a FAD-binding domain and a NAD(P)H-binding domain, both of which are shared with AIF and NADH oxidoreductases4-9, and a characteristic carboxy-terminal domain as well. We demonstrate that the carboxy-terminal domain is crucial for the catalytic activity and ferroptosis inhibition of FSP1 by mediating the functional dimerization of FSP1, and the formation of two active sites located on two sides of FAD, which are responsible for ubiquinone reduction and a unique FAD hydroxylation respectively. We also identify that FSP1 can catalyze the production of H2O2 and the conversion of FAD to 6-hydroxy-FAD in the presence of oxygen and NAD(P)H in vitro, and 6-hydroxy-FAD directly inhibits ferroptosis in cells. Together, these findings further our understanding on the catalytic and ferroptosis suppression mechanisms of FSP1 and establish 6-hydroxy-FAD as an active cofactor in FSP1 and a potent radical-trapping antioxidant in ferroptosis inhibition.


Subject(s)
Ferroptosis , Hydrogen Peroxide , NAD , Ubiquinone , Catalysis
10.
J Agric Food Chem ; 71(29): 11204-11216, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37440755

ABSTRACT

Bentazone (BNTZ) is a selective and efficient herbicide used in crop production worldwide. However, the persistence of BNTZ residues in the environment has led to their increasing accumulation in farmland and crops, posing a high risk to human health. To evaluate its impact on crop growth and environmental safety, a comprehensive study was conducted on BNTZ toxicity, metabolic mechanism, and resultant pathways in rice. The rice growth was compromised to the treatment with BNTZ at 0.2-0.8 mg/L (529.95-1060.05 g a.i./ha), while the activities of enzymes including SOD, POD, CAT, GST, GT, and CYP450 were elevated under BNTZ stress. A genome-wide RNA-sequencing (RNA-Seq) was performed to dissect the variation of transcriptomes and metabolic mechanisms in rice exposed to BNTZ. The degradative pathways of BNTZ in rice are involved in glycosylation, hydrolysis, acetylation, and conjugation processes catalyzed by the enzymes. Our data provided evidence that helps understand the BNTZ metabolic and detoxic mechanisms.


Subject(s)
Herbicides , Oryza , Humans , Oryza/genetics , Oryza/metabolism , Antioxidants/metabolism , Herbicides/metabolism , Benzothiadiazines/metabolism , Transcriptome
11.
Plant Signal Behav ; 18(1): 2218670, 2023 12 31.
Article in English | MEDLINE | ID: mdl-37288791

ABSTRACT

Adventitious roots (ARs), developing from non-root tissue, play an important role in some plants. Here, the molecular mechanism of AR differentiation in Lotus japonicus L. (L. japonicus) with the transformed chicken interferon alpha gene (ChIFNα) encoding cytokine was studied. ChIFNα transgenic plants (TP) were identified by GUS staining, PCR, RT-PCR, and ELISA. Up to 0.175 µg/kg rChIFNα was detected in TP2 lines. Expressing rChIFNα promotes AR development by producing longer roots than controls. We found that the effect was enhanced with the auxin precursor IBA treatment in TP. IAA contents, POD, and PPO activities associated with auxin regulation were higher than wild type (WT) in TP and exogenous ChIFNα treatment plants. Transcriptome analysis revealed 48 auxin-related differentially expressed genes (DEGs) (FDR < 0.05), which expression levels were verified by RT-qPCR analysis. GO enrichment analysis of DEGs also highlighted the auxin pathway. Further analysis found that ChIFNα significantly enhanced auxin synthesis and signaling mainly with up-regulated genes of ALDH, and GH3. Our study reveals that ChIFNα can promote plant AR development by mediating auxin regulation. The findings help explore the role of ChIFNα cytokines and expand animal gene sources for the molecular breeding of growth regulation of forage plants.


Subject(s)
Indoleacetic Acids , Lotus , Animals , Indoleacetic Acids/metabolism , Lotus/genetics , Lotus/metabolism , Interferon-alpha/genetics , Interferon-alpha/metabolism , Chickens/metabolism , Plant Roots/metabolism , Gene Expression Regulation, Plant/genetics
12.
Biomater Adv ; 151: 213475, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37267749

ABSTRACT

Digital light projection (DLP) printing of hydroxyapatite (HAp) bioceramic provides a promising strategy for fabrication of complex personalized bio-tooth root scaffold with high-resolution. However, it is still a challenge to fabricate bionic bio-tooth root with satisfied bioactivity and biomechanics. This research studied the HAp-based bioceramic scaffold with bionic bioactivity and biomechanics for personalized bio-root regeneration. Compared to natural decellularized dentine (NDD) scaffolds with unitary shape and restricted mechanical properties, those DLP printing bio-tooth roots with natural size, high precision appearance, excellent structure, and a smooth surface were successfully manufactured, which met various shape and structure requirements for personalized bio-tooth regeneration. Moreover, the bioceramic sintering at 1250 °C enhanced the physicochemical properties of HAp and exhibited good elastic modulus (11.72 ± 0.53 GPa), which was almost twice of early NDD (4.76 ± 0.75 GPa). To further improve the surface activity of sintered biomimetic, the nano-HAw (nano-hydroxyapatite whiskers) coating deposited by hydrothermal treatment increased the mechanical properties and surface hydrophilicity, which indicated positive effects on dental follicle stem cells (DFSCs)' proliferation and enhanced the DFSCs osteoblastic differentiation in vitro. Subcutaneous transplantation in nude mice and in-situ transplantation in rat alveolar fossa proved that the nano-HAw-containing scaffold could promote the DFSCs differentiate into periodontal ligament-like enthesis formation. In conclusion, by combining the optimized sintering temperature and modified nano-HAw interface through hydrothermal treatment, the DLP-printing of HAp-based bioceramic with favorable bioactivity and biomechanics is a promising candidate for personalized bio-root regeneration.


Subject(s)
Bionics , Tissue Scaffolds , Mice , Rats , Animals , Tissue Scaffolds/chemistry , Biomechanical Phenomena , Mice, Nude , Durapatite/pharmacology , Durapatite/chemistry , Printing, Three-Dimensional , Regeneration
13.
Chin Med Sci J ; 38(2): 147-158, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37280723

ABSTRACT

Objective To systematically analyze the current status of outcomes reporting in clinical trials on treating stasis acute mastitis with Traditional Chinese Medicine breast massage.Methods We searched CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Embase, Cochrane library, JBI, CINAHL, PsycINFO, Clinical Trials Registry Platform portal, Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, Center Watch Registry from inception to May 15, 2022 to find randomized controlled trials, non-randomized controlled trials, case series and cohort studies which reported the outcomes of stasis acute mastitis managed with Traditional Chinese Medicine breast massage, with search terms of mastitis, acute mastitis, lactation mastitis, puerperal mastitis, breast problem, breast engorgement, milk stasis, blocked ducked, breast pain, breast massage, and acupoint massage. Outcomes and the measurement schemes (measurement methods, timing of assessing outcome, frequency of assessing outcome, measurers) were extracted from the included studies. We used the Management of Otitis Media with Effusion in Children with Cleft Palate (MOMENT) to assess the quality of each study, then categorized outcomes derived from the included studies into different domains according to the Outcome Measures in Rheumatology Arthritis Clinic Trials (OMERACT) Filter 2.1 framework.Results We identified 85 clinical trials, in which 54 different outcomes were reported. A total of 81.2% (69/85) of studies were assessed as medium quality with a mean score of 2.6, and 18.8% (16/85) as low quality with a mean score of 0.9. These outcomes were organized in three core areas. Lump size (89.4%, 76/85) was the most frequently reported outcome, followed by breast pain (69.4%, 59/85) and milk excretion (68.2%, 58/85). Five methods were used to assess lump size and four methods to assess breast pain.Conclusions The outcomes reported in clinical trials regarding stasis acute mastitis treated by Traditional Chinese Medicine breast massage are heterogeneous. Developing a core outcome set to achieve consistent standards for reporting outcomes and modalities for validation of the outcomes is clearly warranted.


Subject(s)
Mastitis , Mastodynia , Child , Female , Humans , Australia , Massage , Mastitis/therapy , Medicine, Chinese Traditional
14.
Biochimie ; 208: 186, 2023 05.
Article in English | MEDLINE | ID: mdl-37225283

ABSTRACT

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Concerns raised by Dr. Sander Kersten in PubPeer pointed out that Figs. 6.1B and 6.2B of this paper were different figures but the legends and Western blots were identical; the quantification was also seen to be different between the two figures. Shortly afterwards, the authors asked to publish a corrigendum for part B of Fig. 6.1, including images of western blots and associated bar plots. Subsequently, the journal conducted an investigation and found evidence that there had been improper manipulation and duplication of images in Fig. 2 E, 6.2 B, 5 A and and 6.2 D, as shown by the reuse of several western blot bands with approximately 180° rotation in each case. After raising the complaint with the authors, the corresponding author agreed that the paper should be retracted. The authors apologise to the readers of the journal.

15.
Langenbecks Arch Surg ; 408(1): 215, 2023 May 29.
Article in English | MEDLINE | ID: mdl-37247018

ABSTRACT

PURPOSE: Transjugular intrahepatic portosystemic shunt (TIPS) and splenectomy with periesophagogastric devascularization (SPD) are widely used to treat cirrhotic portal hypertension (PH) and prevent variceal rebleeding. However, direct comparisons between these two approaches are rare. This study was designed to compare the long-term outcomes of TIPS and SPD in patients with cirrhotic PH and variceal rebleeding. METHODS: The study included cirrhotic PH patients with a history of gastroesophageal variceal bleeding between 18 and 80 years of age who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2012 to January 2022. Patients were enrolled into two groups according to TIPS or SPD was performed. Baseline characteristics were matched using propensity score matching (PSM). RESULTS: A total of 230 patients underwent TIPS, while 184 underwent SPD. PSM was carried out to balance available covariates, resulting in a total of 83 patients in the TIPS group and 83 patients in the SPD group. Patients in SPD group had better liver function during 60 months follow-up. Five-year overall survival rates in SPD group and TIPS group were 72 and 27%, respectively, at 2 years were 88 and 86%, respectively. The 2- and 5-year freedom from variceal rebleeding rates were 95 and 80% in SPD group and 80 and 54% in TIPS group. CONCLUSIONS: SPD is clearly superior to TIPS in terms of OS and freedom from variceal rebleeding in patients with cirrhotic PH. In addition, SPD improved liver function in patients with cirrhotic PH.


Subject(s)
Esophageal and Gastric Varices , Hypertension, Portal , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/surgery , Portasystemic Shunt, Transjugular Intrahepatic/methods , Splenectomy , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Liver Cirrhosis/complications , Liver Cirrhosis/surgery , Hypertension, Portal/complications , Hypertension, Portal/surgery , Chronic Disease
16.
Acta Biochim Biophys Sin (Shanghai) ; 55(4): 661-671, 2023 May 06.
Article in English | MEDLINE | ID: mdl-37154586

ABSTRACT

Despite substantial advances that have been made in understanding the etiology of hepatocellular carcinoma (HCC), the early-stage diagnosis and treatment of advanced-stage HCC remain a major challenge. RNF8, an E3 ligase important for the DNA damage response, has been proven to facilitate the progression of breast and lung cancer, but its role in HCC remains unclear. In this study, we find that the expression of RNF8 is up-regulated in HCC tissues and positively correlated with poor prognosis of HCC. Furthermore, silencing RNF8 by siRNAs attenuates the migration of HCC cells and inhibits epithelial-mesenchymal transition (EMT) by regulating the expressions of proteins including N-cadherin, ß-catenin, snail, and ZO-1. Moreover, Kaplan‒Meier survival analysis shows that high RNF8 expression predicts poor survival benefits from sorafenib. Finally, cell viability assay demonstrates that RNF8 depletion enhances the sensitivity of HCC cells to sorafenib and lenvatinib treatment. We hypothesize that the inhibitory role of RNF8 in EMT and its enhancing effects on anti-cancer drugs orchestrate the protective effects of RNF8 deficiency in HCC, which indicates its potential in clinical application.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Sorafenib/pharmacology , Sorafenib/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , DNA-Binding Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
17.
Pharmaceutics ; 15(2)2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36839784

ABSTRACT

Drug and radiotherapy resistance is the primary cause of treatment failure and poor prognosis in patients with tumors. Exosomes are extracellular vesicles loaded with substances such as nucleic acids, lipids, and proteins that transmit information between cells. Studies have found that exosomes are involved in tumor therapy resistance through drug efflux, promotion of drug resistance phenotypes, delivery of drug-resistance-related molecules, and regulation of anti-tumor immune responses. Based on their low immunogenicity and high biocompatibility, exosomes have been shown to reduce tumor therapy resistance by loading nucleic acids, proteins, and drugs inside xosomes or expressing tumor-specific antigens, target peptides, and monoclonal antibodies on their phospholipid bimolecular membranes. Consequently, future research on genetically engineered exosomes is expected to eliminate resistance to tumor treatment, improving the overall prognosis of patients with tumors.

18.
Fish Shellfish Immunol ; 134: 108579, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36738947

ABSTRACT

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that can recognize pathogen-associated molecular patterns (PMPs) and play important roles in the innate immune system in vertebrates. In this study, we identified a teleost-specific tlr22 gene from yellow catfish (Pelteobagrus fulvidraco) and its immune roles in response to different pathogens were also determined. The open reading frame (ORF) of the tlr22 was 2892 bp in length, encoding a protein of 963 amino acids. Multiple protein sequences alignment, secondary and three-dimensional structure analyses revealed that TLR22 is highly conserved among different fish species. Phylogenetic analysis showed that the phylogenetic topology was divided into six families of TLR1, TLR3, TLR4, TLR5, TLR7 and TLR11, and TLR22 subfamily was clustered into TLR11 family. Meanwhile, synteny and gene structure comparisons revealed functional and evolutionary conservation of the tlr22 gene in teleosts. Furthermore, tlr22 gene was shown to be widely expressed in detected tissues except barbel and eye, with highest expression level in liver. The transcription of tlr22 was significantly increased in spleen, kidney, liver and gill tissues at different timepoints after Poly I:C infection, suggesting TLR22 plays critical roles in defensing virus invasion. Similarly, the transcription of tlr22 was also dramatically up-regulated in spleen, kidney and gill tissues with different patterns after Aeromonas hydrophila infection, indicating that TLR22 is also involved in resisting bacteria invasion. Our findings will provide a solid basis for the investigation the immune functions of tlr22 gene in teleosts, as well as provide useful information for disease control and treatment for yellow catfish.


Subject(s)
Catfishes , Fish Diseases , Animals , Gene Expression Regulation , Aeromonas hydrophila/physiology , Phylogeny , Toll-Like Receptors/genetics , Poly I-C , Fish Proteins/genetics
19.
ACS Appl Mater Interfaces ; 15(4): 5990-5997, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36689469

ABSTRACT

Here, two-dimensional (2D) nitrogen-doped carbon nanosheets (CNSs) were prepared through carbonizing MOFs (ZIF-8) in-situ grown using graphitic carbon nitride (g-C3N4) as a template. The developed ZIF-8 CNS was then used as solid-phase microextraction (SPME) fiber coating for beneficiation of five biomarkers in exhalation of patients with esophageal cancer and in gas chromatography-mass spectrometry (GC-MS) for determination. The ZIF-8 CNS fiber exhibits satisfactory enrichment factors (3490-5631), wide linearity (5-1000 µg L-1), and low detection limits (0.26-0.96 µg L-1). The relative standard deviations (RSDs) for six replicate extractions of the same ZIF-8 CNS fiber were between 2.0-3.9% (intra-day) and 2.8-5.2% (inter-day). The reproducibility of three fibers prepared by the same approach was in the range 6.8-12.3% (RSD). The developed ZIF-8 CNS fiber can persist in 120 SPME cycles with no prominent loss of extraction efficiency and precision. The high enrichment factors of the 2D ZIF-8 CNS coatings are attributed to the high specific surface area, ultrathin thickness, and nano-pore or interlayer channels; moreover, nitrogen doping also endows the π system with a strong electron absorption ability, which will enhance the π-π interaction between the ZIF-8 CNS and the aromatic ring. Ultimately, the self-made ZIF-8 CNS-coated SPME fiber was applied to the analysis of exhaled breath samples. The recoveries of spiked analytes are between 84 and 105%.


Subject(s)
Carbon , Esophageal Neoplasms , Humans , Carbon/chemistry , Nitrogen , Solid Phase Microextraction/methods , Exhalation , Reproducibility of Results
20.
EMBO Rep ; 24(2): e51800, 2023 02 06.
Article in English | MEDLINE | ID: mdl-36382803

ABSTRACT

Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA (dsDNA) sensor that functions in the innate immune system. Upon binding dsDNA, cGAS and dsDNA form phase-separated condensates in which cGAS catalyzes the synthesis of 2'3'-cyclic GMP-AMP that subsequently triggers a STING-dependent, type I interferon (IFN-I) response. Here, we show that cytoplasmic RNAs regulate cGAS activity. We discover that RNAs do not activate cGAS but rather promote phase separation of cGAS in vitro. In cells, cGAS colocalizes with RNA and forms complexes with RNA. In the presence of cytoplasmic dsDNA, RNAs colocalize with phase-separated condensates of cGAS and dsDNA. Further in vitro assays showed that RNAs promote the formation of cGAS-containing phase separations and enhance cGAS activity when the dsDNA concentration is low. Cotransfection of RNA with a small amount of dsDNA into THP1 cells significantly enhances the production of the downstream signaling molecule interferon beta (IFNB). This enhancement can be blocked by a cGAS-specific inhibitor. Thus, cytoplasmic RNAs could regulate cGAS activity by modulating the formation of cGAS-containing condensates.


Subject(s)
Nucleotidyltransferases , RNA , RNA/genetics , Nucleotidyltransferases/genetics , Nucleotidyltransferases/metabolism , Interferon-beta/genetics , DNA/genetics , DNA/metabolism , Signal Transduction/genetics , Immunity, Innate/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...