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1.
Transl Res ; 269: 14-30, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38453052

ABSTRACT

The progression of chronic kidney disease (CKD) often involves renal interstitial fibrosis (RIF) and subsequent loss of peritubular capillaries (PTCs), which enhances disease severity. Despite advancements in our understanding of fibrosis, effective interventions for reversing capillary loss remain elusive. Notably, RIF exhibits reduced capillary density, whereas renal cell carcinoma (RCC) shows robust angiogenesis under hypoxic conditions. Using RNA sequencing and bioinformatics, we identified differentially expressed genes (DEGs) in hypoxic human renal tubular epithelial cells (HK-2) and renal cancer cells (786-0). Analysis of altered Ras and PI3K/Akt pathways coupled with hub gene investigation revealed RAS protein activator-like 2 (RASAL2) as a key candidate. Subsequent in vitro and in vivo studies confirmed RASAL2's early-stage response in RIF, which reduced with fibrosis progression. RASAL2 suppression in HK-2 cells enhanced angiogenesis, as evidenced by increased proliferation, migration, and branching of human umbilical vein endothelial cells (HUVECs) co-cultured with HK-2 cells. In mice, RASAL2 knockdown improved Vascular endothelial growth factor A (VEGFA) and Proliferating cell nuclear antigen (PCNA) levels in unilateral ureteral occlusion (UUO)-induced fibrosis (compared to wild type). Hypoxia-inducible factor 1 alpha (HIF-1α) emerged as a pivotal mediator, substantiated by chromatin immunoprecipitation (ChIP) sequencing, with its induction linked to activation. Hypoxia increased the production of RASAL2-enriched extracellular vesicles (EVs) derived from tubular cells, which were internalized by endothelial cells, contributing to the exacerbation of PTC loss. These findings underscore RASAL2's role in mediating reduced angiogenesis in RIF and reveal a novel EV-mediated communication between hypoxic tubular- and endothelial cells, demonstrating a complex interplay between angiogenesis and fibrosis in CKD pathogenesis.


Subject(s)
Fibrosis , Humans , Animals , Mice , Male , Human Umbilical Vein Endothelial Cells/metabolism , Microvascular Rarefaction/metabolism , Microvascular Rarefaction/pathology , Microvascular Rarefaction/genetics , Mice, Inbred C57BL , Kidney/blood supply , Kidney/pathology , Kidney/metabolism , Hypoxia/pathology , Hypoxia/metabolism , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Renal Insufficiency, Chronic/genetics , Cell Hypoxia , Kidney Tubules/pathology , Kidney Tubules/metabolism , Cell Line , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/genetics
2.
Cell Tissue Res ; 395(3): 285-297, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38353742

ABSTRACT

Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300 µM H2O2 for 8 h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H2O2-induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H2O2-stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H2O2-induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H2O2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.


Subject(s)
Hypogonadism , MicroRNAs , RNA, Long Noncoding , Animals , Humans , Male , Mice , Apoptosis , Cell Proliferation/genetics , Hydrogen Peroxide , Hypogonadism/genetics , In Situ Hybridization, Fluorescence , Leydig Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Competitive Endogenous , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Small Interfering/metabolism , Sirtuin 1/genetics , Testosterone/pharmacology
3.
Front Genet ; 15: 1197151, 2024.
Article in English | MEDLINE | ID: mdl-38380423

ABSTRACT

Background and aims: Defective enzymes, cofactors, or transporters of metabolic pathways cause inherited metabolic disorders (IMDs), a group of genetic disorders. Several IMDs have serious consequences for the affected neonates. Newborn screening for IMDs is conducted by measuring specific metabolites between 3 and 7 days of life. Herein, we analyzed the incidence, spectrum, and genetic characteristics of IMDs in newborns in the Zhuzhou area. Methods: Tandem mass spectrometry was conducted on 90,829 newborns who were admitted to the Women and Children Healthcare Hospital of Zhuzhou and requested for screening for IMDs. These newborns were subsequently subjected to next-generation sequencing and further validated using Sanger sequencing. Results: 30 IMDs cases were found in 90,829 cases of newborns screened for IMDs, and the overall incidence was 1/3,027. The incidence of amino acid, organic acid, fatty acid oxidation and urea cycle disorders were 1/8,257, 1/18,165, 1/7,569, and 1/45,414, respectively. Additionally, 9 cases of maternal IMDs were found in our study, and unreported gene mutations of 3 cases IMDs were identified. Conclusion: Our data indicated that IMDs are never uncommon in zhuzhou, meanwhile, we also found that primary carnitine deficiency was the only disorder of fatty acid oxidation in Zhuzhou, and the incidence (1/7,569) was higher than the national level, organic acid metabolic diseases are mostly inherited. Therefore, our study has clarified the disease spectrum and genetic backgrounds, contributing to the treatment and prenatal genetic counseling of these disorders in this region.

4.
Inorg Chem ; 63(10): 4770-4782, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38409795

ABSTRACT

Photocatalytic for hydrogen peroxide (H2O2) production is thought as a promising technology owing to its clean and green properties with the cheap and easily available raw materials of H2O and O2. Herein, Pt/g-C3N4 Schottky junction photocatalysts with ultralow Pt contents (0.025-0.1 wt %) were successfully fabricated by an impregnation-reduction method. It can efficiently reduce O2 to generate H2O2 without a sacrificial agent under visible-light irradiation. The yield of H2O2 produced over Pt0.05/g-C3N4 with the optimal 0.05 wt % Pt reached 31.82 µM, which was 2.46 times that of g-C3N4 and higher than most of those in the literature. It also showed good stability in three repeated tests. The deposition of highly dispersed metal Pt nanoparticles with low and limited content can expose enough active Pt atoms, significantly enhance the separation efficiency of photogenerated carriers, and reduce its negative effect on H2O2 decomposition, resulting in improved and outstanding efficiency of H2O2 production. The ·O2- radicals were found to be the main active species. The mechanism of photocatalytic H2O2 production was confirmed to be a two-step single electron route (O2 + e-→ ·O2- → H2O2).

5.
J Colloid Interface Sci ; 660: 423-439, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38244508

ABSTRACT

In this paper, the effect of three monocarboxylic acids on MIL-125 synthesis was systematically investigated and the results were discussed in detail. X-ray diffractometry (XRD) and nitrogen adsorption-desorption curves indicated that small molecule acids (acetic acid, propionic acid and butyric acid) affected the morphology of MIL-125 and induced lamellar pores and structural defects in the crystals. Thermogravimetric measurements confirmed the presence of acid-regulated defective metal-organic frameworks (MOFs). Electrochemical tests and density function theory calculations indicated that acid modulation could change the forbidden bandwidth of the material. The acid modification strategy effectively promoted the transfer of photogenerated electrons and enhanced the adsorption and activation of O2 and H2O molecules, generating reactive radicals. The modified MOFs also showed excellent performance in the removal of mixed toluene and chlorobenzene. The degradation pathways of the mixture were analyzed by in situ infrared (IR) and gas chromatography-mass spectrometry (GC-MS). The mixture was converted to chlorophenolic intermediates in the presence of reactive oxygen species, further decomposed to form ethers and ethanol, and finally formed small molecules such as carbon dioxide and water. A feasible method was provided for the preparation of photocatalysts for the treatment of mixed VOCs.

6.
Sci Rep ; 13(1): 19611, 2023 11 10.
Article in English | MEDLINE | ID: mdl-37949939

ABSTRACT

Renal interstitial fibrosis (RIF) is a key feature of progressive chronic kidney disease (CKD), characterized by tubular epithelial cell (TEC) hypoxia and peritubular capillary (PTC) rarefaction. However, the mechanisms underlying these processes remain poorly understood. To address this knowledge gap, we conducted a comparative transcriptome analysis of hypoxic and normoxic HK-2 cells, identifying 572 differentially expressed genes (DEGs). Subsequent Gene Ontology (GO), protein‒protein interaction (PPI) network, and hub gene analyses revealed significant enrichment of DEGs in the HIF-1 signaling pathway based on KEGG enrichment analysis. To further explore TEC modulation under hypoxic conditions, we performed chromatin immunoprecipitation (ChIP) sequencing targeting HIF-1α, identifying 2915 genes potentially regulated by HIF-1α. By comparing RNA sequencing and ChIP sequencing data, we identified 43 overlapping DEGs. By performing GO analysis and peak annotation with IGV, we identified two candidate molecules, VEGFA and BTG1, that are associated with angiogenesis and whose gene sequences were reliably bound by HIF-1α. Our study elucidates the molecular mechanisms underlying RIF, providing valuable insights for potential therapeutic interventions.


Subject(s)
Microvascular Rarefaction , Humans , Protein Interaction Maps/genetics , Gene Expression Profiling , Hypoxia/genetics , Computational Biology , Fibrosis
7.
J Environ Sci (China) ; 134: 21-33, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37673530

ABSTRACT

The construction of heterophase junctions by rutile-anatase TiO2 is considered an effective strategy for toluene degradation, but the photogenerated electron utilization is still insufficient. In this study, the formation of type-II heterojunction by the encapsulation of Materials of Institut Lavoisier (MIL-101) by anatase is performed, and then the heterophase junction is further constructed to improve the catalytic performance of the photocatalyst. The enhancement of photocatalytic performance depends on the encapsulation of MIL-101 by anatase, the light absorption capacity of anatase, and the contact area of two heterojunctions. Photogenerated electrons are transferred to oxygen vacancies of anatase and promoting the generation of oxygen-containing radicals. The material certifies the synergistic effect of the heterophase junction and heterojunction design and provides a theoretical basis for application in the degradation of volatile organic compounds.


Subject(s)
Gases , Oxygen , Reactive Oxygen Species , Toluene
8.
J Colloid Interface Sci ; 651: 424-435, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37549527

ABSTRACT

The severe hazards on ecological environment and human body caused by volatile organic compounds (VOCs) have attracted worldwide substantial attention. In this research, a series of novel modified Universitetet i Oslo-67 (UiO-67) with water resistance were prepared and characterized, which had modified by benzoic acid and dopamine hydrochloride (67-ben-DH). On this basis, the adsorption performance, adsorption kinetics, defect engineering and water resistance of adsorbent were investigated. The results indicated that the excellent pore structure and specific surface area of 67-ben-DH-6 (molar ratio of Zr4+ to DH was 1:6) were retained while the adsorption performance and water resistance of the adsorbent were improved. Due to more defects, excellent adsorption diffusion and strong π-π interactions of 67-ben-DH-6, it performed the maximum adsorption capacity of toluene (793 mg g-1). Furthermore, the outstanding water resistance was attributed to the fact that N element of DH reduced the affinity of the adsorbent with water. Finally, the density functional theory (DFT) calculations showed that the adsorbent 67-ben-DH-6 had the maximum adsorption energy for toluene (-99.4 kJ mol-1) and the minimum adsorption energy for water (-17.8 kJ mol-1). Thus, the potential mechanism of 67-ben-DH for efficient toluene adsorption and water resistance was verified from a microscopic perspective.

9.
J Hazard Mater ; 437: 129372, 2022 Sep 05.
Article in English | MEDLINE | ID: mdl-35728314

ABSTRACT

Although several strategies have been developed to improve the efficiency of heterogeneous Fenton-like reactions, investigating the relationship among the electronic properties of the catalyst surface, the complex water matrix and catalytic activity remains challenges. Herein, the electron density of the active site Co(II) in Co Prussian blue analogs (Co-PBAs) is proved to be modulated by the anion source method. The elevated electron density of Co(II) and the higher metallicity of the catalyst lead to an increase in electron transport efficiency as revealed by X-ray photoelectron spectra (XPS), Fourier transform infrared spectroscopy (FT-IR), and density functional theory (DFT) calculations. Furthermore, the negative shift of the D-band center of Co(II) can effectively release intermediates to avoid catalyst poisoning. Bicarbonate has been demonstrated to activate peroxymonosulfate (PMS) by weakening the peroxide bond. Its activation mechanism involves free radical mechanism and non-radical mechanism: the first step is the generation of HCO4-, then it is further hydrolyzed to generate •OH and 1O2, and the other is HCO4- interact with Co(III) to form Co(IV)=O. In addition, the degradation pathways of target contaminants p-nitrophenol and toxicity verification of intermediate products have been investigated. This study provides guidance for the research of Fenton-like reactions.

10.
Mol Cytogenet ; 15(1): 15, 2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35361246

ABSTRACT

BACKGROUND: Ring chromosomes can be formed by terminal breaks of two arms of a chromosome and their rejoining, leading to a loss of genetic material. They may also be formed by telomere-telomere fusions with no deletion, resulting in the formation of a complete ring. Mosaic X-ring chromosomes are extremely rare and have highly variable phenotypes. Here, we report a case with a mosaic X-ring chromosome in a patient with Turner syndrome, and we illustrate the unreported complicated mechanism using chromosome analysis and fluorescence in situ hybridization (FISH). CASE PRESENTATION: A 10-year-old girl of short stature presenting Turner syndrome was admitted to our hospital. The patient's clinical characteristics were subsequently documented. Genetic analysis showed a karyotype of mostly 45,X[140]/46,X,r(X)[60]. The X ring chromosome was cytogenetically characterized as 45,X/46,X,r(X)(p22.32q21.1), with a length of approximately 74 Mb. CONCLUSIONS: Taken together, we report a rare case with a mosaic X ring chromosome in Turner syndrome and we believe this case expands our collective knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling for Turner syndrome.

11.
J Environ Manage ; 308: 114664, 2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35149402

ABSTRACT

The large amount of trace organic contaminants (TrOCs) in wastewater has caused serious impacts on human health. In the past few years, Sulfate radical (SO4•-) based advanced oxidation processes (SR-AOPs) are widely recognized for their high removal rates of recalcitrant TrOCs from water. Peroxymonosulfate (PMS) and persulfate (PS) are stable and non-toxic strong oxidizing oxidants and can act as excellent SO4•- precursors. Compared with hydroxyl radicals(·OH)-based methods, SR-AOPs have a series of advantages, such as long half-life and wide pH range, the oxidation capacity of SO4•- approaches or even exceeds that of ·OH under suitable conditions. In this review, we present the progress of activating PS/PMS to remove TrOCs by different methods. These methods include activation by transition metal, ultrasound, UV, etc. Possible activation mechanisms and influencing factors such as pH during the activation are discussed. Finally, future activation studies of PS/PMS are summarized and prospected. This review summarizes previous experiences and presents the current status of SR-AOPs application for TrOCs removal. Misconceptions in research are avoided and a research basis for the removal of TrOCs is provided.


Subject(s)
Water Pollutants, Chemical , Humans , Oxidation-Reduction , Sulfates , Technology , Water Pollutants, Chemical/analysis
12.
Hum Cell ; 35(1): 83-97, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34585365

ABSTRACT

Evidence has shown that mesenchymal stem cells' (MSCs) therapy has potential application in treating chronic kidney disease (CKD). In addition, MSCs-derived exosomes can improve the renal function and prevent the progression of CKD. However, the mechanisms by which MSCs-derived exosomes (MSCs-Exo) ameliorate renal fibrosis in CKD remain largely unclear. To mimic an in vitro model of renal fibrosis, rat kidney tubular epithelial cells (NRK52E) were stimulated with transforming growth factor (TGF)-ß1. In addition, we established an in vivo model of unilateral ureteric obstruction (UUO)-induced renal fibrosis. Meanwhile, we exploited exosomes derived from MSCs for delivering miR-186-5p agomir into NRK52E cells or kidneys in vitro and in vivo. In this study, we found that level of miR-186-5p was significantly downregulated in TGF-ß1-stimulated NRK52E cells and the obstructed kidneys of UUO mice. In addition, miR-186-5p can be transferred from MSCs to NRK52E cells via exosomes. MSCs-delivered miR-186-5p markedly reduced the accumulation of extracellular matrix (ECM) protein, and inhibited epithelial-to-mesenchymal transition (EMT) and apoptosis in TGF-ß1-stimulated NRK52E cells. Moreover, exosomal miR-186-5p from MSCs attenuated kidney injury and fibrosis in a UUO mouse model via inhibition of the ECM protein accumulation and EMT process. Meanwhile, dual-luciferase assay showed that miR-186-5p downregulated Smad5 expression via direct binding with the 3'-UTR of Smad5. Collectively then, these findings indicated that exosomal miR-186-5p derived from MSCs could attenuate renal fibrosis in vitro and in vivo by downregulation of Smad5. These findings may help to understand the role of MSCs' exosomes in alleviating renal fibrosis in CKD.


Subject(s)
Exosomes/transplantation , Kidney/pathology , Mesenchymal Stem Cells/cytology , MicroRNAs/administration & dosage , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/therapy , Animals , Apoptosis/genetics , Cells, Cultured , Disease Models, Animal , Down-Regulation/genetics , Epithelial-Mesenchymal Transition/genetics , Extracellular Matrix Proteins/metabolism , Fibrosis , Mice , MicroRNAs/metabolism , Rats , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/pathology , Smad5 Protein/genetics , Smad5 Protein/metabolism , Ureteral Obstruction/complications
13.
J Colloid Interface Sci ; 606(Pt 2): 1811-1822, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34507172

ABSTRACT

Highly dispersed Pt nanoparticles supported UiO-66 catalysts were successfully prepared by the incipient wetness impregnation method. Their thermal catalytic performances were evaluated by toluene degradation. The physicochemical properties of the samples were characterized using a series of characterization methods. The catalytic activity of catalysts remained essentially unchanged in the high weight hourly space velocity, stability and water resistance test, which also indicated good catalytic performance. In the reusability test, the catalytic performance was found to be enhanced after the reaction, because of the catalyst might follow a Pt0-PtO synergistic catalytic mechanism (similar to Mars-van Krevelen mechanism) and there was a phase transition between Pt0 and PtO during the reaction. Firstly, the toluene adsorbed on the catalyst surface was oxidized by the activated lattice oxygen of the PtO. Then, consumption of oxygen atoms led to formation of oxygen vacancies, and finally the molecular oxygen adsorbed by Pt0 was activated and passed to the PtO to supplement the oxygen vacancies, forming a redox cycle. In addition, the possible catalytic oxidation mechanism of toluene was also revealed.

14.
J Hazard Mater ; 424(Pt D): 127640, 2022 02 15.
Article in English | MEDLINE | ID: mdl-34753650

ABSTRACT

Tetracycline (TC) is a commonly used antibiotic that has gained wide spread notoriety owing to its high environmental risks. In this study, rich carbonyl-modified carbon-coated Fe0 was obtained by pyrolysis of MIL-100(Fe) in an Ar atmosphere, and used to activate peroxymonosulfate (PMS) for the degradation of tetracycline in water. The roles of Fe0, carbon and surface carbonyl on PMS activation were investigated. Fe0 continuously activated PMS, acted as a sustained-release source of Fe2+, and could effectively activate PMS to produce SO4•-, O2•- and •OH. Carbon was found to do responsible for electron transportation during the activation of PMS and slow down the oxidation of Fe0. The carbonyl group on the carbon surface layer was the active site of 1O2, which explains the enhanced performance for TC degradation. When Ca = 0.1 g/L and C0 = 0.4 mM, TC degradation rate reached 96%, which was attributed to the synergistic effect of radicals (i.e., SO4•-, O2•-, •OH) and non-radical (i.e., 1O2). Finally, the degradation pathway was proposed by combining density functional theory (DFT) calculations with liquid chromatography-mass spectrometry (LC-MS), toxicities of the intermediate products were also evaluated. All results show that carbonyl-modified carbon-coated Fe0 possesses promising capacity for the removal of antibiotics from water.


Subject(s)
Metal-Organic Frameworks , Anti-Bacterial Agents , Carbon , Peroxides , Tetracycline
15.
J Colloid Interface Sci ; 608(Pt 3): 2884-2895, 2022 Feb 15.
Article in English | MEDLINE | ID: mdl-34802757

ABSTRACT

P-nitrophenol (PNP), a widely used compound, is harmful to the environment and human health. In this study, four iron-based Prussian blue analogs (PBAs) were prepared by coprecipitation (Co-Fe PBA, Mn-Fe PBA, Cu-Fe PBA and Fe-Fe PBA). The Co-Fe PBA exhibited high peroxymonosulfate (PMS) activation performance for PNP degradation, removing over 90% of PNP in 60 min at an optimal pH of 7, temperature at 30 ℃, initial concentration of 20 mg/L, PBA dose of 0.2 g/L and PMS dose of 1 g/L. The physicochemical properties of the Co-Fe PBA were investigated by various characterization methods. The catalytic activity of PBA and the influence of various process parameters and water quality on the catalytic reaction were investigated to elucidate the mechanism of p-nitrophenol degradation by PBA-activated persulfate. Moreover, the mechanism of accelerated degradation of PNP under HCO3- conditions and the role of major reactive oxides were determined by EPR measurement methods and free radical trapping experiments. HCO3- was found to directly activate PMS to produce reactive oxygen species, and 1O2, ∙OH and SO4∙- were all greatly increased. This work presents a promising green heterogeneous catalyst for the degradation of emerging contaminants (ECs) in real wastewater with natural organic matter and coexisting anions by PMS activation.


Subject(s)
Bicarbonates , Iron , Ferrocyanides , Humans , Nitrophenols , Peroxides
16.
Aging (Albany NY) ; 13(20): 23769-23779, 2021 10 25.
Article in English | MEDLINE | ID: mdl-34695807

ABSTRACT

Renal hypoxia is associated with persisting peritubular capillary rarefaction in progression of chronic kidney disease (CKD), and this phenomenon mainly resulted from the dysregulated angiogenesis. Rab7 is known to be involved in renal hypoxia. However, the mechanism by which Rab7 regulates the renal hypoxia remains unclear. Protein expression was detected by western blot. Cell proliferation was detected by EdU staining. Cell migration was tested by transwell assay. Rab7 was upregulated in HK-2 cells under hypoxia conditions. Hypoxia significantly inhibited the viability and proliferation of human microvascular endothelial cells (HMEC-1 cells), while this phenomenon was obviously reversed by Rab7 silencing. Consistently, Hypoxia significantly decreased the migration and tube length of HMECs, which was partially reversed by knockdown of Rab7. Moreover, hypoxia-induced inhibition of MMP2 activity was significantly rescued by knockdown of Rab7. Moreover, ARP100 (MMP-2 inhibitor) significantly reversed the effect of Rab7 shRNA on cell viability, migration and angiogenesis. Furthermore, knockdown of Rab7 significantly alleviated the fibrosis in tissues of mice. Knockdown of Rab7 significantly alleviated the renal hypoxia in chronic kidney disease through regulation of MMP-2. Thus, our study might shed new light on exploring the new strategies against CKD.


Subject(s)
Cell Hypoxia , Matrix Metalloproteinase 2 , Neovascularization, Pathologic/genetics , rab7 GTP-Binding Proteins , Animals , Cell Hypoxia/genetics , Cell Hypoxia/physiology , Cell Line , Cell Movement/genetics , Epithelial Cells/metabolism , Humans , Kidney Tubules/cytology , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Mice , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , rab7 GTP-Binding Proteins/genetics , rab7 GTP-Binding Proteins/metabolism
18.
Biochim Biophys Acta Rev Cancer ; 1875(1): 188492, 2021 01.
Article in English | MEDLINE | ID: mdl-33321174

ABSTRACT

Protein arginine deiminases (PADs), is a group of calcium-dependent enzymes, which play crucial roles in citrullination, and can catalyze arginine residues into citrulline. This chemical reaction induces citrullinated proteins formation with altered structure and function, leading to numerous pathological diseases, including inflammation and autoimmune diseases. To date, multiple studies have provided solid evidence that PADs are implicated in cancer progression. Nevertheless, the findings on PADs functions in tumors are too complex to understand due to its involvements in variable signaling pathways. The increasing interest in PADs has heightened the need for a comprehensive description for its role in cancer. The present study aims to identify the gaps in present knowledge, including its structures, biological substrates and tissue distribution. Since several irreversible inhibitors for PADs with good potency and selectivity have been explored, the mechanisms on the dysregulation in tumors remain poorly understood. The present study discusses the relationship between PADs and tumor apoptosis, EMT formation and metastasis as well as the implication of neutrophil extracellular traps (NETs) in tumorigenesis. In addition, the potential uses of citrullinated antigens for immunotherapy were proposed.


Subject(s)
Citrullination/genetics , Epithelial-Mesenchymal Transition/genetics , Neoplasms/genetics , Protein-Arginine Deiminases/genetics , Citrulline/genetics , Citrulline/metabolism , Extracellular Traps/genetics , Humans , Neoplasms/pathology , Signal Transduction/genetics
19.
J Gastric Cancer ; 20(3): 300-312, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33024586

ABSTRACT

PURPOSE: Circular RNAs (circRNAs) are a new class of RNA molecules whose function is largely unknown. There is a growing evidence that circRNAs play an important regulatory role in the progression of a variety of human cancers. However, the exact roles and the mechanisms of circRNAs in gastric cancer are not clear. In this study, we aimed to elucidate the mechanism of hsa_circ_0005556. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction was used to detect the expression of hsa_circ_0005556, miR-4270, and matrix metalloproteinase-19 (MMP19) in gastric cancer tissues and cell lines. The expression of hsa_circ_0005556 in gastric cancer cells was silenced by lentivirus, and cell proliferation, invasion, migration, and tumorigenesis in nude mice were assessed to evaluate the function of hsa_circ_0005556 in gastric cancer. RESULTS: The expression of hsa_circ_0005556 in gastric cancer tissues and gastric cancer cell lines was higher compared to normal controls. In vitro, the downregulation of hsa_circ_0005556 significantly inhibited proliferation, migration, and invasion of gastric cancer cells. In vivo, the downregulation of hsa_circ_0005556 suppressed tumor growth in nude mice. CONCLUSIONS: Our study shows that the hsa_circ_0005556/miR-4270/MMP19 axis is involved in proliferation, migration, and invasion of gastric cancer cells through the competing endogenous RNA (ceRNA) mechanism.

20.
J Hazard Mater ; 399: 123070, 2020 11 15.
Article in English | MEDLINE | ID: mdl-32540708

ABSTRACT

Perfluorooctanoic acid (PFOA), a widely used compound, is harmful to the environment and human health. In this study, a facile one pot solvothermal method of integrating BiOCl with Zn-Al hydrotalcite to form spherical-shaped BiOCl/Zn-Al hydrotalcite (B-BHZA) sample is reported. The characteristics and main factors affecting photocatalytic PFOA and photocatalytic mechanism of BiOCl/Zn-Al hydrotalcite (B-BHZA) are systematically investigated. It is found that spherical-shaped B-BHZA possesses abundant defects and a larger surface area of 64.4 m2 g-1. The factors affecting photocatalytic removal PFOA (e.g., time, pH, initial concentration and dosage) are investigated by modeling the 3D surface response. The removal rate of PFOA is over 90 % in 6 h under UV light at an optimal pH of 2, an initial concentration of 500 µg/L and a dose of dosage 0.5 g/L. The main mechanism occurs by photo-generated h+ oxidation and synergistic effects from the photocatalysis process. Though investigating the intermediates of PFOA degradation and F-, a possibility was proposed that h+ initiated the rapidly decarboxylation of PFOA. The unstable perfluoroheptyl group is formatted and further conversed to short chain perfluorocarboxylic acid. This study provides a new insight for the preparation of highly efficient photocatalysts to the treatment of halogenated compounds in UV system.

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