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1.
Exp Eye Res ; 243: 109905, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38642599

ABSTRACT

Myopia, the most prevalent eye condition, has sparked notable interest regarding its origin and prevention. MicroRNAs (miRNAs) are short, non-coding RNA strands typically consisting of 18-24 nucleotides. They play a central role in post-transcriptional gene regulation and are closely associated with both normal and pathological processes in organisms. Recent advances in next-generation sequencing and bioinformatics have provided novel insights into miRNA expression and its regulatory role in myopia. This review discusses the distinct expression patterns, regulatory functions, and potential pathways of miRNAs involved in the onset and progression of myopia. The primary objective of this review was to provide valuable insights into molecular mechanisms underlying myopia and the contribution of miRNAs. These insights are expected to pave the way for further exploration of the molecular mechanisms, diagnosis, treatment, and clinical applications of myopia.


Subject(s)
Gene Expression Regulation , MicroRNAs , Myopia , Humans , MicroRNAs/genetics , Myopia/genetics , Myopia/metabolism , Myopia/physiopathology
2.
Langmuir ; 40(23): 12017-12026, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38804259

ABSTRACT

This work combined gold colloid probe atomic force microscopy (AFM) with a quartz crystal microbalance (QCM) to accurately quantify the molecular interactions of fluorine-free phosphonium-based ionic liquids (ILs) with gold electrode surfaces. First, the interactions of ILs with the gold electrode per unit area (FA', N/m2) were obtained via the force-distance curves measured by gold probe AFM. Second, a QCM was employed to detect the IL amount to acquire the equilibrium number of IL molecules adsorbed onto the gold electrode per unit area (NIL, Num/m2). Finally, the quantified molecular interactions of ILs with the gold electrode (F0, nN/Num) were estimated. F0 is closely related to the IL composition, in which the IL with the same anion but a longer phosphonium cation exhibits a stronger molecular interaction. The changes in the quantified interactions of gold with different ILs are consistent with the interactions predicted by the extended Derjaguin-Landau-Verwey-Overbeek theory, and the van der Waals interaction was identified as the major contribution of the overall interaction. The quantified molecular interaction is expected to enable the direct experimental-derived interaction parameters for molecular simulations and provide the virtual design of novel ILs for energy storage applications.

3.
Graefes Arch Clin Exp Ophthalmol ; 262(3): 983-990, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37864638

ABSTRACT

Myopia, a common ophthalmic disorder, places a high economic burden on individuals and society. Genetic and environmental factors influence myopia progression; however, the underlying mechanisms remain unelucidated. This paper reviews recent advances in circadian rhythm, intrinsically photosensitive retinal ganglion cells (ipRGCs), and dopamine (DA) signalling in myopia and proposes the hypothesis of a circadian rhythm brain retinal circuit in myopia progression. The search of relevant English articles was conducted in the PubMed databases until June 2023. Based on the search, emerging evidence indicated that circadian rhythm was associated with myopia, including circadian genes Bmal1, Cycle, and Per. In both humans and animals, the ocular morphology and physiology show rhythmic oscillations. Theoretically, such ocular rhythms are regulated locally and indirectly via the suprachiasmatic nucleus, which receives signal from the ipRGCs. Compared with the conventional retinal ganglion cells, ipRGCs can sense the presence of light because of specific expression of melanopsin. Light, together with ipRGCs and DA signalling, plays a crucial role in both circadian rhythm and myopia. In summary, regarding myopia progression, a circadian rhythm brain retinal circuit involving ipRGCs and DA signalling has not been well established. However, based on the relationship between circadian rhythm, ipRGCs, and DA signalling in myopia, we hypothesised a circadian rhythm brain retinal circuit.


Subject(s)
Myopia , Retinal Ganglion Cells , Animals , Humans , Dopamine , Myopia/genetics , Retina , Circadian Rhythm
4.
Acta Biochim Biophys Sin (Shanghai) ; 56(3): 405-413, 2024 03 25.
Article in English | MEDLINE | ID: mdl-38425245

ABSTRACT

RNA terminal phosphorylase B (RTCB) has been shown to play a significant role in multiple physiological processes. However, the specific role of RTCB in the mouse colon remains unclear. In this study, we employ a conditional knockout mouse model to investigate the effects of RTCB depletion on the colon and the potential molecular mechanisms. We assess the efficiency and phenotype of Rtcb knockout using PCR, western blot analysis, histological staining, and immunohistochemistry. Compared with the control mice, the Rtcb-knockout mice exhibit compromised colonic barrier integrity and prominent inflammatory cell infiltration. In the colonic tissues of Rtcb-knockout mice, the protein levels of TNF-α, IL-8, and p-p65 are increased, whereas the levels of IKKß and IκBα are decreased. Moreover, the level of GSK3ß is increased, whereas the levels of Wnt3a, ß-catenin, and LGR5 are decreased. Collectively, our findings unveil a close association between RTCB and colonic tissue homeostasis and demonstrate that RTCB deficiency can lead to dysregulation of both the NF-κB and Wnt/ß-catenin signaling pathways in colonic cells.


Subject(s)
Colitis , NF-kappa B , Animals , Mice , beta Catenin/genetics , beta Catenin/metabolism , Colitis/genetics , Mice, Knockout , NF-kappa B/metabolism , Wnt Signaling Pathway
5.
Langmuir ; 39(17): 5956-5969, 2023 May 02.
Article in English | MEDLINE | ID: mdl-37084536

ABSTRACT

It is significant to understand the interfacial interactions involved between the cellulose acetate (CA) and dispersed nanomaterials, in which the enhanced interaction improves the mechanical behavior of CA. In this work, the amendments of CA with SiO2 nanoparticles have been found to be endowed by grafting varying concentrations (0, 3, 5, and 6%) of octadecyltrichlorosilane (OTS). Aided by SiO2 colloid probe atomic force microscopy (AFM with a probe diameter of 20 µm), the adhesion force between CA and SiO2 is found to be programmable by tuning OTS concentrations functionalized onto SiO2 surfaces. The adhesion forces of 5% OTS-functionalized SiO2 with CA are the strongest, followed by the ones of 0, 3, and 6% OTS, resulting in a smoother and denser morphology on the film with 5% OTS. The AFM-measured approaching force-distance curves have been further compared to predictions by the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory, in which the XDLVO force is summed as the Liftshitz-van der Waals force (FLW), the electrostatic double-layer force (FEL), and the acid-base interaction force (FAB). FLW and FEL do not change significantly with OTS concentrations functionalized onto SiO2. However, FAB is sensitive to the functionalized OTS concentration onto SiO2 and significantly contributes to the interaction force of the composite films with 5% OTS, promoting the formation of a smooth and dense surface feature with a considerable mechanical performance demonstrated by load-displacement curves from a nanoindenter. This is highly encouraging and suggests that nanomaterials can be incorporated into CA to effectively improve their mechanical compatibility by programming the interaction between the CA matrix and nanomaterials.

6.
Diabetes Obes Metab ; 25(5): 1147-1161, 2023 05.
Article in English | MEDLINE | ID: mdl-36655379

ABSTRACT

Dietary salt (NaCl) is essential to an organism's survival. However, today's diets are dominated by excessive salt intake, which significantly impacts individual and population health. High salt intake is closely linked to cardiovascular disease (CVD), especially hypertension, through a number of well-studied mechanisms. Emerging evidence indicates that salt overconsumption may also be associated with metabolic disorders. In this review, we first summarize recent updates on the mechanisms of salt-induced CVD, the effects of salt reduction and the use of salt substitution as a therapy. Next, we focus on how high salt intake can impact metabolism and energy balance, describing the mechanisms through which this occurs, including leptin resistance, the overproduction of fructose and ghrelin, insulin resistance and altered hormonal factors. A further influence on metabolism worth noting is the reported role of salt in inducing thermogenesis and increasing body temperature, leading to an increase in energy expenditure. While this result could be viewed as a positive metabolic effect because it promotes a negative energy balance to combat obesity, caution must be taken with this frame of thinking given the deleterious consequences of chronic high salt intake on cardiovascular health. Nevertheless, this review highlights the importance of salt as a noncaloric nutrient in regulating whole-body energy homeostasis. Through this review, we hope to provide a scientific framework for future studies to systematically address the metabolic impacts of dietary salt and salt replacement treatments. In addition, we hope to form a foundation for future clinical trials to explore how these salt-induced metabolic changes impact obesity development and progression, and to elucidate the regulatory mechanisms that drive these changes, with the aim of developing novel therapeutics for obesity and CVD.


Subject(s)
Cardiovascular Diseases , Humans , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Sodium Chloride, Dietary/adverse effects , Obesity/metabolism , Diet , Energy Metabolism
7.
Langmuir ; 38(37): 11274-11283, 2022 Sep 20.
Article in English | MEDLINE | ID: mdl-36073033

ABSTRACT

Membrane separation is considered one of the most promising CO2/CH4 separation technologies currently available because it is a safe, environment-friendly, and economical method. However, the inability of membrane materials to reconcile the trade-off between permeability and permeation selectivity limits their further applications; moreover, the mechanism underlying this process is unclear, which is mainly determined by the performance of gas adsorption and diffusion. Therefore, this paper describes the effect of gas adsorption and diffusion on membrane separation by assessing the fundamental gas-membrane and gas-gas interactions. Combining molecular simulation methods (Monte Carlo and molecular dynamics simulation) and a thermodynamic model called "linearized nonequilibrium thermodynamic transfer model", we investigate the permeability and permeation selectivity for CO2/CH4 in five carbon-based membranes and propose a general method for screening membrane materials. The interaction-dominated mechanism derived in this work provides new insights into membrane separation and facilitates the screening of high-performance membrane materials.

8.
Langmuir ; 38(48): 14550-14562, 2022 12 06.
Article in English | MEDLINE | ID: mdl-36399765

ABSTRACT

Herein, a highly sensitive volatile organic compound (VOC) gas sensor is demonstrated using immobilized ionic liquid (IL), 1-butyl-3-methylimidazolium hexafluorophosphate, onto surfaces functionalized by the quaternary ammonium group -N+R, -COOH, and -NH2, i.e., N+-IL, COOH-IL, and NH2-IL, respectively. These functional groups ensure highly tunable interactions between the IL and surfaces, efficiently modulating the electrical resistance of the immobilized IL upon exposure to acetone and toluene. The immobilized IL to both acetone and toluene displays significant electronic resistance changes at a concentration of 150 ppm, falling in the order NH2-IL > N+-IL > COOH-IL for acetone while COOH-IL > NH2-IL > N+-IL for toluene. A better gaseous sensing ability is achieved in COOH-IL for toluene than acetone, while this does not hold in the case of NH2-IL and N+-IL surfaces because of the completely different ion structuring of the IL at these functionalized surfaces. The accelerated ion mobility in the IL that is immobilized onto functionalized surfaces is also responsible for the strong gaseous sensing response, which is demonstrated further by the atomic force microscopy-measured smaller friction coefficient. This is highly encouraging and suggests that ILs can be immobilized by a network formed by surface functionalization to easily and cheaply detect VOCs at ppm concentrations.


Subject(s)
Ionic Liquids , Volatile Organic Compounds , Acetone , Toluene , Gases
9.
Phys Chem Chem Phys ; 24(41): 25411-25419, 2022 Oct 27.
Article in English | MEDLINE | ID: mdl-36250344

ABSTRACT

Atomic force microscopy (AFM) with a gold colloid probe modeled as the electrode surface is employed to directly capture the contact resonance frequency of two phosphonium-based ionic liquids (ILs) containing a common anion [BScB]- and differently lengthened cations ([P6,6,6,14]+ and [P4,4,4,8]+). The comparative interfacial studies are performed by creating IL films on the surface of gold, followed by measuring the wettability, thickness of the films, adhesion forces, surface morphology and AFM-probed contact resonance frequency. In addition, the cyclic voltammetry and impedance spectroscopy measurements of the neat ILs are measured on the surface of the gold electrode. The IL with longer cation alkyl chains exhibits a well-defined thin film on the electrode surface and enhanced the capacitance than the shorter chain IL. The AFM contact resonance frequency and force curves reveal that the longer IL prefers to form stiffer ion layers at the gold electrode surface, suggesting the "…anion-anion-cation-cation…" bilayer structure, in contrast, the shorter-chain IL forms the softer cation-anion alternating structure, i.e., "…anion-cation-anion-cation…".

10.
Molecules ; 27(22)2022 Nov 21.
Article in English | MEDLINE | ID: mdl-36432207

ABSTRACT

Tumor cells rely on aerobic glycolysis to support growth and survival, thus require more glucose supply. Glucose transporters GLUTs, primarily GLUT1, are overexpressed in various cancers. Targeting GLUTs has been regarded as a promising anticancer strategy. In this study, we first evaluated 75 potential GLUT1 inhibitors obtained from virtual screening of the NCI chemical library by a high-throughput cell-based method using a fluorescent glucose analogue 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy-d-glucose (2-NBDG) in COS-7 and SKOV3 cells that express high levels of GLUT1. Four compounds, #12, #16, #43 and #69, that significantly inhibited glucose uptake were further evaluated using flow cytometry directly measuring 2-NBDG uptake at the single-cell level and a Glucose Uptake-GloTM assay indirectly measuring 2-deoxy-d-glucose uptake in SKOV3, COS-7 or MCF-7 cells. The inhibitory effect on cancer cell growth was also determined in SKOV3 and MCF-7 cells, and #12 exhibited the best growth inhibitory effect equivalent to a known GLUT1 inhibitor WZB117. Although the anticancer effect of the identified potential GLUT1 inhibitors was moderate, they may enhance the activity of other anticancer drugs. Indeed, we found that #12 synergistically enhanced the anticancer activity of metformin in SKOV3 ovarian cancer cells.


Subject(s)
Antineoplastic Agents , Glucose , Glucose Transporter Type 1 , Biological Transport , Antineoplastic Agents/pharmacology , Flow Cytometry
11.
BMC Cardiovasc Disord ; 21(1): 402, 2021 08 21.
Article in English | MEDLINE | ID: mdl-34418965

ABSTRACT

BACKGROUND: In the treatment of coronary heart disease, target vessel revascularization (TVR) has attracted increasing attention as an efficient means of percutaneous coronary intervention (PCI). The purpose of this study was to explore the association between stent diameter and TVR in patients undergoing PCI. METHODS: This was a secondary retrospective analysis involving patients with PCI with at least one stent implanted. Information was obtained from the Dryad Digital Repository. Multivariable logistic regression models, interaction analyses, subgroup analyses and piecewise linear regression models were used to evaluate the association between stent diameter and TVR. RESULTS: A total of 2522 patients were eventually enrolled in this study, of which 122 (4.8%) had undergone TVR. Significant positive associations were observed between stent diameter and TVR (continuous: odds ratio [OR] 0.485, 95% confidence interval [CI] 0.305-0.773, P = 0.002; categorical variable: T2 vs. T1, OR 0.541, 95% CI 0.348-0.843; T3 vs. T1, OR 0.520, 95% CI 0.334-0.809; P for trend = 0.005). The association remained stable in the fully adjusted model (continuous: OR 0.526, 95% CI 0.306-0.902, P = 0.020; categorical variable: T2 vs. T1, OR 0.510, 95% CI 0.310-0.839; T3 vs. T1, OR 0.585, 95% CI 0.352-0.973; P for trend = 0.042). Among the subgroups of differing clinical presentations, stent diameter was a powerful protective factor for TVR, especially in the delayed PCI group (P for interaction = 0.002). The association was highly consistent across all the other subgroups studied (all P for interaction > 0.05). In the piecewise linear regression model, the need for TVR decreased with an increase in stent diameter when this ranged between 2.5 and 2.9 mm (OR 0.01, 95% CI: 0.01-0.13, P < 0.001). CONCLUSIONS: A large stent diameter is a powerful protective factor for TVR in PCI patients, especially in the delayed PCI group. This "bigger-is-better" protective effect is remarkable in stents with diameter 2.5-2.9 mm.


Subject(s)
Coronary Disease/therapy , Percutaneous Coronary Intervention/instrumentation , Stents , Aged , China , Coronary Disease/diagnostic imaging , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Prosthesis Design , Protective Factors , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
12.
J Nanosci Nanotechnol ; 18(3): 2068-2071, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29448714

ABSTRACT

A green and robust route by in-situ generation of CeO2 beads around the carbon nanotubes (CNTs) in supercritical carbon dioxide (scCO2) was developed in this work to synthesize hollow CeO2 nanobeads with improved catalytic activity for CO oxidation.

13.
Langmuir ; 30(49): 14832-40, 2014 Dec 16.
Article in English | MEDLINE | ID: mdl-25423593

ABSTRACT

The behavior of surface water, especially the adsorption and dissociation characteristics, is a key to understanding and promoting photocatalytic and biomedical applications of titanium dioxide materials. Using molecular dynamics simulations with the ReaxFF force field, we study the interactions between water and five different TiO2 surfaces that are of interest to both experiments and theoretical calculations. The results show that TiO2 surfaces demonstrate different reactivities for water dissociation [rutile (011) > TiO2-B (100) > anatase (001) > rutile (110)], and there is no water dissociation observed on the TiO2-B (001) surface. The simulations also reveal that the water dissociation and the TiO2 surface chemistry change, and the new surface Ti-OH and O-H functional groups affect the orientation of other near-surface water molecules. On the reactive surface, such as the rutile (110) surface, water dissociated and formed new Ti-OH and O-H bonds on the surface. Those functional groups enhanced the hydrogen bond networking with the near-surface water molecules and their configurations. On the nonreactive TiO2-B (001) surface where no molecular or dissociative water adsorption is observed, near-surface water can also form hydrogen bonds with surface oxygen atoms of TiO2, but their distance to the surface is longer than that on the rutile (011) surface.


Subject(s)
Molecular Dynamics Simulation , Titanium/chemistry , Water/chemistry , Surface Properties
14.
Invest Ophthalmol Vis Sci ; 65(1): 49, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38294802

ABSTRACT

Purpose: To elucidate the influence of dopamine receptor 1 (DRD1) on the proliferation of mouse corneal epithelial cells (MCECs) under inflammatory conditions. Methods: In vitro, immortalized MCECs (iMCECs) were treated with IL-1ß, with and without pcDNA3.1_DRD1. Primary MCECs (pMCECs) were exposed to IL-1ß, with and without DRD1 agonist (A68930). Cell proliferation was quantified using the Cell Counting Kit-8 (CCK-8) assay and immunofluorescence staining for Ki-67 and p63. Expression levels of NOD-like receptor protein 3 (NLRP3), IL-1ß, and IL-6 were assessed. To establish a corneal injury model in mice, a 2-mm superficial keratectomy was performed. Either 0.1% A68930 or PBS was topically administered three times daily to the injured eyes for up to 5 days post-injury. Immunofluorescence analysis was employed to evaluate the expression of Ki-67, p63, and CD45 in mouse corneas. Western blotting and real-time quantitative PCR were utilized for quantitative analysis of DRD1, NLRP3, IL-1ß, and IL-6 in mouse corneas. Corneal epithelial regeneration was monitored through fluorescein sodium staining for a duration of up to 5 days following the injury. Results: Overexpression of DRD1 and A68930 promoted MCEC proliferation and suppressed the expression of NLRP3, IL-1ß, and IL-6 in vitro. Topical application of the 0.1% A68930 following mechanical corneal injury in mice led to increased Ki-67 and p63 expression compared to PBS treatment. Furthermore, topical administration of the 0.1% A68930 reduced the expression of CD45, NLRP3, IL-1ß, and IL-6. Analysis with fluorescein sodium indicated accelerated corneal epithelial regeneration in the 0.1% A68930 treatment group. Conclusions: DRD1 treatment counteracts NLRP3-associated inflammation and facilitates epithelial repair of corneal injury.


Subject(s)
Corneal Injuries , Interleukin-6 , Animals , Mice , Fluorescein , Ki-67 Antigen , NLR Family, Pyrin Domain-Containing 3 Protein , Corneal Injuries/drug therapy , Cornea , Inflammation , Interleukin-1beta , NLR Proteins
15.
Front Biosci (Landmark Ed) ; 29(3): 98, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38538261

ABSTRACT

PURPOSE: Numerous studies have emphasised the importance of necroptosis in the malignant progression of colorectal cancer (CRC). However, whether necroptosis-related genes (NRGs) can be used to predict the prognosis of CRC remains to be revealed. METHODS: Patients with CRC were divided into two clusters based on the expression of NRGs, and prognosis was compared between the two clusters. A prognostic model was established based on NRGs, and its predictive efficiency was validated using Kaplan-Meier (K-M) curves, receiver operating characteristic (ROC) curves and a nomogram. Immune infiltration, single-cell and drug sensitivity analyses were used to examine the effects of NRGs on the prognosis of CRC. RESULTS: The prognostic model served as a valid and independent predictor of CRC prognosis. Immune infiltration and single-cell analyses revealed that the unique immune microenvironment of CRC was regulated by NRGs. Drug sensitivity analysis showed that patients in the high- and low-risk groups were sensitive to different drugs. In addition, H2BC18 was found to play an important role in regulating the malignant progression of CRC. CONCLUSION: This study provides novel insights into precision immunotherapy based on NRGs in CRC. The NRG-based prognostic model may help to identify targeted drugs and develop more effective and individualised treatment strategies for patients with CRC.


Subject(s)
Colorectal Neoplasms , Necroptosis , Humans , Prognosis , Necroptosis/genetics , Histones , Gene Expression Profiling , Colorectal Neoplasms/genetics , Tumor Microenvironment/genetics
16.
Food Chem ; 424: 136415, 2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37257279

ABSTRACT

Ethylene, released from fruits and vegetables (F&V) after harvest and during storage, often accelerates the ripening or over-ripening and may be caused decay, leading to substantial economic loss. Dendritic mesoporous silica supported (DMS) platinum (Pt/DMS) catalyst as ethylene scavenger was prepared and various characterization results indicated that the as-prepared Pt/DMS with ultra-low Pt loading exhibited excellent ethylene scavenging performance, which could maintain the complete ethylene conversion (100%) over 50 h at 25 °C and even 0 °C for 100 min with superior consecutive cycles by repeating the use of Pt/DMS. The presence of Pt/DMS delayed banana softening, and browning, reduced weight loss and kept the freshness for 14 days. In conclusion, the active packaging incorporated with Pt/DMS catalysts with high ethylene scavenging efficiency is expected to be extremely beneficial to the post-harvest storage life of other fruits and vegetables that needs further related investigation.


Subject(s)
Musa , Platinum , Silicon Dioxide , Ethylenes , Vegetables
17.
Infect Dis Model ; 8(4): 1108-1116, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37859862

ABSTRACT

COVID-19 has posed formidable challenges as a significant global health crisis. Its complexity stems from factors like viral contagiousness, population density, social behaviors, governmental regulations, and environmental conditions, with interpersonal interactions and large-scale activities being particularly pivotal. To unravel these complexities, we used a modified SEIR epidemiological model to simulate various outbreak scenarios during the holiday season, incorporating both inter-regional and intra-regional human mobility effects into the parameterization scheme. In addition, evaluation metrics were used to evaluate the accuracy of the model simulation by comparing the congruence between simulated results and recorded confirmed cases. The findings suggested that intra-city mobility led to an average surge of 57.35% in confirmed cases of China, while inter-city mobility contributed to an average increase of 15.18%. In the simulation for Tianjin, China, a one-week delay in human mobility attenuated the peak number of cases by 34.47% and postponed the peak time by 6 days. The simulation for the United States revealed that human mobility played a more pronounced part in the outbreak, with a notable disparity in peak cases when mobility was considered. This study highlights that while inter-regional mobility acted as a trigger for the epidemic spread, the diffusion effect of intra-regional mobility was primarily responsible for the outbreak. We have a better understanding on how human mobility and infectious disease epidemics interact, and provide empirical evidence that could contribute to disease prevention and control measures.

18.
J Exp Clin Cancer Res ; 42(1): 219, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37620897

ABSTRACT

BACKGROUND: The Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development. METHODS: MKRN1 expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of MKRN1 on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which MKRN1 regulates CRC metastasis. RESULTS: MKRN1 expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (P < 0.01). MKRN1 downregulation inhibits CRC cell proliferation, migration, and invasion. Conversely, MKRN1 overexpression promotes the proliferation, migration, and invasion of CRC cells. Mechanistically, MKRN1 induces epithelial-mesenchymal transition (EMT) in CRC cells via ubiquitination and degradation of Smad nuclear-interacting protein 1 (SNIP1). Furthermore, SNIP1 inhibits transforming growth factor-ß (TGF-ß) signalling, and MKRN1 promotes TGF-ß signalling by degrading SNIP1 to induce EMT in CRC cells. Finally, using conditional knockout mice, intestinal lesions and metastatic liver microlesions were greatly reduced in the intestinal knockout MKRN1 group compared to that in the control group. CONCLUSIONS: High MKRN1 levels promote TGF-ß signalling through ubiquitination and degradation of SNIP1, thereby facilitating CRC metastasis, and supporting MKRN1 as a CRC pro-cancer factor. The MKRN1/SNIP1/TGF-ß axis may be a potential therapeutic target in CRC.


Subject(s)
Colorectal Neoplasms , RNA-Binding Proteins , Ribonucleoproteins , Animals , Mice , Cell Line , Cell Proliferation , Colorectal Neoplasms/genetics , Proteolysis , Humans , Ribonucleoproteins/metabolism , RNA-Binding Proteins/genetics , Transforming Growth Factor beta/metabolism , Signal Transduction
19.
Langmuir ; 28(43): 15270-7, 2012 Oct 30.
Article in English | MEDLINE | ID: mdl-23046057

ABSTRACT

A simple physical strategy to reduce the frictional and adhesive forces on TiO(2) films was proposed by constructing mesoporous TiO(2) films with heterogeneously distributed nanopores on the film surfaces. In comparison, TiO(2) films with densely packed nanoparticles were also prepared. The crystal structure and morphology of the films were characterized with Raman spectroscopy, field emission scanning electron microscopy (FESEM), and atomic force microscopy (AFM). It was found that the TiO(2)(B) phase exists in the mesoporuos TiO(2) films but not in the densely packed films. The existence of TiO(2)(B) plays a significant role in creating and maintaining the nanopores in the mesoporous TiO(2) films. The frictional and adhesive forces were measured on both films using AFM. The mesoporous films exhibit two typical adhesion forces of around 3 and 12 nN in the force distribution profile whereas the densely packed films show only one around 12 nN. The frictional coefficients were 2.6 × 10(-3) and 6.7 × 10(-2) for the mesoporous and densely packed TiO(2) films, respectively. A model based on the atomic structures of a thin film of water molecules adsorbed on TiO(2) surfaces leading to hydrophobic effects was proposed to understand the lower frictional and adhesive forces observed on the mesoporous TiO(2) films. This simple physical approach to reducing the frictional and adhesive forces on TiO(2) films could have broad applications to a variety of surface coatings.


Subject(s)
Biocompatible Materials/chemistry , Friction , Nanopores , Nanotechnology/methods , Titanium/chemistry , Adhesiveness , Hydrophobic and Hydrophilic Interactions
20.
Stem Cell Res Ther ; 13(1): 237, 2022 06 07.
Article in English | MEDLINE | ID: mdl-35672801

ABSTRACT

BACKGROUND: Stem cell transplantation may improve visual acuity in patients with dry age-related macular degeneration. Herein, we aimed to summarise the evidence on the risks and benefits of stem cell transplantation for improving visual acuity, including the risk of adverse events. METHODS: Data were obtained from the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and each database was interrogated from the date of inception until 19 March 2022. The rates of visual acuity outcomes and adverse events associated with stem cell transplantation were examined. All statistical analyses were conducted using Review Manager 5.4. The study was registered with PROSPERO (CRD 42022322902). RESULTS: The analysis examined 10 studies (102 patients), including one and three, randomised and non-randomised clinical trials, and one and five, multicentre prospective and prospective clinical trials, respectively. Meta-analysis showed changes in best-corrected visual acuity in the study eyes after stem cell transplantation (6 months: risk ratio [RR] = 17.00, 95% confidence interval [CI] 6.08-47.56, P < 0.00001; 12 months: RR = 11.00, 95% CI 2.36-51.36, P = 0.002). Subgroup analysis showed that different stem cell types achieved better best-corrected visual acuity at post-operative 6 months, compared to that observed at baseline. Four cases of related ocular adverse events and no related systemic adverse events were reported. CONCLUSION: This meta-analysis suggests that stem cell transplantation may improve best-corrected visual acuity in dry age-related macular degeneration, based on small sample sizes and fewer randomised controlled trials.


Subject(s)
Macular Degeneration , Humans , Macular Degeneration/therapy , Prospective Studies , Stem Cell Transplantation/adverse effects , Visual Acuity
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