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1.
Angew Chem Int Ed Engl ; 63(17): e202320095, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38419359

RESUMO

Ostwald ripening (OR), a classic solution theory describing molecular transfer from metastable crystal to stable one, is applied to design time-dependent crystal hydrogels that can automatically change their mechanical properties. Using a system made from crosslinked polyacrylamide (PAM) and sodium acetate (NaAc), we demonstrate that metastable fibrous crystal networks of NaAc preferably form in PAM hydrogels via a polymer-involving mismatch nucleation. These fibrous crystals would undergo OR and evolve into isolated bulk crystals, leading to a significant reduction in material rigidity (179 folds) and interfacial adhesion (20 folds). This transformation can be applied to program time-dependent self-recovery in shape and self-delamination. Since OR is a ubiquitous, robust feature of various crystals, the approach reported here represents a new direction for designing advanced transient soft materials.

2.
Biosens Bioelectron ; 252: 116130, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38417285

RESUMO

Microfluidic systems find widespread applications in diagnostics, biological research, chemistry, and engineering studies. Among their many critical parameters, flow rate plays a pivotal role in maintaining the functionality of microfluidic systems, including droplet-based microfluidic devices and those used in cell culture. It also significantly influences microfluidic mixing processes. Although various flow rate measurement devices have been developed, the challenge remains in accurately measuring flow rates within customized channels. This paper presents the development of a 3D-printed smartphone-based flow velocity meter. The 3D-printed platform is angled at 30° to achieve transparent flow visualization, and it doesn't require any external optical components such as external lenses and filters. Two LED modules integrated into the platform create a uniform illumination environment for video capture, powered directly by the smartphone. The performance of our platform, combined with a customized video processing algorithm, was assessed in three different channel types: uniform straight channels, straight channels with varying widths, and vessel-like channel patterns to demonstrate its versatility. Our device effectively measured flow velocities from 5.43 mm/s to 24.47 mm/s, with video quality at 1080p resolution and 60 frames per second, for which the measurement range can be extended by adjusting the frame rate. This flow velocity meter can be a useful analytical tool to evaluate and enhance microfluidic channel designs of various lab-on-a-chip applications.


Assuntos
Técnicas Biossensoriais , Técnicas Analíticas Microfluídicas , Dispositivos Ópticos , Smartphone , Microfluídica , Dispositivos Lab-On-A-Chip
3.
Echocardiography ; 41(1): e15747, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284682

RESUMO

OBJECTIVES: Congenital ventricular outpouching (CVO) is a rare cardiac malformation that can manifest as congenital ventricular aneurysm (CVA) and/or congenital ventricular diverticula (CVD). In this study, we describe the prenatal features and postnatal follow-up of 27 cases of CVO. METHODS: The clinical data of 27 patients with CVO who attended Sir Run Run Shaw Hospital Affiliated to the Medical College of Zhejiang University (Zhejiang Province, China) and Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Zhejiang Province, China) from April 2013 to October 2022 were retrospectively analyzed. The patients were also followed up by telephone. The prenatal characteristics and postnatal outcomes of the patients with CVO were evaluated. RESULTS: CVO was detected in 26 cases prenatally, 14 (51.85%) were diagnosed with CVA, nine (33.33%) were diagnosed with CVD, three (11.11%) were equivocal for CVA/CVD, and one (3.70%) was detected with CVA postnatally. Six patients underwent follow-up fetal echocardiography approximately 4 weeks after the initial echocardiography examination, and a significant difference in CVO size was observed between the two examinations (P = .02). Eight patients (29.63%) demonstrated cardiovascular dysfunction, and the median CVO size in fetuses with and without cardiovascular dysfunction was 205 (range: 169-396) mm2 and 124 (range: 92-154.5) mm2 , respectively (P = .01). Correlation was found between CVO size and fetal cardiac dysfunction (p = .000, r = .778). Eight patients (29.63%) had cardiac/extracardiac defects. Thirteen patients were live born, 12 were terminated pregnancies, and two were lost to follow-up. The postpartum size of the CVOs remained stable in six patients, decreased in two patients, dissolved in three patients, and were surgically removed in two patients. With the exception of one patient with CVA complicated with complex congenital cardiac malformation who underwent surgical treatment after birth and who had postoperative left ventricular dysfunction (Case 1), the prognosis of all of the patients was good. CONCLUSION: CVO is often associated with cardiac malformations. The size of prenatal CVOs can increase with gestational development, and cardiovascular dysfunction is significantly related to CVO size. The postpartum prognosis of patients with CVO is good. Echocardiography plays a key role in the diagnosis of congenital ventricular outpouching. Prenatal counseling should be cautious regarding the diagnosis and the prognosis although our cases had a favorable prognosis.


Assuntos
Cardiopatias Congênitas , Ultrassonografia Pré-Natal , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Seguimentos , Cardiopatias Congênitas/diagnóstico por imagem , Feto
4.
Biosens Bioelectron ; 242: 115755, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37839348

RESUMO

Cardiovascular diseases (CVDs) caused by thrombotic events are a significant global health concern, affecting millions of people worldwide. The international normalized ratio (INR) is the most widely used measure of coagulation status, and frequent testing is required to adjust blood-thinning drug dosage, requiring hospital visits and experts to perform the test. Here we present a low-cost and portable smartphone-based device for screening INR levels from whole blood samples at the point of care. Our device uses a 3D printed platform and light-emitting diode backlight modules to create a uniform optical environment, and its foldable design allows for easy transport. Our device also features an algorithm that allows users to acquire and process video of sample flow in a microfluidic channel on their smartphone, providing a cost-effective and convenient option for blood coagulation monitoring at the point of care. We tested the performance of our smartphone-based INR device using both commercially available control samples and clinical human blood samples, demonstrating high accuracy and reliability. Our device has the potential to improve patient outcomes by enabling more frequent monitoring and, as appropriate, dosage adjustments of blood-thinning drugs, providing an affordable and portable option for screening INR levels at the point of care.


Assuntos
Anticoagulantes , Técnicas Biossensoriais , Humanos , Anticoagulantes/farmacologia , Sistemas Automatizados de Assistência Junto ao Leito , Smartphone , Reprodutibilidade dos Testes , Coagulação Sanguínea , Testes Imediatos
5.
ACS Nano ; 17(18): 18148-18163, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37713431

RESUMO

Deficient catalytic sensitivity to the tumor microenvironment is a major obstacle to nanozyme-mediated tumor therapy. Electron transfer is the intrinsic essence for a nanozyme-catalyzed redox reaction. Here, we developed a nanohole-array-induced metallic molybdenum selenide (n-MoSe2) that is enriched with Se vacancies and can serve as an electronic transfer station for cycling electrons between H2O2 decomposition and glutathione (GSH) depletion. In a MoSe2 nanohole array, the metallic phase reaches up to 84.5%, which has been experimentally and theoretically demonstrated to exhibit ultrasensitive H2O2 responses and enhanced peroxidase (POD)-like activities for H2O2 thermodynamic heterolysis. More intriguingly, plenty of delocalized electrons appear due to phase- and vacancy-facilitated band structure reconstruction. Combined with the limited characteristic sizes of nanoholes, the surface plasmon resonance effect can be excited, leading to the broad absorption spectrum spanning of n-MoSe2 from the visible to near-infrared region (NIR) for photothermal conversion. Under NIR laser irradiation, metallic MoSe2 is able to induce out-of-balance redox and metabolism homeostasis in the tumor region, thus significantly improving therapeutic effects. This study that takes advantage of phase and defect engineering offers inspiring insights into the development of high-efficiency photothermal nanozymes.


Assuntos
Peróxido de Hidrogênio , Molibdênio , Transporte de Elétrons , Catálise , Glutationa
6.
Int J Mol Sci ; 24(18)2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37762224

RESUMO

POLD4 plays a crucial part in the complex machinery of DNA replication and repair as a vital component of the DNA polymerase delta complex. In this research, we obtained original information from various publicly available databases. Using a blend of R programming and internet resources, we initiated an extensive examination into the correlation between POLD4 expression and the various elements of cancers. In addition, we performed knockdown experiments in glioma cell lines to authenticate its significant impact. We discovered that POLD4 is upregulated in various malignant tumors, demonstrating a significant correlation with poor patient survival prognosis. Using function analysis, it was uncovered that POLD4 exhibited intricate associations with signaling pathways spanning multiple tumor types. Subsequent investigations unveiled the close association of POLD4 with the immune microenvironment and the effectiveness of immunotherapy. Drugs like trametinib, saracatinib, and dasatinib may be used in patients with high POLD4. Using experimental analysis, we further confirmed the overexpression of POLD4 in gliomas, as well as its correlation with glioma recurrence, proliferation, and the suppressive immune microenvironment. Our research findings indicate that the expression pattern of POLD4 not only serves as a robust indicator of prognosis in cancer patients but also holds promising potential as a new focus for treatment.


Assuntos
DNA Polimerase III , Glioma , Humanos , Linhagem Celular , Proliferação de Células , Replicação do DNA , Glioma/genética , Microambiente Tumoral/genética
7.
BMC Pregnancy Childbirth ; 23(1): 624, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37648962

RESUMO

BACKGROUND: Aneuploidy pregnancy is a severe major birth defect and causes about 50% spontaneous miscarriages with unknown etiology. To date, only a few epidemiological studies with small sample sizes have investigated the risk factors for aneuploidy pregnancy. TP53, MDM2, and miR-34b/c genes are implicated in tumorigenesis with aneuploidy, yet the function of their polymorphisms in aneuploidy pregnancy susceptibility needs to be clarified. OBJECTIVE: To elucidate the association of TP53 rs1042522 G > C, MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C specific polymorphisms with aneuploidy pregnancy. METHODS: In the retrospective case-control study, 330 aneuploidies pregnancy women and 813 normal pregnancy controls were recruited between January 2018 and April 2022 at the First People's Hospital of Yunnan Province, Kunming, China. Three functional polymorphisms, the TP53 rs1042522 G > C (Arg72Pro), MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C, were genotyped using the snapshot method. RESULTS: The frequency distribution of three genotypic variants was not different between case and control pregnant women and was similar to with Hardy-Weinberg Equilibrium (HWE). However, in the younger subgroup (less than 35 years old), a significant difference was detected in allele and recessive model (p = 0.01). In the advanced age subgroup (more than or equal to 35 years old), G of MDM2 rs2279744 T > G revealed a significantly higher frequency in cases than controls (p = 0.045), and miR-34b/c rs4938723 T > C revealed a significant difference under the dominant model (p = 0.03), but no significant differences were observed in other models and in both younger and older subgroup (p > 0.05, respectively). These results suggest that individual polymorphisms were not associated with aneuploidy pregnancy, combined with age, they may serve as a risk factor for aneuploidy pregnancy. CONCLUSION: Combination of TP53 rs1042522 G > C, MDM2 rs2279744 T > G, and miR-34b/c rs4938723 T > C polymorphisms with maternal age may be related to aneuploidy pregnancy susceptibility. These findings might elaborate on the genetic etiology of aneuploidy pregnancy.


Assuntos
Aneuploidia , MicroRNAs , Gravidez , Humanos , Feminino , Adulto , Estudos de Casos e Controles , China , Estudos Retrospectivos , MicroRNAs/genética , Proteína Supressora de Tumor p53/genética , Proteínas Proto-Oncogênicas c-mdm2/genética
9.
BMC Complement Med Ther ; 23(1): 180, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37268931

RESUMO

BACKGROUND: Coronary Artery Disease (CAD) is primarily caused by inflammation which is closely linked to the gut microbiota. Si-Miao-Yong-An (SMYA) decoction is a traditional Chinese herbal formula with anti-inflammatory properties that found to be effective against CAD. However, it is still unclear whether SMYA can modulate gut microbiota and whether it contributes to the improvement of CAD by reducing inflammation and regulating the gut microbiota. METHODS: The identification of components in the SMYA extract was conducted using the HPLC method. A total of four groups of SD rats were orally administered with SMYA for 28 days. The levels of inflammatory biomarkers and myocardial damage biomarkers were measured through ELISA, while echocardiography was used to assess heart function. Histological alterations in the myocardial and colonic tissues were examined following H&E staining. Western blotting was performed to evaluate protein expression, whereas alterations in gut microbiota were determined by 16 s rDNA sequencing. RESULTS: SMYA was found to enhance cardiac function and decrease the expression of serum CK-MB and LDH. SMYA was also observed to inhibit the TLR4/NF-κB signaling pathway by downregulating the protein expression of myocardial TLR4, MyD88, and p-P65, leading to a reduction in serum pro-inflammatory factors. SMYA modified the composition of gut microbiota by decreasing the Firmicutes/Bacteroidetes ratio, modulating Prevotellaceae_Ga6A1 and Prevotellaceae_NK3B3 linked to the LPS/TLR4/NF-κB pathway, and increasing beneficial microbiota such as Bacteroidetes, Alloprevotella, and other bacterial species. Moreover, SMYA was found to safeguard the intestinal mucosal and villi structures, elevate the expression of tight junction protein (ZO-1, occludin), and reduce intestinal permeability and inflammation. CONCLUSIONS: The results indicate that SMYA has the potential to modulate the gut microbiota and protect the intestinal barrier, thereby reducing the translocation of LPS into circulation. SMYA was also found to inhibit the LPS-induced TLR4/NF-κB signaling pathway, leading to a decrease in the release of inflammatory factors, which ultimately mitigated myocardial injury. Hence, SMYA holds promise as a therapeutic agent for the management of CAD.


Assuntos
Microbioma Gastrointestinal , NF-kappa B , Ratos , Animais , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/farmacologia , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais , Inflamação
10.
Ann Med ; 55(1): 2218105, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37318081

RESUMO

BACKGROUND: Si-Miao-Yong-An decoction (SMYAD) is a conventional therapeutic formula for treat thromboangiitis obliterans (TAO), consisting of four Chinese herbs: Lonicerae japonicae Thunb. (Jinyinhua), Scrophularia ningpoensis Hemsl. (Xuanshen), Angelica sinensis (Oliv.) Diels (Danggui) and Glycyrrhiza uralensis Fisch. (Gancao). However, the mechanism of SMYAD in TAO treatment remains unclear. METHODS: Components, as well as potential targets of SMYAD in TAO therapy, were downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Subsequently, with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signalling pathways of the targets enrichment were performed. Next, based on STRING online database, the protein interaction network of vital targets was built and analysed. Molecular docking and calculation of the binding affinity were performed using AutoDock. The PyMOL software was employed to observe docking outcomes of active compounds and protein targets. Based on the predicted outcomes of network pharmacology, in vivo and in vitro tests were performed for validation. In vivo experiment, the TAO rats model was established using sodium laurate injection into the femoral artery. The symptoms as well as pathological changes of the femoral artery were observed. Besides, the predicted targets were verified by the RT-qPCR, in vitro experiment. The cell viability in LPS-induced human umbilical vein endothelial cells (HUVECs) was detected using CCK-8 kit, and the predicted targets were also verified by the RT-qPCR. RESULTS: In the network pharmacology analysis, we obtained 105 chemical components in SMYAD and 24 therapeutic targets. We found that the mechanism SMYAD in TAO therapy was primarily associated with inflammation and angiogenesis by constructing multiple networks. Quercetin, vestitol and beta-sitosterol were important compounds, and interleukin-6 (IL6), MMP9, and VEGFA were key targets. According to molecular docking, active compounds (quercetin, vestitol and beta-sitosterol) and targets (IL6, MMP9 and VEGFA) showed good binding interactions. In in vivo experiment, SMYAD ameliorated the physical signs and pathological changes, inhibited the expression of IL6 and MMP9, and enhanced the expression of VEGFA. In an in vitro experiment, SMYAD increased the cell viability of LPS-induced HUVECs and the expression of VEGFA, and reduced the expression of IL6 and MMP9. CONCLUSIONS: This study showed that SMYAD improves TAO symptoms and inhibits the development of TAO. The mechanism could be associated with anti-inflammatory and therapeutic angiogenesis.


Assuntos
Tromboangiite Obliterante , Humanos , Animais , Ratos , Tromboangiite Obliterante/tratamento farmacológico , Metaloproteinase 9 da Matriz , Farmacologia em Rede , Quercetina , Células Endoteliais , Interleucina-6 , Lipopolissacarídeos , Simulação de Acoplamento Molecular
11.
Natl Sci Rev ; 10(6): nwad056, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37181084

RESUMO

The Zhurong rover of the Tianwen-1 mission landed in southern Utopia Planitia, providing a unique window into the evolutionary history of the Martian lowlands. During its first 110 sols, Zhurong investigated and categorized surface targets into igneous rocks, lithified duricrusts, cemented duricrusts, soils and sands. The lithified duricrusts, analysed by using laser-induced breakdown spectroscopy onboard Zhurong, show elevated water contents and distinct compositions from those of igneous rocks. The cemented duricrusts are likely formed via water vapor-frost cycling at the atmosphere-soil interface, as supported by the local meteorological conditions. Soils and sands contain elevated magnesium and water, attributed to both hydrated magnesium salts and adsorbed water. The compositional and meteorological evidence indicates potential Amazonian brine activities and present-day water vapor cycling at the soil-atmosphere interface. Searching for further clues to water-related activities and determining the water source by Zhurong are critical to constrain the volatile evolution history at the landing site.

12.
Front Genet ; 14: 1105184, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37007941

RESUMO

Background: The genetic etiology of fetal chromosome abnormalities remains unknown, which brings about an enormous burden for patients, families, and society. The spindle assembly checkpoint (SAC) controls the normal procedure of chromosome disjunction and may take part in the process. Objective: The aim of this study was to explore the association between polymorphisms of MAD1L1 rs1801368 and MAD2L1 rs1283639804, involved in SAC and fetal chromosome abnormalities. Methods: The case-control study collected 563 cases and 813 health controls to test the genotypes of MAD1L1 rs1801368 and MAD2L1 rs1283639804 polymorphisms by polymerase chain reaction-restrictive fragment length polymorphism methods (PCR-RFLP). Results: MAD1L1 rs1801368 polymorphism was associated with fetal chromosome abnormalities alone or combined to lower homocysteine (HCY) levels (alone: dominant: OR: 1.75, 95%CI: 1.19-2.57, and p = 0.005; CT vs. CC: OR = 0.73, 95%CI: 0.57-0.94, and p = 0.016; lower HCY: C vs. T: OR = 0.74, 95%CI: 0.57-0.95, and p = 0.02; dominant: OR = 1.75, 95%CI: 0.79-1.92, and p = 0.005). No significant differences were found in other genetic models or subgroups (p > 0.05, respectively). MAD2L1 rs1283639804 polymorphism revealed a sole genotype in the studied population. HCY is significantly associated with fetal chromosome abnormalities in younger groups (OR: 1.78, 95%CI: 1.28-2.47, and p = 0.001). Conclusion: The results implied that the polymorphism of MAD1L1 rs1801368 may become the susceptibility factor to fetal chromosome abnormalities alone or combined to lower HCY levels but not to MAD2L1 rs1283639804 polymorphism. In addition, HCY significantly affects fetal chromosomal abnormalities in younger women.

13.
Am J Transl Res ; 15(1): 612-621, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36777819

RESUMO

OBJECTIVE: To investigate the effect of Xiaoaiping on the general state of rats with malignant ascites secondary to gastric cancer by blocking the transforming growth factor-ß1 (TGF-ß1) signaling pathway. METHODS: Fifty healthy Wistar rats were randomly divided into 5 groups, with 10 rats in each group. After successful modeling, 0.2 g/(20 g∙d), 0.4 g/(20 g∙d) and 0.8 g/(20 g∙d) of Xiaoaiping injections were administrated at the low dose group (LDG), medium dose group (MDG) and high dose group (HDG), respectively. The model group (MG) was injected intraperitoneally with the same amount of sterile normal saline for 8 d. Rats in the control group (CG) were healthy without any treatment. The general states (mental state, dietary habits, reactions and body shape) of rats in each group were observed. The abdominal circumference, platelet (PLT) count, white blood cell (WBC) count, serum ferritin (SF), ascites volume, cell survival rate, and expression levels of TGF-ß1 signaling pathway (TGF-ß1, Smad2) were compared among the groups. RESULTS: PLT and WBC counts in the MG were lower than those in the CG. Ascites volume, tumor cell survival rate, and SF in the MG were higher than those in the LDG, MDG and HDG (P<0.05). Thymus index in the LDG, MDG and HDG were significantly higher than that in the MG (P<0.05). There was no significant difference in the spleen indices among the groups (P>0.05). The kidney index, serum creatinine and urea nitrogen levels in LDG, MDG and HDG were significantly lower than those of MG (P<0.05). The LDG, MDG and HDG exhibited significantly higher peripheral blood CD4+ cells and CD4+/CD8+, and lower CD8+ level, as compared with the MG (P<0.05). The levels of serum interferon γ (IFN-γ), interleukin (IL)-1α, IL-1ß, IL-2, IL-4 and tumor necrosis factor-α (TNF-α) in the LDG, MDG and HDG were higher than those in the MG (P<0.05). The ascites volume and tumor cell survival rate were decreased sequentially in the LDG, MDG and HDG (P<0.05). The MG had higher mRNA levels of TGF-ß1 and Smad2 than the CG (P<0.05). No statistically significant difference was found in TGF-ß1 and Smad2 between the LDG and MG (P>0.05). CONCLUSION: Xiaoaiping could significantly reduce the ascites volume in rats with gastric cancer, inhibit the production of tumor cells in the abdominal cavity, and improve the general state of rats in a dose-dependent manner. The mechanism may be related to the down-regulation of the mRNA level of TGF-ß1 and Smad2.

14.
J Membr Biol ; 256(1): 25-34, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36040494

RESUMO

Exosomes are special extracellular vesicles secreted by cells, which are of great significance in the basic research of life science and clinical application and has become a hot research field with rapid development in recent 10 years. Therefore, the isolation and separation of exosomes is particularly important for the research and application of exosomes. This paper aims to review the research progress of exosome isolation and separation methods in recent years, including ultracentrifugation, ultrafiltration, size­exclusion chromatography, precipitation, immunomagnetic bead capture method, aptamer-based isolation, and isolation methods based on microfluidic technology. It is generally accepted that most of the existing methods have limitations, for example, ultracentrifugation is time-consuming and laborious, and immunomagnetic bead capture method and aptamer-based separation method have small sample processing capacity and high cost. As a result, we also introduce some common situations in which two or more methods are combined for use. Finally, the separation and isolation methods including all those presented in this review were compared and summarized.


Assuntos
Exossomos , Vesículas Extracelulares , Exossomos/química , Exossomos/metabolismo , Ultracentrifugação/métodos , Transporte Biológico
15.
J Cell Mol Med ; 27(2): 277-286, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36578229

RESUMO

RNF7 has been reported to play critical roles in various cancers. However, the underlying mechanisms of RNF7 in glioma development remain largely unknown. Herein, the expression level of RNF7 was examined in tissues by quantitative real-time PCR, Western blotting and immunohistochemistry. The effect of RNF7 on glioma progression was measured by performing CCK-8 and apoptosis assays, cell cycle-related experiments and animal experiments. The effect of RNF7 on PI3K/AKT signalling pathway was tested by Western blotting. First, we found that RNF7 was upregulated in tumour tissue compared with normal brain tissue, especially in high-grade glioma, and the high expression of RNF7 was significantly related to tumour size, Karnofsky Performance Scale score and a poor prognosis. Second, RNF7 overexpression facilitated tumour cell cycle progression and cell proliferation and suppressed apoptosis. Conversely, RNF7 knockdown suppressed tumour cell cycle progression and cell proliferation and facilitated apoptosis. Furthermore, follow-up mechanistic studies indicated that RNF7 could facilitate glioma cell proliferation and cell cycle progression and inhibit apoptosis by activating the PI3K/AKT signalling pathway. This study shows that RNF7 can clearly promote glioma cell proliferation by facilitating cell cycle progression and inhibiting apoptosis by activating the PI3K/AKT signalling pathway. Targeting the RNF7/PI3K/AKT axis may provide a new perspective on the prevention or treatment of glioma.


Assuntos
Glioma , Proteínas Proto-Oncogênicas c-akt , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/metabolismo
16.
Front Pharmacol ; 13: 1024292, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36483736

RESUMO

HJ11 is a novel traditional Chinese medicine developed from the appropriate addition and reduction of Si-Miao-Yong-An decoction, which has been commonly used to treat ischemia-reperfusion (I/R) injury in the clinical setting. However, the mechanism of action of HJ11 components remains unclear. Ferroptosis is a critical factor that promotes myocardial I/R injury, and the pathophysiological ferroptosis-mediated lipid peroxidation causes I/R injury. Therefore, this study explored whether HJ11 decoction ameliorates myocardial I/R injury by attenuating ACSL4-mediated ferroptosis. This study also explored the effect of ACSL4 expression on iron-dependent programmed cell death by preparing a rat model of myocardial I/R injury and oxygen glucose deprivation/reperfusion (OGD/R)-induced H9c2 cells. The results showed that HJ11 decoction improved cardiac function; attenuated I/R injury, apoptosis, oxidative stress, mitochondrial damage, and iron accumulation; and reduced infarct size in the myocardial I/R injury rat model. Additionally, HJ11 decoction suppressed the expression of ferroptosis-promoting proteins [Acyl-CoA synthetase long-chain family member 4 (ACSL4) and cyclooxygenase-2 (COX2)] but promoted the expression of ferroptosis-inhibiting proteins [ferritin heavy chain 1 (FTH1) and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4)] in the myocardial tissues of the I/R injury rat model. Similar results were found with the OGD/R-induced H9c2 cells. Interestingly, ACSL4 knockdown attenuated iron accumulation, oxidative stress, and ferroptosis in the OGD/R-treated H9c2 cells. However, ACSL4 overexpression counteracted the inhibitory effect of the HJ11 decoction on OGD/R-triggered oxidative stress and ferroptosis in H9c2 cells. These findings suggest that HJ11 decoction restrained the development of myocardial I/R injury by regulating ACSL4-mediated ferroptosis. Thus, HJ11 decoction may be an effective medication to treat myocardial I/R injury.

17.
Lab Chip ; 22(24): 4758-4773, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36398687

RESUMO

Bacterial infections have long been a serious global health issue. Biofilm formation complicates matters even more. The biofilm's extracellular polymeric substances (EPSs) matrix protects bacteria from the host's immune responses, yielding strong adhesion and drug resistance as the biofilm matures. Early bacterial biofilm detection and bacterial biofilm growth monitoring are crucial to treating biofilm-associated infections. Current detection methods are highly sensitive but not portable, are time-consuming, and require expensive equipment and complex operating procedures, limiting their use at the point of care. Therefore, there is an urgent need to develop affordable, on-body, and non-invasive biomedical sensors to continuously monitor and detect early biofilm growth at the point of care through personalized telemedicine. Herein, recent advances in developing non-invasive biomedical sensors for early detection and monitoring bacterial biofilm growth are comprehensively reviewed. First, biofilm's life cycle and its impact on the human body, such as biofilm-associated disease and infected medical devices, are introduced together with the challenges of biofilm treatment. Then, the current methods used in clinical and laboratory settings for biofilm detection and their challenges are discussed. Next, the current state of non-invasive sensors for direct and indirect detection of bacterial biofilms are summarized and highlighted with the detection parameters and their design details. Finally, commercially available products, challenges of current devices, and the further trend in biofilm detection sensors are discussed.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Humanos
18.
Sensors (Basel) ; 22(19)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36236593

RESUMO

Conventional point cloud simplification algorithms have problems including nonuniform simplification, a deficient reflection of point cloud characteristics, unreasonable weight distribution, and high computational complexity. A simplification algorithm, namely, the multi-index weighting simplification algorithm (MIWSA), is proposed in this paper. First, the point cloud is organized with a bounding box and kd-trees to find the neighborhood of each point, and the points are divided into small segments. Second, the feature index of each point is calculated to indicate the characteristics of the points. Third, the analytic hierarchy process (AHP) and criteria importance through intercriteria correlation (CRITIC) are applied to weight these indexes to determine whether each point is a feature point. Fourth, non-feature points are judged as saved or abandoned according to their spatial relationship with the feature points. To verify the effect of the MIWSA, 3D model scanning datasets are calculated and analyzed, as well as field area scanning datasets. The accuracy for the 3D model scanning datasets is assessed by the surface area and patch numbers of the encapsulated surfaces, and that for field area scanning datasets is evaluated by the DEM error statistics. Compared with existing algorithms, the overall accuracy of the MIWSA is 5% to 15% better. Additionally, the running time is shorter than most. The experimental results illustrate that the MIWSA can simplify point clouds more precisely and uniformly.

19.
Org Biomol Chem ; 20(43): 8461-8464, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36254875

RESUMO

A facile synthetic protocol for the preparation of spiro diheterocycles from easily available 2'-aminoacetophenones, isocyanates and 1,4-benzoquinones or quinone monoimines under mild conditions has been developed. This multi-component transformation is characterized by efficient construction of two heterocycles and one valuable quaternary carbon in one pot via an in situ cyclization-respiroannulation strategy. Moreover, this reaction showed a broad substrate scope, and generated diverse five-membered oxaspiros.


Assuntos
Isocianatos , Estrutura Molecular , Ciclização
20.
Comput Math Methods Med ; 2022: 7102736, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158120

RESUMO

This study is aimed at screening prognostic biomarkers in cholangiocarcinoma (CHOL) based on competitive endogenous RNA (ceRNA) regulatory network analysis. Microarray data for lncRNAs, mRNA, and miRNAs were downloaded from the GEO and TCGA databases. Differentially expressed RNAs (DERs) were identified in CHOL and normal liver tissue samples. WGCNA was used to identify disease-related gene modules. By integrating the information from the starBase and DIANA-LncBasev2 databases, we constructed a ceRNA network. Survival analysis was performed, and a prognostic gene-based prognostic score (PS) model was generated. The correlation between gene expression and immune cell infiltration or immune-related feature genes was analyzed using TIMER. Finally, real-time quantitative PCR (RT-qPCR) was used to verify the expression of the 10 DERs with independent prognosis. A large cohort of DERs was identified in the CHOL and control samples. The ceRNA network consisted of 6 lncRNAs, 2 miRNAs, 90 mRNAs, and 98 nodes. Ten genes were identified as prognosis-related genes, and a ten-gene signature PS model was constructed, which exhibited a good prognosis predictive ability for risk assessment of CHOL patients (AUC value = 0.975). Four genes, ELF4, AGXT, ABCG2, and LDHD, were associated with immune cell infiltration and closely correlated with immune-related feature genes (CD14, CD163, CD33, etc.) in CHOL. Additionally, the consistency rate of the RT-qPCR results and bioinformatics analysis was 80%, implying a relatively high reliability of the bioinformatic analysis results. Our findings suggest that the ten-signature gene PS model has significant prognostic predictive value for patients with CHOL. These four immune-related DERs are involved in the progression of CHOL and may be useful prognostic biomarkers for CHOLs.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , RNA Longo não Codificante , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores , Biomarcadores Tumorais/genética , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes
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