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1.
ACS Omega ; 9(18): 20410-20424, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38737081

RESUMO

The droplet-to-iron electrochemical reaction is common in nature and industrial production, and it causes damage to the economy, safety, and the environment. The electrochemical reaction of droplet-to-iron is a coupling process of wetting and corrosion. Presently, investigations into electrochemical reactions mainly focus on the corrosions caused by a solution, and wetting is rarely considered. However, for the droplet-to-iron electrochemical reaction, the mechanism of charge transfer in the process is still unclear. In this paper, a reactive molecular dynamics simulation model for the droplet-to-iron electrochemical reaction is developed for the first time. The electrochemical reaction of droplet-to-iron is studied, and the interaction between droplet wetting and corrosion on iron is investigated. The effects of temperature, electric field strength, and salt concentration on the electrochemical reaction are explored. Results show that droplet wetting on the iron surface and the formation of a single-molecular-layer ordered structure are prerequisites for corrosion. The hydroxyl radicals that penetrate the ordered structure acquire electrons from iron atoms on the substrate surface under the action of Coulomb forces and form iron-containing oxides with these iron atoms. The corrosion products and craters lead to a reduced droplet height, which promotes droplet wetting on iron and further intensifies the droplet-to-iron electrochemical reaction.

3.
Cancer Cell Int ; 24(1): 163, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725047

RESUMO

It is commonly assumed that gastrointestinal cancer is the most common form of cancer across the globe and is the leading contributor to cancer-related death. The intricate mechanisms underlying the growth of GI cancers have been identified. It is worth mentioning that both non-coding RNAs (ncRNAs) and certain types of RNA, such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), can have considerable impact on the development of gastrointestinal (GI) cancers. As a tumour suppressor, in the group of short non-coding regulatory RNAs is miR-34a. miR-34a silences multiple proto-oncogenes at the post-transcriptional stage by targeting them, which inhibits all physiologically relevant cell proliferation pathways. However, it has been discovered that deregulation of miR-34a plays important roles in the growth of tumors and the development of cancer, including invasion, metastasis, and the tumor-associated epithelial-mesenchymal transition (EMT). Further understanding of miR-34a's molecular pathways in cancer is also necessary for the development of precise diagnoses and effective treatments. We outlined the most recent research on miR-34a functions in GI cancers in this review. Additionally, we emphasize the significance of exosomal miR-34 in gastrointestinal cancers.

5.
Front Cell Infect Microbiol ; 14: 1230650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638824

RESUMO

Objective: To evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests. Methods: Patients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms. Results: Thirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/42) based on pathogen diagnosis. Conclusion: Both platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection.


Assuntos
Sequenciamento por Nanoporos , Infecções Respiratórias , Humanos , Estudos Retrospectivos , China , Infecções Respiratórias/diagnóstico , Antibacterianos , Líquido da Lavagem Broncoalveolar , Metagenômica , Sequenciamento de Nucleotídeos em Larga Escala , Sensibilidade e Especificidade
6.
Cancer Cell Int ; 24(1): 146, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654238

RESUMO

BACKGROUND: Colon cancer ranks third among global tumours and second in cancer-related mortality, prompting an urgent need to explore new therapeutic targets. C6orf15 is a novel gene that has been reported only in Sjogren's syndrome and systemic lupus erythematosus patients. We found a close correlation between increased C6orf15 expression and the occurrence of colon cancer. The aim of this study was to explore the potential of C6orf15 as a therapeutic target for colorectal cancer. METHOD: RNA-seq differential expression analysis of the TCGA database was performed using the R package 'limma.' The correlation between target genes and survival as well as tumour analysis was analysed using GEPIA. Western blot and PCR were used to assess C6orf15 expression in colorectal cancer tissue samples. Immunofluorescence and immunohistochemistry were used to assess C6orf15 subcellular localization and tissue expression. The role of C6orf15 in liver metastasis progression was investigated via a mouse spleen infection liver metastasis model. The association of C6orf15 with signalling pathways was assessed using the GSEA-Hallmark database. Immunohistochemistry (IHC), qPCR and western blotting were performed to assess the expression of related mRNAs or proteins. Biological characteristics were evaluated through cell migration assays, MTT assays, and Seahorse XF96 analysis to monitor fatty acid metabolism. RESULTS: C6orf15 was significantly associated with liver metastasis and survival in CRC patients as determined by the bioinformatic analysis and further verified by immunohistochemistry (IHC), qPCR and western blot results. The upregulation of C6orf15 expression in CRC cells can promote the nuclear translocation of ß-catenin and cause an increase in downstream transcription. This leads to changes in the epithelial-mesenchymal transition (EMT) and alterations in fatty acid metabolism, which together promote liver metastasis of CRC. CONCLUSION: Our study identified C6orf15 as a marker of liver metastasis in CRC. C6orf15 can activate the WNT/ß-catenin signalling pathway to promote EMT and fatty acid metabolism in CRC.

7.
Cancer Cell Int ; 24(1): 90, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429738

RESUMO

BACKGROUND: Patients with colorectal cancer (CRC) with liver metastasis or drug resistance have a poor prognosis. Previous research has demonstrated that PPP2R1B inactivation results in the development of CRC. However, the role of PPP2R1B in CRC metastasis and drug resistance is unclear. METHODS: Venny 2.1 was used to determine the intersection between survival-related differentially expressed genes (DEGs) and liver metastasis-related DEGs according to RNA-seq data from The Cancer Genome Atlas (TCGA) and the GEO database (GSE179979). LC‒MS/MS and coimmunoprecipitation were performed to predict and verify the substrate protein of PPP2R1B. Gene Set Variation Analysis (GSVA) was subsequently utilized to assess pathway enrichment levels. The predictive performance of PPP2R1B was assessed by regression analysis, Kaplan-Meier (KM) survival analysis and drug sensitivity analysis. Immunohistochemistry (IHC), qRT-PCR and western blotting were performed to measure the expression levels of related mRNAs or proteins. Biological features were evaluated by wound healing, cell migration and invasion assays and CCK-8 assays. A mouse spleen infection liver metastasis model was generated to confirm the role of PPP2R1B in the progression of liver metastasis in vivo. RESULTS: According to bioinformatics analysis, PPP2R1B is significantly associated with liver metastasis and survival in CRC patients, and these findings were further verified via immunohistochemistry (IHC), qPCR and Western blotting. Pathway enrichment and LC‒MS/MS analysis revealed that PPP2R1B is negatively associated with the MAPK/ERK signalling pathway. Additionally, PD98059, a MAPK/ERK pathway inhibitor, inhibited EMT in vitro by reversing the changes in key proteins involved in EMT signalling (ZEB1, E-cadherin and Snail) and ERK/MAPK signalling (p-ERK) mediated by PPP2R1B. Oxaliplatin sensitivity prediction and validation revealed that PPP2R1B silencing decreased Oxaliplatin chemosensitivity, and these effects were reversed by PD98059 treatment. Moreover, PPP2R1B was coimmunoprecipitated with p-ERK in vitro. A negative correlation between PPP2R1B and p-ERK expression was also observed in clinical CRC samples, and the low PPP2R1B/high p-ERK coexpression pattern indicated a poor prognosis in CRC patients. In vivo, PPP2R1B silencing significantly promoted liver metastasis. CONCLUSIONS: This study revealed that PPP2R1B induces dephosphorylation of the p-ERK protein, inhibits liver metastasis and increases Oxaliplatin sensitivity in CRC patients and could be a potential candidate for therapeutic application in CRC.

8.
Int J Pharm X ; 7: 100238, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38511068

RESUMO

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

9.
Orthod Craniofac Res ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512245

RESUMO

OBJECTIVE: To investigate the effects of congenital unilateral first permanent molar occlusal loss (CUMOL) on the morphology and position of temporomandibular joint (TMJ). MATERIALS AND METHODS: Cone-beam computed tomography (CBCT) images of 37 patients with CUMOL (18 males and 19 females, mean age: 13.60 ± 4.38 years) were divided into two subgroups according to the status of second molar (G1: the second molar not erupted, n = 18, G2: second molar erupted, n = 19). The control group consisted of 33 normal occlusion patients (9 males and 24 females, mean age: 16.15 ± 5.44 years) and was divided into 2 subgroups accordingly (G3: the second molar had not erupted, n = 18, G4: the second molar had erupted and made contact with the opposing tooth, n = 15). Linear and angular measurements were used to determine the characteristics of TMJ. RESULTS: In G1, the condyle on the side of the CUMOL shifts posteriorly, with significant side differences observed in Anterior space (AS, P < .05) and Posterior space (PS, P < .05). However, with the eruption of the second permanent molars, in G2, the condyle on the CUMOL side moves posteriorly and inferiorly. This results in significant lateral differences in the AS (P < .05), PS (P < .05), and Superior space (SS, P < .05). Additionally, there is an increase in the thickness of the roof of the glenoid fossa (TRF) on the CUMOL side (P < .05), and a decrease in the inclination of the bilateral articular eminences (P < .05). CONCLUSIONS: CUMOL can affect the position and the morphology of the condyle and was associated with the eruption of the second permanent molars. Before the eruption of the second permanent molars, CUMOL primarily affects the position of the condyle. After the emergence of the second permanent molars, CUMOL leads to changes in both the condyle's position and the morphology of the glenoid fossa.

10.
Arch Microbiol ; 206(2): 63, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217700

RESUMO

During the investigations of macrofungi resources in Zhejiang Province, China, an interesting wood rot fungus was collected. Based on morphological and molecular phylogenetic studies, it is described as a new species, Anthracophyllum sinense. A. sinense is characterized by its sessile, charcoal black and pleurotoid pileus, sparse lamellae occasionally branching, clavate basidia with long sterigmata [(3-)6-7(-8) µm], and non-heteromorphous cystidia. A. sinense establishes a separate lineage close to A. archeri and A. lateritium in the phylogenetic tree.


Assuntos
Agaricales , Basidiomycota , Filogenia , DNA Fúngico/genética , China
11.
Environ Sci Pollut Res Int ; 31(7): 11178-11191, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38217805

RESUMO

As logistics carbon emission efficiency is an essential industry linking regions, investigating this issue from a spatial correlation perspective is practically significant. Utilizing data from 282 prefecture-level cities spanning 2006 to 2019, we used a super slacks-based measure model, a modified gravity model, motif analysis, the Infomap algorithm, and an exponential random graph model to analyze the spatial correlation patterns and influencing factors of logistics carbon emission efficiency. The following conclusions were drawn. (1) The spatial correlation of logistics carbon emission efficiency during the study period exhibited a core-edge pattern, with the central region emerging as a high-correlation hub. (2) The scale of the spatial association network community of carbon emission efficiency in the logistics industry changed constantly, and the stability of the network community structure gradually increased. From a microstructural perspective, the dispersed-mode structure was a pivotal element in the formation of the spatial correlation network of logistics carbon emission efficiency. (3) Node interaction tendencies were a critical force driving network formation. Financial investment, government concern, international openness, population density, and innovation ability were conducive to the formation of spatial correlations of logistics carbon emission efficiency.


Assuntos
Algoritmos , Carbono , China , Cidades , Governo , Desenvolvimento Econômico
12.
J Therm Biol ; 119: 103752, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38194751

RESUMO

Heat stress can lead to hormonal imbalances, weakened immune system, increased metabolic pressure on the liver, and ultimately higher animal mortality rates. This not only seriously impairs the welfare status of animals, but also causes significant economic losses to the livestock industry. Due to its rich residual bioactive components and good safety characteristics, traditional Chinese medicine (TCM) residue is expected to become a high-quality feed additive with anti-oxidative stress alleviating function. This study focuses on the potential of Shengxuebao mixture herbal residue (SXBR) as an anti-heat stress feed additive. Through the UPLC (ultra performance liquid chromatography) technology, the average residue rate of main active ingredients from SXBR were found to be 25.39%. SXBR were then added into the basal diet of heat stressed New Zealand rabbits at the rates of 5% (SXBRl), 10% (SXBRm) and 20% (SXBRh). Heat stress significantly decreased the weight gain, as well as increased neck and ear temperature, drip loss in meat, inflammation and oxidative stress. Also, the hormone levels were disrupted, with a significant increase in serum levels of CA, COR and INS. After the consumption of SXBR in the basal diet for 3 weeks, the weight of New Zealand rabbits increased significantly, and the SXBRh group restored the redness value of the meat to a similar level as the control group. Furthermore, the serum levels T3 thyroid hormone in the SXBRh group and T4 thyroid hormone in the SXBRm group increased significantly, the SXBRh group showed a significant restoration in inflammation markers (IL-1ß, IL-6, and TNF-α) and oxidative stress markers (total antioxidant capacity, HSP-70, MDA, and ROS) levels. Moreover, the real-time fluorescence quantitative PCR analysis found that, the expression levels of antioxidant genes such as Nrf2, HO-1, NQO1, and GPX1 were significantly upregulated in the SXBRh group, and the expression level of the Keap1 gene was significantly downregulated. Additionally, the SXBRm group showed significant upregulation in the expression levels of HO-1 and NQO1 genes. Western blot experiments further confirmed the up-regulation of Nrf2, Ho-1 and NQO1 proteins. This study provides a strategy for the utilization of SXBR and is of great significance for the green recycling of the TCM residues, improving the development of animal husbandry and animal welfare.


Assuntos
Antioxidantes , Transtornos de Estresse por Calor , Coelhos , Animais , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Estresse Oxidativo , Resposta ao Choque Térmico , Inflamação , Transtornos de Estresse por Calor/veterinária
13.
J Stomatol Oral Maxillofac Surg ; 125(1): 101632, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37703917

RESUMO

BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) is a non-invasive physical stimulation application for the therapy of articular cartilage injury. This study aimed to explore the therapeutic effects of low-intensity pulsed ultrasound in treating masticatory myositis and synovitis in temporomandibular joint disorders and to establish an evaluation system to evaluate the clinical efficacy. METHODS: TMD patients who met the inclusion criteria in the temporomandibular joint clinic of the affiliated Stomatological Hospital of Chongqing Medical University from April 3, 2021, to December 2021 were selected. Before the start and after 7 days of LIPUS treatment, the Fricton temporomandibular joint disorder index, Visual Analog Scale (VAS), and Pressure Difference of Precision Manometer (PD) were measured. A paired t-test was used to compare the values of the Fricton index, VAS, and PD before and after treatment in each group. One-way ANOVA analysis of variance was used to compare the differences between groups. RESULTS: After one week of LIPUS treatment, the PI, DI and CMI of the Fricton index in the masticatory myositis (PI: P < 0.001; CMI: P < 0.001; DI: P = 0.2641, ns) and the synovitis group (DI: P < 0.001; CMI: P < 0.001, PI: P = 0.9729, ns) significantly decreased. The VAS of the masticatory myositis group and the synovitis group were significantly reduced (P < 0.001). The PD between the affected and healthy sides of the masticatory myositis group and the synovitis group was significantly reduced (P < 0.001), and the reduction was more evident in the M group. CONCLUSIONS: LIPUS is effective in pain relief in patients with masticatory myositis and joint synovitis, meanwhile, masticatory myositis was more sensitive to LIPUS. A new comprehensive clinical efficacy evaluation system which includes PV, FI, and VAS was created to better 2 diagnose masticatory myositis and joint synovitis.


Assuntos
Sinovite , Transtornos da Articulação Temporomandibular , Humanos , Sinovite/diagnóstico por imagem , Sinovite/terapia , Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/terapia , Resultado do Tratamento , Ondas Ultrassônicas
14.
Adv Mater ; 36(5): e2307420, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37697624

RESUMO

Chiral B/N embedded multi-resonance (MR) emitters open a new paradigm of circularly polarized (CP) organic light-emitting diodes (OLEDs) owing to their unique narrowband spectra. However, pure-red CP-MR emitters and devices remain exclusive in literature. Herein, by introducing a B-N covalent bond to lower the electron-withdrawing ability of the para-positioned B-π-B motif, the first pair of pure-red double hetero-[n]helicenes (n = 6 and 7) CP-MR emitter peaking 617 nm with a small full-width at half-maximum of 38 nm and a high photoluminescence quantum yield of ≈100% in toluene is developed. The intense mirror-image CP light produced by the enantiomers is characterized by high photoluminescence dissymmetry factors (gPL ) of +1.40/-1.41 × 10-3 from their stable helicenes configuration. The corresponding devices using these enantiomers afford impressive CP electroluminescence dissymmetry factors (gEL ) of +1.91/-1.77 × 10-3 , maximum external quantum efficiencies of 36.6%/34.4% and Commission Internationale de I'Éclairage coordinates of (0.67, 0.33), exactly satisfying the red-color requirement specified by National Television Standards Committee (NTSC) standard. Notably a remarkable long LT95 (operational time to 95% of the initial luminance) of ≈400 h at an initial brightness of 10,000 cd m-2 is also observed for the same device, representing the most stable CP-OLED up to date.

15.
Neural Netw ; 169: 733-743, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37979499

RESUMO

This paper is concerned with non-fragile output-feedback control for time-delay neural networks with persistent dwell time (PDT) switching in a continuous-time setting. The main purpose is to design an output-feedback controller subject to gain fluctuations, guaranteeing both asymptotic stability and L2-gain of the closed-loop control system. To achieve reduced conservatism, the controller is formulated to depend not only on the system mode but also on a time scheduler constructed based on the PDT switching rule and minimum time span. A criterion for the asymptotic stability and L2-gain analysis is established through the application of the Gronwall-Bellman inequality and mathematical induction. Then, a numerically tractable design approach for the desired controller is proposed, utilizing a four-section piecewise time-dependent Lyapunov-Krasovskii functional and several nonlinearity decoupling techniques. For comparative purposes, a simple case, independent of the time scheduler, is also investigated, and the corresponding controller design approach is presented. Finally, a simulation example is given to illustrate the effectiveness and superiority of the proposed system mode and time scheduler dual-dependent controller design approach.


Assuntos
Algoritmos , Redes Neurais de Computação , Retroalimentação , Simulação por Computador , Tempo
16.
Orthod Craniofac Res ; 27(2): 287-296, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37929647

RESUMO

OBJECTIVE: To compare the prevalence of fenestration and dehiscence between pre- and post-orthodontic treatment and to explore the factors related to fenestration and dehiscence in the anterior teeth after treatment. METHODS: This study included 1000 cone-beam computed tomography (CBCT) scans of 500 patients before (T1) and after (T2) orthodontic treatment. These images were imported into Dolphin 11.9 software to detect alveolar fenestration and dehiscence in the anterior teeth area. The chi-square test and Fisher's exact test were performed to compare the prevalence of alveolar bone defects between time points T1 and T2. A total of 499 patients were selected for logistic regression analysis to examine the correlation among age, sex, crowding, sagittal facial type, extraction, miniscrew use and fenestration or dehiscence post-treatment. RESULTS: Except for the maxillary lingual fenestration and labial fenestration of mandibular canines, a significant change in the prevalence of fenestration and dehiscence was noted between time points T1 and T2 (P < .025). Multinomial logistic regression showed that age, miniscrew use and extraction highly influenced the prevalence of anterior lingual dehiscence (P < .05). Dehiscence of the mandibular labial side (skeletal Class III vs. I, OR = 2.368, P = .000) and fenestration of the mandibular lingual side (skeletal Class II vs. I, OR = 2.344, P = .044) were strongly correlated with the sagittal facial type. Dehiscence of the maxillary labial side (moderate vs. mild, OR = 1.468, P = .017) was significantly associated with crowding. CONCLUSIONS: Older age, maxillary moderate crowding, skeletal Class III, extraction and miniscrew potentially significantly affect the prevalence of anterior teeth dehiscence. Adult females, skeletal Class III patients on the mandibular labial side and skeletal Class II patients on the mandibular lingual side should be monitored for anterior teeth fenestration.


Assuntos
Incisivo , Má Oclusão , Adulto , Feminino , Humanos , Estudos Retrospectivos , Má Oclusão/diagnóstico por imagem , Má Oclusão/epidemiologia , Má Oclusão/terapia , Mandíbula , Tomografia Computadorizada de Feixe Cônico , Maxila , Análise Multivariada
17.
JCI Insight ; 9(3)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38127456

RESUMO

Despite clinical use of immunosuppressive agents, the immunopathogenesis of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remains unclear. Src homology 3-binding protein 2 (SH3BP2), a scaffold protein, forms an immune signaling complex (signalosome) with 17 other proteins, including phospholipase Cγ2 (PLCγ2) and Rho-guanine nucleotide exchange factor VAV2 (VAV2). Bioinformatic analysis of human glomerular transcriptome (Nephrotic Syndrome Study Network cohort) revealed upregulated SH3BP2 in MCD and FSGS. The SH3BP2 signalosome score and downstream MyD88, TRIF, and NFATc1 were significantly upregulated in MCD and FSGS. Immune pathway activation scores for Toll-like receptors, cytokine-cytokine receptor, and NOD-like receptors were increased in FSGS. Lower SH3BP2 signalosome score was associated with MCD, higher estimated glomerular filtration rate, and remission. Further work using Sh3bp2KI/KI transgenic mice with a gain-in-function mutation showed ~6-fold and ~25-fold increases in albuminuria at 4 and 12 weeks, respectively. Decreased serum albumin and unchanged serum creatinine were observed at 12 weeks. Sh3bp2KI/KI kidney morphology appeared normal except for increased mesangial cellularity and patchy foot process fusion without electron-dense deposits. SH3BP2 co-immunoprecipitated with PLCγ2 and VAV2 in human podocytes, underscoring the importance of SH3BP2 in immune activation. SH3BP2 and its binding partners may determine the immune activation pathways resulting in podocyte injury leading to loss of the glomerular filtration barrier.


Assuntos
Glomerulosclerose Segmentar e Focal , Nefrose Lipoide , Síndrome Nefrótica , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/metabolismo , Rim/patologia , Glomérulos Renais/patologia , Camundongos Transgênicos , Nefrose Lipoide/patologia , Síndrome Nefrótica/metabolismo , Fosfolipase C gama/genética , Fosfolipase C gama/metabolismo
18.
Proc Natl Acad Sci U S A ; 120(51): e2304213120, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38085773

RESUMO

The disequilibrium of amyloid ß-peptide (Aß) between the central and peripheral pools has been claimed as an initiating event in Alzheimer's disease (AD). In this study, we employ discoidal high-density lipoproteins (HDL-Disc) mimicking Aß antibody for directional flux of Aß from central to peripheral catabolism, with desirable safety and translation potential. Structurally, HDL-Disc assembly (polyDisc) is prepared with aid of chitosan derivative polymerization. After intranasal administration and response to slightly acidic nasal microenvironment, polyDisc depolymerizes into carrier-free HDL-Disc with chitosan derivatives that adhere to the mucosal layer to reversibly open tight junctions, helping HDL-Disc penetrate the olfactory pathway into brain. Thereafter, HDL-Disc captures Aß into microglia for central clearance or ferries Aß out of the brain for liver-mediated compensatory catabolism. For synergy therapy, intranasal administration of polyDisc can effectively reduce intracerebral Aß burden by 97.3% and vascular Aß burden by 73.5%, ameliorate neurologic damage, and rescue memory deficits in APPswe/PS1dE9 transgenic AD mice with improved safety, especially vascular safety. Collectively, this design provides a proof of concept for developing Aß antibody mimics to mobilize a synergy of central and peripheral Aß clearance for AD treatment.


Assuntos
Doença de Alzheimer , Quitosana , Camundongos , Animais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Quitosana/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Camundongos Transgênicos , Modelos Animais de Doenças
19.
Cell Mol Biol (Noisy-le-grand) ; 69(12): 118-123, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38063108

RESUMO

Thyroid cancer (TC) originates from thyroid epithelial cells and is one of the common malignant tumors in the endocrine system. The aim of our study was to explore the dynamic changes of serum miR-105-3p expression after TC surgery and its correlation with clinicopathological manifestations, and evaluate its clinical value as a potential biomarker after surgery. A total of 100 TC patients were selected as the research objects. To detect serum miR-105-3p in patients and its correlation with tumor pathological characteristics and the dynamic changes of postoperative serum miR-105-3p in patients to evaluate its prognostic value as a potential biomarker. Serum miR-105-3p increases in patients with well-differentiated TC and lymph node metastasis; Serum miR-105-3p gradually decreases after surgery, and there is a significant difference between 4 days after surgery and before surgery,  serum miR-105-3p level can significantly distinguish between patients with poor prognosis and good prognosis within 2 years after the operation, and it can predict the improvement of the prognosis of TC after surgery. The level of serum miR-105-3p is closely related to tumor differentiation and lymph node metastasis in TC patients. Its level gradually decreases with the passage of time after surgery. It has a good diagnostic value for the prognosis of TC after surgery and is expected to become a TC surgery. Potential biomarkers for post-diagnosis.


Assuntos
MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , Metástase Linfática , Prognóstico , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Biomarcadores , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica
20.
Onco Targets Ther ; 16: 1027-1042, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107762

RESUMO

Purpose: Colon cancer is one of the leading causes of death worldwide, and screening of effective molecular markers for the diagnosis is prioritised for prevention and treatment. This study aimed to investigate the diagnostic and predictive potential of genes related to the lipid metabolism pathway, regulated by a protein called sterol-regulatory element-binding transcription Factor 2 (SREBF2), for colon cancer and patient outcomes. Methods: We used machine-learning algorithms to identify key genes associated with SREBF2 in colon cancer based on a public database. A nomogram was created to assess the diagnostic value of these genes and validated in the Cancer Genome Atlas. We also analysed the relationship between these genes and the immune microenvironment of colon tumours, as well as the correlation between gene expression and clinicopathological characteristics and prognosis in the China Medical University (CMU) clinical cohort. Results: Three genes, 7-dehydrocholesterol reductase (DHCR7), hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2), and Ral guanine nucleotide dissociation stimulator-like 1 (RGL1), were identified as hub genes related to SREBF2 and colon cancer. Using the TCGA dataset, receiver operating characteristic curve analysis showed the area under the curve values of 0.943, 0.976, and 0.868 for DHCR7, HSD11B2, and RGL1, respectively. In the CMU cohort, SREBF2 and DHCR7 expression levels were correlated with TNM stage and tumour invasion depth (P < 0.05), and high DHCR7 expression was related to poor prognosis of colon cancer (P < 0.05). Furthermore, DHCR7 gene expression was positively correlated with the abundance of M0 and M1 macrophages and inversely correlated with the abundance of M2 macrophages, suggesting that the immune microenvironment may play a role in colon cancer surveillance. There was a correlation between SREBF2 and DHCR7 expression across cancers in the TCGA database. Conclusion: This study highlights the potential of DHCR7 as a diagnostic marker and therapeutic target for colon cancer.

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