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The oncofetal mRNA-binding protein IGF2BP1 belongs to a conserved family of RNA-binding proteins. It primarily promotes RNA stability, regulates translation and RNA localization, and mediates gene expression through its downstream effectors. Numerous studies have demonstrated that IGF2BP1 plays crucial roles in embryogenesis and carcinogenesis. IGF2BP1-modulated cell proliferation, invasion, and chemo-resistance in solid tumors have attracted researchers' attention. Additionally, several studies have highlighted the importance of IGF2BP1 in hematologic malignancies and hematological genetic diseases, positioning it as a promising therapeutic target for hematological disorders. However, there is a lack of systematic summaries regarding the IGF2BP1 gene within the hematological field. In this review, we provide a comprehensive overview of the discovery and molecular structure of IGF2BP1, along with recent studies on its role in regulating embryogenesis. We also focus on the mechanisms by which IGF2BP1 regulates hematological malignancies through its interactions with its targeted mRNAs. Furthermore, we systematically elucidate the function and mechanism of IGF2BP1 in promoting fetal hemoglobin expression in adult hematopoietic stem/progenitor cells. Finally, we discuss the limitations and challenges of IGF2BP1 as a therapeutic target, offering insights into its prospects.
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Doenças Hematológicas , Proteínas de Ligação a RNA , Humanos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Doenças Hematológicas/genética , Doenças Hematológicas/metabolismo , Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Suscetibilidade a Doenças , Peptídeos Semelhantes à InsulinaRESUMO
While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients, effective treatments are still lacking. Here, we identified homeobox C10 (HOXC10) as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis. Through RNA-seq approach and patient tissue studies, we demonstrated that HOXC10 expression was dramatically increased. Genetic depletion of HOXC10 preferentially impeded cell proliferation and migration in vitro. The bioluminescence imaging and micro-CT results demonstrated that inhibition of HOXC10 significantly reduced bone metastasis of KRAS-mutant lung cancer in vivo. Mechanistically, the transcription factor HOXC10 activated NOD1/ERK signaling pathway to reprogram epithelial-mesenchymal transition (EMT) and bone microenvironment by activating the NOD1 promoter. Strikingly, inhibition of HOXC10 in combination with STAT3 inhibitor was effective against KRAS-mutant lung cancer bone metastasis by triggering ferroptosis. Taken together, these findings reveal that HOXC10 effectively alleviates pan-KRAS-mutant lung cancer with bone metastasis in the NOD1/ERK axis-dependent manner, and support further development of an effective combinatorial strategy for this kind of disease.
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Neoplasias Ósseas , Proteínas de Homeodomínio , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Animais , Feminino , Humanos , Camundongos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Osteólise/genética , Osteólise/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD1/metabolismoRESUMO
Diabetic bone defects, exacerbated by hyperglycemia-induced inflammation and oxidative stress, present significant therapeutic challenges. This study introduces a novel injectable scaffold, MgH2@PLGA/F-GM, consisting of foamed gelatin-methacryloyl (GelMA) and magnesium hydride (MgH2) microspheres encapsulated in poly(lactic-co-glycolic acid) (PLGA). This scaffold is uniquely suited for diabetic bone defects, conforming to complex shapes and fostering an environment conducive to tissue regeneration. As it degrades, Mg(OH)2 is released and dissolved by PLGA's acidic byproducts, releasing therapeutic Mg2+ ions. These ions are instrumental in macrophage phenotype modulation, inflammation reduction, and angiogenesis promotion, all vital for diabetic bone healing. Additionally, hydrogen (H2) released during degradation mitigates oxidative stress by diminishing reactive oxygen species (ROS). This multifaceted approach not only reduces ROS and inflammation but also enhances M2 macrophage polarization and cell migration, culminating in improved angiogenesis and bone repair. This scaffold presents an innovative strategy for addressing the complexities of diabetic bone defect treatment.
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Gelatina , Hidrogéis , Hidrogênio , Magnésio , Gelatina/química , Magnésio/química , Hidrogênio/química , Hidrogênio/farmacologia , Hidrogênio/uso terapêutico , Hidrogênio/administração & dosagem , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Regeneração Óssea/efeitos dos fármacos , Metacrilatos/química , Preparações de Ação Retardada/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Alicerces Teciduais/química , Espécies Reativas de Oxigênio/metabolismo , Células RAW 264.7 , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacosRESUMO
Herbicides (HBCs) are extensively used in modern agriculture. However, their potential negative impacts on environmental media have emerged as a significant environmental concern. In this study, we employed positive matrix factorization (PMF) to identify the potential sources of HBCs. Furthermore, we utilized a multi-matrix ecological risk model to assess the risks associated with HBCs in both surface water and groundwater in the black soil region of Northeast China. The findings revealed that the levels of ∑15HBCs in surface water and groundwater ranged from 585.84 to 6466.96 ng/L and 4.80 to 11,774.64 ng/L, respectively. The PMF results indicated that surface runoff and erosion accounted for 50% of the total HBCs in water, serving as the primary sources. All tested HBCs exhibited acute risk values within acceptable levels. The risk index for the ∑15HBCs was categorized as "moderate risk" in 31% of the surface waters and 13% of the groundwaters. However, 4% of the groundwater sampling sites reached the "high risk" level. The chronic risk quotient of ∑15HBCs in surface water and groundwater was 92% and 62% at the "high risk" level, respectively. Interestingly, non-carcinogenic HBCs contributed more significantly to the ecotoxicology of the aquatic system than carcinogenic HBCs. This study provides comprehensive information on the legacy of HBCs in water bodies and emphasizes the potential risks posed by HBCs to aquatic systems. The results obtained from this study could help relevant management authorities in developing and implementing effective regulations to mitigate the ecological and environmental risks associated with HBCs.
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Monitoramento Ambiental , Água Subterrânea , Herbicidas , Poluentes Químicos da Água , China , Medição de Risco , Herbicidas/análise , Herbicidas/toxicidade , Poluentes Químicos da Água/análise , Água Subterrânea/química , CidadesRESUMO
Intercellular communication can be mediated by direct cell-to-cell contact and indirect interactions through secretion of soluble chemokines, cytokines, and growth factors. Extracellular vesicles (EVs) have emerged as important mediators of cell-to-cell and cell-to-environment communications. EVs from tumor cells, immune cells, and stromal cells can remodel the tumor microenvironment and promote cancer cell survival, proliferation, metastasis, immune evasion, and therapeutic resistance. Most importantly, EVs as natural nanoparticles can be manipulated to serve as a potent delivery system for targeted cancer therapy. EVs can be engineered or modified to improve their ability to target tumors and deliver therapeutic substances, such as chemotherapeutic drugs, nucleic acids, and proteins, for the treatment of cancer. This review provides an overview of the biogenesis and recycling of EVs, discusses their roles in cancer development, and highlights their potential as a delivery system for targeted cancer therapy.
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The main purpose of this review was to examine the evidence of the relationship between active smoking or passive smoking during pregnancy and atopic dermatitis in offspring. The protocol was written following the PRISMA Checklist and was registered in the PROSPERO database (registration number CRD42022381136). We implemented a comprehensive search in PubMed, Embase and Web of Science databases to identify all potentially related articles from inception through 1 December 2022. We assessed cohort studies and case-control studies using the Newcastle-Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of cross-sectional studies. Heterogeneity was investigated by using Cochrane Q tests and I2 statistics. In addition, according to the research design, population source and population size, the reasons for the heterogeneity were analysed. A total of 15 observational studies were included in this analysis. Our meta-analysis suggests that atopic dermatitis in offspring is not associated with active smoking during pregnancy (pooled OR, 0.96 [95% CI 0.86-1.07]); however, it is related to passive smoking (OR, 1.52 [95% CI 1.36-1.70]). Passive smoking during pregnancy is associated with an increased risk of eczema development in offspring. More research is needed to explore the risk of active smoking and eczema development in offspring, especially the association between measurements of pregnancy cotinine levels in maternal body fluids and AD in offspring.
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Dermatite Atópica , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Poluição por Fumaça de Tabaco , Feminino , Humanos , Gravidez , Dermatite Atópica/etiologia , Exposição Materna/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
Coal mining carries inherent risks of catastrophic gas explosions capable of inflicting severe lung injury. Using complementary in vivo and in vitro models, we explored mechanisms underlying alveolar epithelial damage and repair following a gas explosion in this study. In a rat model, the gas explosion was demonstrated to trigger inflammation and injury within the alveolar epithelium. The following scRNA-sequencing revealed that alveolar epithelial cells exhibited the most profound transcriptomic changes after gas explosion compared to other pulmonary cell types. In the L2 alveolar epithelial cells, the blast was found to cause autophagic flux by inducing autophagosome formation, LC3 lipidation, and p62 degradation. Transcriptomic profiling of the L2 cells identified PI3K-Akt and p53 pathways as critical modulators governing autophagic and oxidative stress responses to blast damage. Notably, Thrombospondin-1 (Thbs1) was determined for the first time as a pivotal node interconnecting these two pathways. The findings of this study illuminate intricate mechanisms of alveolar epithelial injury and recovery after blast trauma, highlighting autophagic and oxidative stress responses mediated by Thbs1-associated PI3K-Akt and p53 pathways as high-value therapeutic targets, and strategic modulation of these pathways in future studies may mitigate lung damage by reducing oxidative stress while engaging endogenous tissue repair processes like autophagy.
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Lesão Pulmonar , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Estresse Oxidativo , Autofagia , Trombospondinas/metabolismoRESUMO
Gas explosions (GE) are a prevalent and widespread cause of traumatic brain injury (TBI) in coal miners. However, the impact and mechanism of curcumin on GE-induced TBI in rats remain unclear. In this study, we simulated GE-induced TBI in rats and administered curcumin orally at a dose of 100 mg/kg every other day for 7 days to modulate the gut microbiota in TBI rats. We employed 16S rRNA sequencing and LC-MS/MS metabolomic analysis to investigate changes in the intestinal flora and its metabolic profile. Additionally, we utilized ELISA, protein assays, and immunohistochemistry to assess neuroinflammatory signaling molecules for validation. In a rat TBI model, GE resulted in weight loss, pathological abnormalities, and cortical hemorrhage. Treatment with curcumin significantly mitigated histological abnormalities and microscopic mitochondrial structural changes in brain tissue. Furthermore, curcumin treatment markedly ameliorated GE-induced brain dysfunction by reducing the levels of several neuroinflammatory signaling molecules, including neuron-specific enolase, interleukin (IL)-1ß, IL-6, and cryptothermic protein 3. Notably, curcumin reshaped the gut microbiome by enhancing evenness, richness, and composition. Prevotella_9, Alloprevotella, Bacilli, Lactobacillales, Proteobacteria, and Gammaproteobacteria were identified as prominent members of the gut microbiota, increasing the linear discriminant analysis scores and specifically enhancing the abundance of bacteria involved in the nuclear factor (NF)-κB signaling pathway, such as Lachnospiraceae and Roseburia. Additionally, there were substantial alterations in serum metabolites associated with metabolic NF-κB signaling pathways in the model group. Curcumin administration reduced serum lipopolysaccharide levels and downregulated downstream Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/NF-κB signaling. Furthermore, curcumin alleviated GE-induced TBI in rats by modulating the gut microbiota and its metabolites. Based on these protective effects, curcumin may exert its influence on the gut microbiota and the TLR4/MyD88/NF-κB signaling pathways to ameliorate GE-induced TBI.
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Lesões Encefálicas Traumáticas , Curcumina , Microbioma Gastrointestinal , Ratos , Animais , NF-kappa B/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Lipopolissacarídeos , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Cromatografia Líquida , Explosões , RNA Ribossômico 16S , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/patologiaRESUMO
Chicken primordial germ cells (PGCs) are important cells with significant implications in preserving genetic resources, chicken breeding and production, and basic research on genetics and development. Currently, chicken PGCs can be cultured long-term in vitro to produce single-cell clones. However, systematic exploration of the cellular characteristics of these single-cell clonal lines has yet to be conducted. In this study, single-cell clonal lines were established from male and female PGCs of Rugao Yellow Chicken and Shouguang Black Chicken, respectively, using a micropipette-based method for single-cell isolation and culture. Analysis of glycogen granule staining, mRNA expression of pluripotency marker genes (POUV, SOX2, NANOG), germ cell marker genes (DAZL, CVH), and SSEA-1, EMA-1, SOX2, C-KIT, and CVH protein expression showed positive results, indicating that PGCs maintain normal cellular properties after single-cell cloning. Furthermore, tests on proliferation ability and gene expression levels in PGC single-cell clonal lines showed high expression of the pluripotency-related genes and TERT compared to control PGCs, and PGC single-cell clonal lines demonstrated higher proliferation ability. Finally, green fluorescent protein (GFP)-PGC single-cell clonal lines were established, and it was found that these single-cell clonal lines could still migrate into the gonads of recipients, suggesting their potential for germ-line transmission. This study systematically validated the normal cellular characteristics of PGC single-cell clonal lines, indicating that they could be applied in genetic modification research on chickens.
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Galinhas , Células Germinativas , Animais , Masculino , Feminino , Galinhas/genética , Linhagem Celular , Células Cultivadas , Células Germinativas/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismoRESUMO
BACKGROUND: Accurate prediction of response to neoadjuvant chemoradiotherapy (nCRT) is very important for treatment plan decision in locally advanced rectal cancer (LARC). The aim of this study was to investigate whether self-attention mechanism based multi-sequence fusion strategy applied to multiparametric magnetic resonance imaging (MRI) based deep learning or hand-crafted radiomics model construction can improve prediction of response to nCRT in LARC. METHODS: This retrospective analysis enrolled 422 consecutive patients with LARC who received nCRT before surgery at two hospitals. All patients underwent multiparametric MRI scans with three imaging sequences. Tumor regression grade (TRG) was used to assess the response of nCRT based on the resected specimen. Patients were separated into 2 groups: poor responders (TRG 2, 3) versus good responders (TRG 0, 1). A self-attention mechanism, namely channel attention, was applied to fuse the three sequence information for deep learning and radiomics models construction. For comparison, other two models without channel attention were also constructed. All models were developed in the same hospital and validated in the other hospital. RESULTS: The deep learning model with channel attention mechanism achieved area under the curves (AUCs) of 0.898 in the internal validation cohort and 0.873 in the external validation cohort, which was the best performed model in all cohorts. More importantly, both the deep learning and radiomics model that applied channel attention mechanism performed better than those without channel attention mechanism. CONCLUSIONS: The self-attention mechanism based multi-sequence fusion strategy can improve prediction of response to nCRT in LARC.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias Retais , Humanos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Estudos Retrospectivos , Terapia Neoadjuvante/métodos , Resultado do Tratamento , Quimiorradioterapia/métodosRESUMO
Herein, a novel magneto-mediated electrochemical aptasensor using the signal amplification technologies of DNAzyme motor and electrocatalyst for vanilla (VAN) detection was fabricated. The D/B duplex, formed by the DNAzyme motor that was each silenced by a blocker, and hairpin DNA1 (H1) containing adenosine ribonucleotide (rA) site were tethered on the sites of the gold nanoparticles@hollow porphyrinic-Metal-organic framework/polyethyleneimine-reduced graphene oxide (AuHPCN-222/PEI-rGO)-modified gold electrode (AuE). Then, after homogeneous and specific recognition in the presence of the VAN, trigger DNA was released and enriched by magnetic separation technique and introduced to the sensing platform to activate the DNAzyme motor, which efficiently improved target recognition capability and avoided the obstacle of multiple DNA strands tangling. More interestingly, the activated DNAzyme motor could repeatedly bind to and cleave H1 in the presence of Mg2+, leading to the exposure of a plethora of capture probes. The thionine (Thi) functionalized hairpin DNA2 (H2)-Pt@Ni-Co as signal probes could hybridize with capture probes. Additionally, the Pt@Ni-Co electrocatalysts presented catalytic activity towards Thi to obtain stronger electrochemical signals. VAN with concentrations ranging from 1 × 10-6 to 10 µM was determined and a detection limit was down to 0.15 pM. The designed electrochemical sensor was highly selective with specificity, stability, reproducibility, and reliable capability for monitoring the VAN in real samples.
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Técnicas Biossensoriais , DNA Catalítico , Nanopartículas Metálicas , Vanilla , Ouro , Reprodutibilidade dos Testes , Técnicas Biossensoriais/métodos , Limite de Detecção , DNA , Técnicas Eletroquímicas/métodosRESUMO
Bone fractures have always been a burden to patients due to their common occurrence and severe complications. Traditionally, operative treatments have been widely used in the clinic for implanting, despite the fact that they can only achieve bone fixation with limited stability and pose no effect on promoting tissue growth. In addition, the nondegradable implants usually need a secondary surgery for implant removal, otherwise they may block the regeneration of bones resulting in bone nonunion. To overcome the low degradability of implants and avoid multiple surgeries, tissue engineers have investigated various biodegradable materials for bone regeneration, whereas the significance of stability of long-term bone fixation tends to be neglected during this process. Combining the traditional orthopedic implantation surgeries and emerging tissue engineering, we believe that both bone fixation and bone regeneration are indispensable factors for a successful bone repair. Herein, we define such a novel idea as bone regenerative fixation (BRF), which should be the main future development trend of biodegradable materials.
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Abdominal adhesions, a commonly observed complication of abdominal surgery, have a high incidence and adversely affect patients' physical and mental health. The primary causes of abdominal adhesions are intraoperative trauma, acute inflammatory response, bleeding, and foreign body infection. Because most current treatment approaches for abdominal adhesions are limited, improved and novel postoperative anti-adhesion regimens are urgently needed. In this study, we developed calcium polyphenol network (CaPN) microspheres based on the self-assembly of the natural triphenolic compound gallic acid and Ca2+ in solution. The physicochemical properties of CaPNs, including their hemostatic, antibacterial, antioxidant, and anti-inflammatory activities, were investigated in vitro. Bleeding and cecal-abdominal wall adhesion models were established to observe the hemostatic activity of CaPNs and their preventive effect on postoperative abdominal wall adhesion in vivo. The results showed that CaPNs significantly reduced inflammation, oxidative stress, fibrosis, and abdominal adhesion formation and had good hemostatic and antibacterial properties. Our findings suggest a novel strategy for the prevention of postoperative adhesions.
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Cálcio , Hemostáticos , Humanos , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Aderências Teciduais/prevenção & controle , Antibacterianos/farmacologiaRESUMO
Osteoporosis is a systemic skeletal disease characterized by low bone mass and degradation of bone tissue microarchitecture, leading to enhanced bone fragility and increased fracture risk. However, the pathogenesis of osteoporosis is unclear. Our results showed that BMSCs dervied from ovariectomized rats had a higher capacity for osteogenesis and lipogenic differentiation compared to the control group. In the meantime, we identified a total of 205 differentially expressed proteins and 2294 differentially expressed genes in BMSCs isolated from ovariectomized rats by proteomics analysis and transcriptome sequencing, respectively. These differentially expressed proteins and genes were mainly involved in ECM-receptor interaction signaling pathway. We speculate that BMSCs derived from ovariectomized rats have a higher potential for bone formation because expression of ECM collagen or genes encoding collagen in the bone ECM in BMSCs isolated from ovariectomized rats are increased compared with that from control group, which provided the prerequisite for the increased bone turnover effect. To conclusion, our results may provid new ideas for further research on the pathogenesis of osteoporosis.
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Células-Tronco Mesenquimais , Osteoporose , Ratos , Animais , Multiômica , Proliferação de Células , Osteoporose/genética , Diferenciação Celular , Osteogênese , Células-Tronco Mesenquimais/metabolismo , Células CultivadasRESUMO
ABSTRACT: Blast lung injuries (BLIs) are frequent because of industrial accidents and terrorist groups. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs (BMSCs-Exo) have become a hot topic in modern biology because of their significance in damage healing, immune regulation, and gene therapy. The aim of this study is to investigate the effect of BMSCs and BMSCs-Exo on BLI in rats caused by gas explosion. Here, BMSCs and BMSCs-Exo were transplanted into BLI rats via tail vein and then evaluated pathological alterations, oxidative stress, apoptosis, autophagy, and pyroptosis in the lung tissue. Through histopathology and changes in malondialdehyde (MDA) and superoxide dismutase (SOD) contents, we discovered that oxidative stress and inflammatory infiltration in the lungs were significantly reduced by BMSCs and BMSCs-Exo. After treatment with BMSCs and BMSCs-Exo, apoptosis-related proteins, such as cleaved caspase-3 and Bax, were significantly decreased, and the ratio of Bcl-2/Bax was significantly increased; the level of pyroptosis-associated proteins, including NLRP3, GSDMD-N, cleaved caspase-1, IL-1ß, and IL-18, were decreased; autophagy-related proteins, beclin-1 and LC3, were downregulated while P62 was upregulated; the number of autophagosomes was decreased. In summary, BMSCs and BMSCs-Exo attenuate BLI caused by gas explosion, which may be associated with apoptosis, aberrant autophagy, and pyroptosis.
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Exossomos , Lesão Pulmonar , Células-Tronco Mesenquimais , Humanos , Lesão Pulmonar/metabolismo , Proteína X Associada a bcl-2/metabolismo , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , ApoptoseRESUMO
Osteoarthritis (OA) is a chronic osteoarthropathy characterized by the progressive degeneration of articular cartilage and synovial inflammation. Early OA clinical treatments involve intra-articular injection of glucocorticoids, oral acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), which are used for anti-inflammation and pain relief. However, long-term use of these agents will lead to inevitable side effects, even aggravate cartilage loss. At present, there are no disease-modifying OA drugs (DMOADs) yet approved by regulatory agencies. Polarization regulation of synovial macrophages is a new target for OA treatment. Inhibiting M1 polarization and promoting M2 polarization of synovial macrophages can alleviate synovial inflammation, relieve joint pain and inhibit articular cartilage degradation, which is a promising strategy for OA treatment. In this study, we describe the molecular mechanisms of macrophage polarization and its key role in the development of OA. Subsequently, we summarize the latest progress of strategies for OA treatment through macrophage reprogramming, including small molecule compounds (conventional western medicine and synthetic compounds, monomer compounds of traditional Chinese medicine), biomacromolecules, metal/metal oxides, cells, and cell derivatives, and interprets the molecular mechanisms, hoping to provide some information for DMOADs development.
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Cartilagem Articular , Osteoartrite , Humanos , Osteoartrite/tratamento farmacológico , Inflamação , Macrófagos , Acetaminofen/uso terapêuticoRESUMO
Circular RNA (circRNAs) is a covalently closed circular non-coding RNA formed by reverse back-splicing from precursor messenger RNA. It is found widely in eukaryotic cells and can be released to the surrounding environment and captured by other cell types. This, circRNAs serve as connections between different cell types for the mediation of multiple signaling pathways. CircRNAs reshape the tumor microenvironment (TME), a key factor involved in all stages of cancer development, by regulating epithelial-stromal transformation, tumor vascularization, immune cell function, and inflammatory responses. Immune cells are the most abundant cellular TME components, and they have profound toxicity to cancer cells. This review summarizes circRNA regulation of immune cells, including T cells, natural killer cells, and macrophages; highlights the impact of circRNAs on tumor progression, treatment, and prognosis; and indicates new targets for tumor immunotherapy.
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Neoplasias , RNA Circular , Humanos , RNA Circular/genética , RNA/genética , Microambiente Tumoral/genética , RNA Mensageiro/genética , Neoplasias/genética , Precursores de RNARESUMO
Circulating tumor cells (CTCs) are cancer cells that are released from the original tumor and circulate in the blood vessels, carrying greatly similar constituents as the original tumor. Therefore, CTCs have a significant value in cancer prognosis, early diagnosis, and anti-cancer therapy. However, their rarity and heterogeneity make the isolation of CTCs an arduous task. In the present research, we propose a double spiral chip-embedded micro-trapezoid filter (SMT filter) for the sensitive isolation of the CTCs of prostate cancer by spectral detection. SMT filters were elongated to effectively capture CTCs and this distinctive design was conducive to their isolation and enrichment. The SMT filters were verified with tumor cells and artificial patient blood with a capture efficiency as high as 94% at a flow rate of 1.5 mL h-1. As a further validation, the SMT filters were validated in isolating CTCs from 10 prostate cancers and other cancers in 4 mL blood samples. Also, the CTCs tested positive for each patient blood sample, ranging from 83-114 CTCs. Significantly, we advanced hyperspectral imaging to detect the characteristic spectrum of CTCs both captured in situ on SMT filters and enriched after isolation. The CTCs could be positively identified by hyperspectral imaging with complete integrity of the cell morphology and an improved characteristic spectrum. This represents a breakthrough in the conventional surface-enhanced Raman scattering (SERS) spectroscopy of nanoparticles. Also, the characteristic spectrum of the CTCs would be highly beneficial for distinguishing the cancer type and accurate for enumerating tumor cells with varied intensities. Furthermore, a novel integrated flower-shaped microfilter was presented with all these aforementioned merits. The success of both the SMT filters and characteristic spectral detection indicated their feasibility for further clinical analysis, the evaluation of cancer therapy, and for potential application.
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A novel ultrasensitive electrochemical aptasensor was proposed for quantitative detection of Cd2+. To this end, flower-like polyethyleneimine-functionalized molybdenum disulfide-supported gold nanoparticles (PEI-MoS2 NFs@Au NPs) were used as substrates for the modification of bare gold electrodes (AuE). PEI-MoS2 NFs@Au NPs not only possessed excellent biocompatibility and large specific surface area to enhance the cDNA loading capacity, but also possessed good conductivity to accelerate the electron transfer rate. Furthermore, the preparation of dendritic platinum-palladium nanoparticles (PtPd NPs) can effectively load Cd2+-aptamer. Thionine and aptamers were loaded onto PtPd NPs to construct Thi-PtPd NPs-aptamer signal probes. The signal probes were captured by the cDNA immobilized on the electrode via base-pairing rule, and the signal of Thi was detected by differential pulse voltammetry (DPV). In the presence of Cd2+, aptamer-cDNA unwinded, and the combination of aptamer and Cd2+ caused the signal probes to fall off the electrode and the electrical signal decreases. Under optimal conditions, the proposed aptasensor exhibited a linear relationship between the logarithm of Cd2+ concentration and the current response over a wide range of 1 × 10-3 nM to 1 × 102 nM, with a detection limit of 2.34 × 10-4 nM. At the same time, the aptasensor was used to detect Cd2+ in tap water with satisfactory results. In addition, it has good reproducibility, selectivity and stability, and has broad application prospects in heavy metal analysis.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Nanocompostos , Platina , Ouro , Cádmio , Paládio , Molibdênio , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Polietilenoimina , DNA Complementar , Reprodutibilidade dos Testes , Água , Limite de DetecçãoRESUMO
Developing rapid detection technology for adenosine triphosphate (ATP) is crucial in quality supervision and food safety. Herein, an electrochemical aptasensor based on an aptazyme-catalyzed signal amplification strategy is constructed for ATP detection using polyethyleneimine-functionalized molybdenum disulfide (PEI-MoS2)/Au@PtPd nanobipyramids (MoS2/Au@PtPd NBPs) as a modification material. Additionally, a novel kind of nitrogen-rich covalent organic framework (COF) is prepared using melamine and cyanuric acid (MCA). We synthesize MCA and the Co-based metal organic framework (Co-MOF) as the signal label. Due to the fact that π-π stacking interactions of Co-MOF@MCA can expand the load efficiency and surface concentration of the signal label, the signal response is an order of magnitude higher than that of Co-MOF or MCA as the signal label. Target ATP changes the conformation of the aptazyme, and it becomes activated. With the assistance of metal ions, the signal label is circularly cleaved, causing an amplification of the signal. Among them, MoS2/Au@PtPd NBPs have a large specific surface area and good electrical conductivity and can carry substantial DNA strands and amplify the redox signal of methylene blue (MB). Under optimal conditions, the aptasensor can detect ATP from 10 pM to 100 µM with a low limit of detection of 7.37 × 10-10 µM. Therefore, the novel aptasensor has extensive application prospects in quality supervision and food safety.