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Osteoarthritis (OA) is a degenerative whole-joint disease in which the synovium and joint cartilage become inflamed and damaged. The essential role of inflammation in the development of OA has been recognized recently. Accordingly, simultaneous regulation of local inflammation and tissue degeneration is proposed as a promising therapeutic strategy. Herein, multifunctional biomimetic apoptotic nanovesicles (Apo-NVs) are constructed with plasma membrane derived from apoptotic T cells. The anti-inflammatory microRNA-124 is further encapsulated into Apo-NVs in the hope of achieving an enhanced immunomodulatory effect. It is found that apoptotic nanovesicles, including Apo-NVs and Apo-NVs-miR-124, both efficiently promote the M2 repolarization of M1 macrophages and inhibit the degenerative phenotype of chondrocytes. Further in vivo studies show that Apo-NVs and Apo-NVs-miR-124 alleviate synovial inflammation and protect cartilage tissue from degeneration in OA mice. The study highlights the potential of Apo-NVs in treating OA and other inflammation-related diseases.
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Mitochondrial network architecture, which is closely related to mitochondrial function, is mechanically sensitive and regulated by multiple stimuli. However, the effects of microtopographic cues on mitochondria remain poorly defined. Herein, polycaprolactone (PCL) surfaces were used as models to investigate how micropatterns regulate mitochondrial network architecture and function in rat adipose-derived stem cells (rASCs). It was found that large pit (LP)-induced rASCs to form larger and more complex mitochondrial networks. Consistently, the expression of key genes related to mitochondrial dynamics revealed that mitochondrial fusion (MFN1 and MFN2) and midzone fission (DRP1 and MFF) were increased in rASCs on LP. In contrast, the middle pit (MP)-enhanced mitochondrial biogenesis, as evidenced by the larger mitochondrial area and higher expression of PGC-1. Both LP and MP promoted ATP production in rASCs. It is likely that LP increased ATP levels through modulating mitochondrial network architecture while MP stimulated mitochondria biogenesis to do so. Our study clarified the regulation of micropatterned surfaces on mitochondria, highlighting the potential of LP and MP as a simple platform to stimulate mitochondria and the subsequent cellular function of MSCs.
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BACKGROUND: Schizophrenia, bipolar disorder and major depression have been reported to be associated with some cancers. However, the magnitude of the causal relationship between them remains unclear. This study aims to explore the potential association between three major mental diseases and the risk of some cancers. METHODS: We performed the two-sample Mendelian randomization(MR) analysis using publicly available genome-wide association studies (GWAS) statistics to investigate the causal relationship between these three mental diseases and some common types of cancers, including breast cancer, ovarian cancer, lung cancer, colorectal cancer, bladder cancer, prostate cancer, thyroid cancer, pancreatic cancer, malignant melanoma and glioma. We obtained genetic association estimates for schizophrenia, bipolar disorder and depression from the Psychiatric Genomics Consortium.The genetic association estimates for cancers were obtained from the UK Biobank, the MRC-IEU consortium and the GliomaScan consortium. RESULTS: After correction for heterogeneity and horizontal pleiotropy, we detected suggestive evidence for the association between thyroid cancer and genetically predicted schizophrenia (OR = 1.543, 95% CI: 1.023-2.328, P = 0.039), and thyroid cancer and major depression (OR = 3.573, 95% CI: 1.068-11.953, P = 0.039). No evidence of causal effects of schizophrenia, major depression and bipolar disorder on other types of cancers. CONCLUSIONS: Our findings suggest the association of schizophrenia and major depression and the development of thyroid cancer.
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Transtorno Bipolar , Transtorno Depressivo Maior , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neoplasias , Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/epidemiologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/epidemiologia , Transtorno Bipolar/genética , Transtorno Bipolar/epidemiologia , Neoplasias/genética , Predisposição Genética para Doença , Feminino , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: Pituitary abscess (PA) accounts for only 0.3-0.5% of sellar masses, and the lack of specific clinical symptoms makes diagnosing PA difficult without a surgical biopsy. In clinical practice, PA is often mistaken for cystic pituitary adenoma, craniopharyngioma, and Rathke's cyst. Thus, this study aims to investigate challenges in diagnosing PA and evaluate the importance of combining intraoperative surgery with postoperative antibiotic treatment. METHODS: We conducted a retrospective analysis of 19 patients diagnosed with PA through histopathology. All patients underwent transsphenoidal surgery (TSS) for pituitary adenomas after undergoing comprehensive preoperative evaluations, including routine tests, endocrine assay, and imaging examination. Furthermore, we compared different treatments for pituitary abscess (PA) to determine the most effective approach for achieving a favorable prognosis. RESULTS: The most prevalent symptom of PA was headache, especially in the frontal-temporal and vertex regions, ranging from mild to moderate severity. Hypopituitarism-related symptoms were also frequently observed, including hypaphrodisia, cold sensitivity, fatigue, weight loss, polyuria, and amenorrhea. Twelve patients exhibited abnormalities in endocrinology examinations. Diagnosing PA correctly is challenging. In our study, none of the patients were correctly diagnosed with PA prior to surgery, and many sellar lesions were misdiagnosed. The favorable prognosis was largely attributed to surgical intervention and active postoperative antibiotic therapy. CONCLUSIONS: Given the lack of clarity in preoperative diagnosis, typical intraoperative findings and effective antibiotics treatment are more indicative of the correct diagnosis than other tests. In terms of therapy, optimal surgical intervention and active postoperative antibiotic treatment contribute to resolving the challenges posed by PA.
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Doenças da Hipófise , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/cirurgia , Doenças da Hipófise/terapia , Idoso , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/terapia , Neoplasias Hipofisárias/patologia , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/terapia , Abscesso/diagnóstico , Abscesso/terapia , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: Colorectal adenoma represents the critical step in the development of colorectal cancer. The establishment of an immortalized epithelial cell line of colorectal adenoma of human origin would provide a tool for studying the mechanism of precancerous lesions, screening the efficacy of novel drugs, and constructing in vivo disease models. Currently, there is no commercially available stable supply of epithelial cells from precancerous lesions. AIMS: This study aimed to establish a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection. METHODS: Simian vacuolating virus 40(SV40), SV40-LT overexpressed lentivirus vector, was transfected into primary human colorectal adenomatous polyp epithelial cells. The transfected cells were screened, and the screened cells were amplified to obtain the epithelial cell line: IHCRA- CELL. The cells were identified by morphological observation, cell proliferation, Quantitative real-time PCR (qPCR), and Short Tandem Repeats (STR) experiments. Morphologically, the cells showed epithelial-like characteristics, such as polygon shape, desmosomes mitochondria, and strong positive keratin staining. There was no significant difference between the transfected cells and the primary cells. Through the STR identification experiment, no matching cell lines were found in the cell lines retrieval. CONCLUSION: We successfully established a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection, which has been patented and is now preserved in the Chinese Typical Culture Preservation Center. It was verified that the transformed cells maintained the phenotype and biological characteristics of epithelial cells. This cell line can be used to study the mechanism of precancerous lesions, screen the efficacy of novel drugs, and construct in vivo disease models.
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Herein, a magnetic bead-based chemiluminescence assay is reported to detect type IV collagen (col-IV) in serum samples. Magnetic beads (MBs) exhibit biocompatibility. Taking advantage of this property, they were conjugated with the col-IV antibody. For the determination of col-IV, the interaction of the col-IV sample, anti-(col-IV)-alkaline phosphatase (anti-(col-IV)-ALP) and anti-col-IV-magnetic beads (anti-(col-IV)-MBs) was performed to generate chemiluminescence. Under the optimized conditions, the developed method displayed good linearity in the concentration range of 20-2000 ng mL-1 with the limit of 0.79 ng mL-1. The repeatability coefficient of variation (CV) for col-IV detection ranged from 3.16% to 7.50%. The col-IV level in samples collected from a hospital was assessed by the chemiluminescence assay. Satisfactory recoveries were obtained ranging from 93.30% to 100.14%. In conclusion, the magnetic bead-based chemiluminescence assay may be used as a routine and efficient tool to detect type IV collagen in clinical diagnosis.
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Colágeno Tipo IV , Luminescência , Humanos , Fibrose , Cirrose Hepática , Imunoensaio/métodosRESUMO
Amultifunctional liposomal polydopamine nanoparticle (MPM@Lipo) was designed in this study, to combine chemotherapy, photothermal therapy (PTT) and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis (RA) treatment. MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia, thus contributing to the repolarization of M1 macrophages into M2 phenotype. Furthermore, MPM@Lipo could accumulate at inflammatory joints, inhibit the production of inflammatory factors, and protect cartilage in vivo, effectively alleviating RA progression in a rat adjuvant-induced arthritis model. Moreover, upon laser irradiation, MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen, resulting in excellent RA treatment effects. Overall, the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.
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Rheumatoid arthritis (RA) is a severe autoimmune disease with symptoms including synovial inflammation, cartilage erosion, and bone loss in RA lesions, which eventually lead to joint deformity and function loss. Most current treatments fail to achieve satisfying therapeutic outcomes with some adverse effects. Extracellular vesicles derived from apoptotic cells (apoEVs) have emerged as important mediators in intercellular communication regulating diverse physiological and pathological processes. In this study, we investigated the therapeutic efficacy of macrophage-derived and osteoclast-derived apoEVs (Mφ-apoEVs and OC-apoEVs) on RA. The in vitro results showed that both Mφ-apoEVs and OC-apoEVs induced macrophage repolarization toward the anti-inflammatory M2 phenotype, promoted chondrocyte functions and chondrogenesis, and inhibited osteoclast formation and maturation. In addition, OC-apoEVs promoted osteogenic differentiation. The in vivo study on the CIA mouse model further demonstrated that apoEVs could couple various functions and exert synergistic effects on the joint with RA, as evidenced by the regression of synovial inflammation, the reversal of cartilage damage and bone erosion, and the preservation of joint structure. These findings demonstrated that Mφ-apoEVs and OC-apoEVs contributed to restoring the homeostasis of the overall microenvironment in the RA joint and highlighted their potential application as a promising alternative to treat RA.
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INTRODUCTION AND IMPORTANCE: The elbow is one of the most mobile joints, and its movement is very important. Bony ankylosed elbow is an uncommon condition leading to complete loss of activity of elbow, and then lead to severe disability and limitation in activities of daily living. CASE PRESENTATION: A 63-year-old woman sustained comminuted fracture of left distal humerus. She underwent open reduction and internal fixation by plates. After the plates were removed in 2016ï¼stiffness developed.The elbow was stable but fixed at 90°ï¼there was no vascular injury or deficit in sensory and motor function of the ulnar nerve. She hopes to eliminate pain and restore normal mobility compatible with ADL. CLINICAL DISCUSSION: Complete bony ankylosis of the elbow joint may be caused by trauma, rheumatic disease, burns, congenital stiffness and other conditions. Even with the compensation of shoulder and wrist, it will still have a great impact on upper limb function. Whether to treat mainly depends on whether the patient has the require to improve the functionality and return to daily activities. Treatment methods are very limited, including interposition arthroplasty and TEA. Defect of soft tissue appeared was seen in our case, Hernia Patch was innovatively applied to reconstruct the defect of soft tissue and maintain continuity of elbow extension mechanism. CONCLUSION: Patients with post-traumatic elbow joint ankylosis were suffered from severe bony abnormalities, but also soft tissue contracture or defects due to multiple operations and trauma. We present a case of complete bony ankylosed elbow treated with total elbow arthroplasty and Hernia Patch.
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Macrophages are important immune effector cells which participate various physiological and pathological conditions. Numerous studies have demonstrated the regulation of macrophage phenotype by micropatterns. It is well accepted that micropatterns affect cellular behaviors through changing cell shape and modulating the associated mechanical sensors on the plasma membrane and cytoskeleton. However, the role of nucleus, which serves as a critical physical sensing device, is often ignored. Herein, we found the nuclear deformation and the subsequently increased chromosomal histone methylation (H3K36me2) may contribute to the micropattern-induced suppression of macrophage inflammatory responses. Specifically, macrophages on micropatterned surfaces expressed lower levels of key inflammatory genes, compared with those on flat surfaces. Further investigation on macrophage nuclei showed that micropatterned surfaces cause shrinkage of nucleus volume and compaction of chromatin. Moreover, micropatterned surfaces elevated the methylation level of H3K36me2 in macrophages, while decreased the methylation level of H3K4me3. Our study provides new mechanistic insight into how micropatterns affect macrophage phenotype and highlights the importance of nuclear shape and chromatin histone modification in mediating micropattern-induced change in cell behaviors.
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Código das Histonas , Lipopolissacarídeos , Macrófagos/metabolismo , Citoesqueleto , Cromatina/metabolismoRESUMO
ABSTRACT: We describe FDG PET/CT findings in a case of isolated skull metastasis with spiculated periosteal reaction from rectal mucinous adenocarcinoma 8 years after proctectomy. The skull metastasis showed heterogeneous FDG uptake and multiple short spicules of bone producing the sunburst appearance resembling primary osteosarcoma or Ewing sarcoma. Familiarity with this atypical imaging appearance of the bone metastasis from rectal cancer may be helpful for the diagnosis and differential diagnosis.
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Neoplasias Ósseas , Osteossarcoma , Neoplasias Retais , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Crânio , Compostos RadiofarmacêuticosRESUMO
Introduction: Koumine (KME) is the most abundant active ingredient separated from Gelsemium elegans Benth and exhibits a significant therapeutic effect on rheumatoid arthritis (RA). It is a lipophilic compound with poor aqueous solubility, and there is an urgent need to develop novel dosage forms of KME and promote its clinical application for the treatment of RA. The aim of this study was to design and develop KME-loaded microemulsions (KME-MEs) for the effective management of RA. Methods: The composition of the microemulsion was selected by carrying out a solubility study and generating pseudoternary phase diagrams, and further optimized by D-Optimal design. The optimized KME-MEs was evaluated for particle size, viscosity, drug release, storage stability, cytotoxicity, cellular uptake, Caco-2 cell transport and everted gut sac investigations. In vivo fluorescence imaging and the therapeutic effects of KME and KME-MEs on collagen-induced arthritis (CIA) rats were also evaluated. Results: The optimized microemulsion contained 8% oil, 32% Smix (surfactant/cosurfactant) and 60% water and was used for in vivo and in vitro studies. The optimal KME-MEs exhibited a small globule size of 18.5 ± 0.14 nm and good stability over 3 months, and the release kinetics followed a first-order model. These KME-MEs had no toxic effect on Caco-2 cells but were efficiently internalized into the cytoplasm. Compared to KME, the KME-MEs displayed significantly increased permeability and absorption in Caco-2 cell monolayer assay and ex vivo everted gut sac experiment. As expected, the KME-MEs attenuated the progression of RA in CIA rats and were more effective than free KME with a reduced frequency of administration. Conclusion: The KME-MEs improved the solubility and therapeutic efficacy of KME by employing formulation technology. These results provide a promising vehicle for the oral delivery of KME to treat RA and have attractive potential for clinical translation.
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Artrite Experimental , Artrite Reumatoide , Animais , Ratos , Humanos , Células CACO-2 , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , BioensaioRESUMO
Osteoarthritis seriously affects the health of elderly individuals. In this study, hyaluronic acid-gold nano-optical probes (HA-GNPs) were prepared, and their effect on osteoarthritis and its underlying mechanism were explored. The HA-GNPs were synthesised via a one-step synthesis method and characterised and detected via ultraviolet-visible spectrophotometry, dynamic light scattering (particle size analysis), zeta potential analysis, and scanning and transmission electron microscopy. The cytotoxicity of the probes was determined using CCK-8 detection, fluorescent staining of dead and living cells, and an in vivo animal model, and related staining methods were established to identify the potential therapeutic capabilities of the probes. Our study showed that the synthesised HA-GNPs were more stable and suitable for probe construction than traditional sodium citrate-gold nanoparticles. The HA-GNPs were also found to be biocompatible and suitable for in vitro and in vivo experiments and clinical applications. These findings showed that HA-GNPs exert a substantial inhibitory effect on osteoarticular chondrocytes and offer a promising method for improving healing from osteoarthritis in the clinical setting in the future.
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Nanopartículas Metálicas , Osteoartrite , Animais , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Ácido Hialurônico , Osteoartrite/tratamento farmacológico , Microscopia Eletrônica de TransmissãoRESUMO
Osteosarcoma (OS) is the most common malignant tumor of the bone tissue with the lowest survival rate among all pediatric cancers. OS cells grow vigorously under malnutrition; however, the mechanism by which they adapt to metabolic stress via metabolic reprogramming remains undefined. Here, we demonstrated that USP33, a member of the DUBs family, was significantly upregulated in the tissues of patients with OS compared to normal tissues. Moreover, high USP33 expression was significantly associated with poor survival. Functional assays suggested that USP33 promoted OS cell growth through the induction of aerobic glycolysis. Additionally, we confirmed that 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) was critical for USP33-induced proliferation and aerobic glycolysis in OS cells, and the protein expression levels of PFKFB3 and USP33 were positively correlated in the OS tissues. Mechanistically, USP33 stabilized the expression of PFKFB3 by suppressing the ubiquitin mediated PFKFB3 degradation. Collectively, these findings reveal a mechanism by which OS cells survive in a dystrophic tumor microenvironment, with the USP33-PFKFB3 axis as a critical driver of aerobic glycolysis and OS proliferation. Furthermore, these findings reveal novel insights into the adaptation of cancer cells to metabolic stress in OS.
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The low level of T-lymphocyte infiltration in tumor is a key issue in cancer immunotherapy. Stimulating anti-tumor immune responses and improving the tumor microenvironment are essential for enhancing anti-PD-L1 immunotherapy. Herein, atovaquone (ATO), protoporphyrin IX (PpIX), and stabilizer (ATO/PpIX NPs) were constructed to self-assemble with hydrophobic interaction and passively targeted to tumor for the first time. The studies have indicated that PpIX-mediated photodynamic induction of immunogenic cell death combined with relieving tumor hypoxia by ATO, leading to maturation of dendritic cells, polarization of M2-type tumor-associated macrophages (TAMs) towards M1-type TAMs, infiltration of cytotoxic T lymphocytes, reduction of regulatory T cells, release of pro-inflammatory cytokines, resulting in an effective anti-tumor immune response synergized with anti-PD-L1 against primary tumor and pulmonary metastasis. Taken together, the combined nanoplatform may be a promising strategy to enhance cancer immunotherapy.
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Neoplasias Pulmonares , Neoplasias , Humanos , Nanomedicina , Imunoterapia , Neoplasias/tratamento farmacológico , Linfócitos T Citotóxicos , Neoplasias Pulmonares/metabolismo , Hipóxia , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
Myofibroblasts, the primary effector cells for implant-induced fibrosis, contribute to this process by secreting excessive collagen-rich matrix and contracting. Thus, approaches that suppress myofibroblasts may achieve desirable suppression effects in the fibrotic process. As one of the important physical properties of materials, material topographical structures have been proven to affect various aspects of cell behaviors, so is it possible to manipulate the formation of myofibroblasts by tailoring the topographical properties of medical devices? In this study, polycaprolactone (PCL) surfaces with typical micropatterns (micro column and micro pit) were fabricated. The regulatory effects of surface micropatterns on the myofibroblastic differentiation of fibroblasts were investigated. Compared to the flat surfaces and surfaces with micro pit, surfaces with micro columns triggered the F- to G-actin transition, inhibiting the nuclear transfer of myocardin-related transcription factor-A. Subsequently, the downstream gene α-smooth muscle actin, which is a marker of myofibroblasts, was suppressed. Further in vivo investigation showed that PCL implants with micro-column-patterned surfaces inhibited the formation of peri-implant fibrotic capsules. Our results demonstrate that surface topographical properties are a potent regulator of fibroblast differentiation into myofibroblasts and highlight the antifibrotic potential of modifying surfaces with micro-column patterns.
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Interleukin-18 (IL-18), a member of IL-1 cytokine superfamily, is deemed as an important indicator of the kidney disease. Herein a sandwich chemiluminescence immunoassay integrated with magnetic beads was conducted to detect IL-18 in kidney disease. The detection limit and linear range were 0.0044 ng/mL and 0.01-2.7 ng/mL, respectively. Satisfactory recoveries were ranged from 91.70 to 101.18% with the relative standard deviation below 10%; interference bias of most biomarkers were within allowable deviation range (± 15%). In summary, the whole study was successfully applied to detect IL-18 levels in urine samples for patients with kidney disease. The results showed that chemiluminescence immunoassay for IL-18 detection could be used in the clinical application.
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Interleucina-18 , Nefropatias , Humanos , Imunoensaio/métodos , Luminescência , Biomarcadores , Medições Luminescentes/métodosRESUMO
To develop next-generation nanomedicine, theranostic nanotherapeutic strategies are increasingly being emphasized. In recent years, it is observed that the effective lifetime of anti-bacterial and anti-cancer agent is diminishing, which undermines the economic incentives necessary for clinical development and therapeutic applications. Thus, novel formulations ought to not only kill drug resistant strains and cancerous cells but also inhibit their formation. Recently, metallic nanoparticles [for example- silver (Ag) nanoparticles] have been widely investigated for their biomedical applications. The so-called applications necessitate the inclusion of these nanoparticles inside polymeric matrices (for example- dendrimer) leading to chemical functionalization of the metallic nanoparticles. Silver and silver nanoparticles' antibacterial activity has already been well established over years. Dendrimers due to their homogeneous highly branched structure and uniform composition are perfectly suitable for the inclusion of silver nanoparticles [Ag NPs]. Recently, the increasing trend in the development of Ag-dendrimer nanocomposites is attributed to the excellent antibacterial activity of Ag as well as dendrimer's unique properties like variable functional terminal ends and potential antibacterial effect necessarily. This review provides an informative overview regarding the numerous aspects of bactericidal and other biomedical applications of Ag-dendrimer nanocomposites, particularly emphasizing analysis of existing research and prospective worth to the pharmaceutical sector in future.
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Dendrímeros , Nanopartículas Metálicas , Nanocompostos , Humanos , Nanopartículas Metálicas/química , Prata/farmacologia , Prata/química , Estudos Prospectivos , Nanocompostos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , BactériasRESUMO
Background: The most prevalent malignant tumor in a human brain nervous system is called glioma. Peptide is a compound formed by the peptide bond of α-amino acids, and the development of polypeptide drugs has been widely used in many fields. We plan to investigate the underlying peptides with clinical value in glioma. Method: Based on public databases, we targeted the common genes between glioma differentially expressed genes (DEGs) and peptide genes related to glioma prognosis. Then, these common genes were analyzed by LASSO-Cox analysis, prognostic risk model, and nomogram to identify key prognostic peptide genes and the target gene in this study. Next, the mechanism of target gene in glioma was explored by bioinformatics analysis and functional experiments. Results: We obtained a total of 26 overlapping genes for the following study. After that, 6 independent prognostic factors (REPIN1, PSD3, RDX, CDK4, FANCI, and ARHGEF9) were obtained and applied to construct the prognostic nomogram, and ARHGEF9 was the target gene in the study. Next, peptide ARHGEF9 was found to inhibit glioma cell development. Through Spearman's correlation analysis, ARHGEF9 had a close relation with PI3K/AKT/mTOR pathway. In functional experiments, peptide ARHGEF9 could suppress the protein expressions of p-PIK3K, p-AKT and p-mTOR, while IGF-1 could reverse this effect. Conclusion: This study identifies 6 new prognostic biomarkers for glioma patients. Among them, peptide ARHGEF9 gene is an inhibitory gene functioning by targeting PI3K/AKT/mTOR pathway.
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Anemia de Fanconi , Glioma , Humanos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Glioma/tratamento farmacológico , Glioma/genética , Aminoácidos , Serina-Treonina Quinases TOR/genética , Fatores de Troca de Nucleotídeo Guanina RhoRESUMO
Liver fatty acid binding protein (L-FABP) is an intercellular lipid chaperone protein that selectively combines with unsaturated free fatty acids and transports them to mitochondria or peroxisomes. L-FABP is a promising biomarker for the early detection of renal diseases in humans. Herein a chemiluminescence method (CLIA) was demonstrated to measure the level of urinary L-FABP in the urinary samples. An anti-(L-FABP)-magnetic beads complex was prepared to capture the analyte target. Sensitivity, precision, accuracy, interference effect, high-dose hook effect of the developed assay were evaluated. Under the suitable experimental parameters, the established method have a wide linear range (0.01-10 ng/mL) and also showed a sufficiently low limit of detection of 0.0060 ng/mL. Besides, the satisfactory recoveries of the method in the urinary were ranged from 97.74%-112.32%, which was well within the requirement of clinical analysis. Furthermore, this proposed method has been successfully applied to the clinical determination of L-FABP in patients who have been diagnosed with kidney disease. The results showed that CLIA could accurately and rapidly determine the urinary level of L-FABP with high-throughput, which could be useful as a new tool to predict complications in patients with kidney disease. The clinical trial was approved by Shuyang Hospital of Traditional Chinese Medicine Ethics Committee: 20,210,202-001 at February 2, 2021.