ABSTRACT
Small extracellular vesicle-associated microRNAs (sEV-miRNAs) have emerged as critical biomarkers for cancer diagnosis, yet the rapid detection of these low-abundance molecules in clinical samples remains a formidable challenge. Herein, a simple turbo-like localized catalytic hairpin assembly (TL-CHA) was proposed for sEV-miR-1246 measurement. This electrochemical sensor achieves dual localization through the ingeniously use of AuNPs and DNA nanowires, which provides rich sites for CHA cascade amplification, significantly enhancing the effective reaction and amplify the detection response. Leveraging this innovative design, this biosensor demonstrated the ability to detect sEV-miRNA at concentrations as low as 5.24 aM in a time frame of 30 min. The precision of the measurements was validated through reverse transcription quantitative polymerase chain reaction. Furthermore, the sensor was used for analyzing plasma samples from gastric cancer patients yielded AUC values of 0.973 for all stages and 0.945 for early stages. This demonstrates the sensor's robust performance in both the staging diagnosis and early screening of gastric cancer. Therefore, this platform has great potential for the clinical cancer diagnosis.
Subject(s)
Biosensing Techniques , Electrochemical Techniques , Gold , MicroRNAs , Biosensing Techniques/methods , Electrochemical Techniques/methods , MicroRNAs/blood , MicroRNAs/analysis , Humans , Gold/chemistry , Metal Nanoparticles/chemistry , Stomach Neoplasms/diagnosis , Stomach Neoplasms/blood , Limit of Detection , Catalysis , Nanowires/chemistryABSTRACT
DNA nanostructures, known for their programmability, ease of modification, and favourable biocompatibility, have gained widespread application in the biomedical field. Among them, Tetrahedral DNA Origami (TDOs), as a novel DNA nanostructure, possesses well-defined structures, multiple modification sites, and large cavities, making it a promising drug carrier. However, current understanding of TDOs' interactions with biological systems, particularly with target cells and organs, remains unexplored, limiting its further applications in biomedicine. In this work, we prepared TDOs with an average particle size of 40 nm and labelled them with Cy5 fluorescent molecules. Following intravenous injection in mice, the uptake of TDOs by different types of liver and kidney cells was observed. Results indicated that TDOs accumulate in renal tubules and are metabolized by Kupffer cells, epithelial cells, and hepatocytes in the liver. Additionally, in a tumour-bearing mouse model, TDOs passively targeted tumour tissues and exhibited excellent tumour penetration and retention after rapid metabolism in hepatocytes. Our findings provide crucial insights for the development of TDO-based drug delivery systems.
Subject(s)
DNA , Kidney , Liver , Nanostructures , Animals , Mice , DNA/metabolism , Liver/metabolism , Humans , Kidney/metabolism , Nanostructures/chemistry , Hepatocytes/metabolism , Carbocyanines/chemistry , Mice, Inbred BALB C , Cell Line, TumorABSTRACT
The intracellular clustering of anisotropic nanoparticles is crucial to the improvement of the localized surface plasmon resonance (LSPR) for phototherapy applications. Herein, we programmed the intracellular clustering process of spiky nanoparticles (SNPs) by encapsulating them into an anionic liposome via a frame-guided self-assembly approach. The liposome-encapsulated SNPs (lipo-SNPs) exhibited distinct and enhanced lysosome-triggered aggregation behavior while maintaining excellent monodispersity, even in acidic or protein-rich environments. We explored the enhancement of the photothermal therapy performance for SNPs as a proof of concept. The photothermal conversion efficiency of lipo-SNPs clusters significantly increased 15 times compared to that of single lipo-SNPs. Upon accumulation in lysosomes with a 2.4-fold increase in clustering, lipo-SNPs resulted in an increase in cell-killing efficiency to 45% from 12% at 24 µg/mL. These findings indicated that liposome encapsulation provides a promising approach to programing nanoparticle clustering at the target site, which facilitates advances in the development of smart nanomedicine with programmable enhancement in LSPR.
Subject(s)
Liposomes , Nanoparticles , Phototherapy/methods , Surface Plasmon Resonance , NanomedicineABSTRACT
Regulation of excessive inflammation and impaired cell proliferation is crucial for healing diabetic wounds. Although plant-to-mammalian regulation offers effective approaches for chronic wound management, the development of a potent plant-based therapeutic presents challenges. This study aims to validate the efficacy of turmeric-derived nanoparticles (TDNPs) loaded with natural bioactive compounds. TDNPs can alleviate oxidative stress, promote fibroblast proliferation and migration, and reprogram macrophage polarization. Restoration of the fibroblast-macrophage communication network by TDNPs stimulates cellular regeneration, in turn enhancing diabetic wound healing. To address diabetic wound management, TDNPs are loaded in an ultralight-weight, high swelling ratio, breathable aerogel (AG) constructed with cellulose nanofibers and sodium alginate backbones to obtain TDNPs@AG (TAG). TAG features wound shape-customized accessibility, water-adaptable tissue adhesiveness, and capacity for sustained release of TDNPs, exhibiting outstanding performance in facilitating in vivo diabetic wound healing. This study highlights the potential of TDNPs in regenerative medicine and their applicability as a promising solution for wound healing in clinical settings.
Subject(s)
Curcuma , Diabetes Mellitus, Experimental , Nanoparticles , Wound Healing , Wound Healing/drug effects , Animals , Nanoparticles/chemistry , Curcuma/chemistry , Mice , Disease Models, Animal , Cell Proliferation/drug effects , Gels , Rats , Fibroblasts/drug effects , Fibroblasts/metabolismABSTRACT
BACKGROUND: Lupus nephritis (LN) is a type of autoimmune disease that impacts the kidneys. Exosomes are valuable for in-depth studies of the pathogenesis of LN. This study aimed to explore miR-181d-5p expression levels in M0 macrophage-derived exosomes and their role in human renal mesangial cells (HRMC) pyroptosis through binding to BCL-2. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from patients with lupus nephritis (LN) and healthy subjects. Monocytes isolated from these samples were induced into M0 macrophages using recombinant human granulocyte colony-stimulating factor (rhG-CSF). In a parallel process, THP-1 cells were induced into M0 macrophages using Phorbol Myristate Acetate (PMA). LPS- and ATP-stimulated HRMC were used to construct a cell pyroptosis model. We then introduced different miR-181d-5p mimic fragments into the M0 macrophages derived from the THP-1 cells. Subsequently, exosomes from these macrophages were co-cultured with HRMC. To evaluate the impact on HRMC, we conducted proliferation and apoptosis assessments using CellCountingKit-8assay and flow cytometry. The effect of exosomal miR-181d-5p on HRMC pyroptosis was assessed using western blot. The miR-181d-5p and BCL-2 targeting relationship was detected using real-time fluorescence quantitative PCR. IL-6, IL-1ß, and TNF-α levels in cell supernatants were detected using ELISA kits. RESULTS: In this study, we observed an increase in miR-181d-5p levels within exosomes secreted from M0 macrophages obtained by induction of monocytes from LN patients. It was found that miR-181d-5p can target binding to BCL-2. Exosomes with elevated levels of miR-181d-5p contributed to a significant increase in miR-181d-5p within HRMC, facilitating its proliferation and inhibiting apoptosis. Furthermore, exosomes expressing high levels of miR-181d-5p were observed to promote an inflammatory response and pyroptosis in HRMC. Notably, these effects were reversed when the levels of miR-181d-5p in the exosomes were reduced. CONCLUSION: Inhibition of miR-181d-5p, derived from M0 macrophage exosomes, effectively suppresses inflammation and pyroptosis in HRMC. This discovery indicates that miR-181d-5p holds the potential as a valuable target in the development of treatments for Lupus Nephritis (LN).
Subject(s)
Exosomes , Lupus Nephritis , MicroRNAs , Humans , Caspase 1/genetics , Mesangial Cells , Pyroptosis/genetics , Lupus Nephritis/genetics , Exosomes/genetics , Leukocytes, Mononuclear , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Macrophages , MicroRNAs/genetics , Gasdermins , Phosphate-Binding ProteinsABSTRACT
The capacity to identify small amounts of pathogens in real samples is extremely useful. Herein, we proposed a sensitive platform for detecting pathogens using cyclic DNA nanostructure@AuNP tags (CDNA) and a cascade primer exchange reaction (cPER). This platform employs wheat germ agglutinin-modified Fe3O4@Au magnetic nanoparticles (WMRs) to bind the E. coli O157:H7, and then triggers the cPER to generate branched DNA products for CDNA tag hybridization with high stability and amplified SERS signals. It can identify target pathogens as low as 1.91 CFU/mL and discriminate E. coli O157:H7 in complex samples such as water, milk, and serum, demonstrating comparable or greater sensitivity and accuracy than traditional qPCR. Moreover, the developed platform can detect low levels of E. coli O157:H7 in mouse serum, allowing the discrimination of mice with early-stage infection. Thus, this platform holds promise for food analysis and early infection diagnosis.
Subject(s)
Escherichia coli O157 , Nanoparticles , Animals , Mice , DNA, Complementary , DNA , Escherichia coli O157/genetics , Food MicrobiologyABSTRACT
Detecting low-frequency DNA mutations hotspots cluster is critical for cancer diagnosis but remains challenging. Quantitative PCR (qPCR) is constrained by sensitivity, and allele-specific PCR is restricted by throughput. Here we develop a long blocker displacement amplification (LBDA) coupled with qPCR for ultrasensitive and multiplexed variants detection. By designing long blocker oligos to perfectly match wildtype sequences while mispairing with mutants, long blockers enable 14-44â nt enrichment regions which is 2-fold longer than normal BDA in the experiments. For wild template with a specific nucleotide, LBDA can detect different mutation types down to 0.5 % variant allele frequency (VAF) in one reaction, with median enrichment fold of 1,000 on 21â mutant DNA templates compared to the wild type. We applied LBDA-qPCR to detect KRAS and NRAS mutation hotspots, utilizing a single plex assay capable of covering 81â mutations and tested in synthetic templates and colorectal cancer tissue samples. Moreover, the mutation types were verified through Sanger sequencing, demonstrating concordance with results obtained from next generation sequencing. Overall, LBDA-qPCR provides a simple yet ultrasensitive approach for multiplexed detection of low VAF mutations hotspots, presenting a powerful tool for cancer diagnosis and monitoring.
Subject(s)
Mutation , Humans , Proto-Oncogene Proteins p21(ras)/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/diagnosis , Membrane Proteins/genetics , Nucleic Acid Amplification Techniques/methods , GTP Phosphohydrolases/geneticsABSTRACT
Generally, two-dimensional gold nanomaterials have unique properties and functions that offer exciting application prospects. However, the crystal phases of these materials tend to be limited to the thermodynamically stable crystal structure. Herein, we report a DNA framework-templated approach for the ambient aqueous synthesis of freestanding and microscale amorphous gold nanosheets with ultrathin sub-nanometer thickness. We observe that extended single-stranded DNA on DNA nanosheets can induce site-specific metallization and enable precise modification of the metalized nanostructures at predefined positions. More importantly, the as-prepared gold nanosheets can serve as an electrocatalyst for glucose oxidase-catalyzed aerobic oxidation, exhibiting enhanced electrocatalytic activity (~3-fold) relative to discrete gold nanoclusters owing to a larger electrochemical active area and wider band gap. The proposed DNA framework-templated metallization strategy is expected to be applicable in a broad range of fields, from catalysis to new energy materials.
Subject(s)
Gold , Nanostructures , Gold/chemistry , Nanostructures/chemistry , Oxidation-Reduction , DNA , WaterABSTRACT
Breast cancer has overtaken lung cancer as the number one cancer worldwide. Paclitaxel (PTX) is a widely used first-line anti-cancer drug, but it is not very effective in clinical breast cancer therapy. It has been reported that triptolide (TPL) can enhance the anticancer effect of paclitaxel, and better synergistic therapeutic effects are seen with concomitant administration of PTX and TPL. In this study, we developed pH-responsive polymeric micelles for co-delivery of PTX and TPL, which disassembling in acidic tumour microenvironments to target drug release and effectively kill breast cancer cells. Firstly, we synthesized amphiphilic copolymer mPEG2000-PBAE through Michael addition reaction, confirmed by various characterizations. Polymer micelles loaded with TPL and PTX (TPL/PTX-PMs) were prepared by the thin film dispersion method. The average particle size of TPL/PTX-PMs was 97.29 ± 1.63 nm, with PDI of 0.237 ± 0.003 and Zeta potential of 9.57 ± 0.80 mV, LC% was 6.19 ± 0.21%, EE% was 88.67 ± 3.06%. Carrier material biocompatibility and loaded micelle cytotoxicity were assessed using the CCK-8 method, demonstrating excellent biocompatibility. Under the same drug concentration, TPL/PTX-PMs were the most toxic to tumour cells and had the strongest proliferation inhibitory effect. Cellular uptake assays revealed that TPL/PTX-PMs significantly increased intracellular drug concentration and enhanced antitumor activity. Overall, pH-responsive micellar co-delivery of TPL and PTX is a promising approach for breast cancer therapy.
Subject(s)
Breast Neoplasms , Diterpenes , Epoxy Compounds , Micelles , Paclitaxel , Phenanthrenes , Polymers , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/administration & dosage , Epoxy Compounds/chemistry , Phenanthrenes/chemistry , Phenanthrenes/pharmacology , Phenanthrenes/administration & dosage , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Paclitaxel/pharmacology , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Paclitaxel/chemistry , Hydrogen-Ion Concentration , Female , Polymers/chemistry , Drug Carriers/chemistry , MCF-7 Cells , Drug Liberation , Cell Line, Tumor , Polyethylene Glycols/chemistry , Cell Survival/drug effects , Cell Proliferation/drug effectsABSTRACT
Cancer's high incidence and death rate jeopardize human health and life, and it has become a global public health issue. Some members of NPCs have been studied in a few cancers, but comprehensive and prognostic analysis is lacking in most cancers. In this study, we used the Cancer Genome Atlas (TCGA) data genomics and transcriptome technology to examine the differential expression and prognosis of NPCs in 33 cancer samples, as well as to investigate NPCs mutations and their effect on patient prognosis and to evaluate the methylation level of NPCs in cancer. The linked mechanisms and medication resistance were subsequently investigated in order to investigate prospective tumor therapy approaches. The relationships between NPCs and immune infiltration, immune cells, immunological regulatory substances, and immune pathways were also investigated. Finally, the LUAD and KICH prognostic prediction models were built using univariate and multivariate COX regression analysis. Additionally, the mRNA and protein levels of NPCs were also identified.
Subject(s)
Lung Neoplasms , Neoplasms , Humans , Prospective Studies , Genomics , Multivariate Analysis , Mutation , Neoplasms/genetics , Prognosis , Niemann-Pick C1 Protein , Vesicular Transport Proteins , Membrane Transport ProteinsABSTRACT
Rapid detection of prostate-specific antigen (PSA) is pivotal for the early screening of prostate cancer (PCa). Here, we devise a one-step, amplification-free fluorescent detection strategy for PSA, employing the trans-cleavage principle of a CRISPR-Cas12a-aptamer system. This method offers a linear range of 0.31-5 ng mL-1 and a detection limit of 0.16 ng mL-1. The high-confidence quantification of PSA is demonstrated through the analysis of real samples, effectively distinguishing between PCa patients and healthy individuals.
Subject(s)
Biosensing Techniques , Prostatic Neoplasms , Male , Humans , CRISPR-Cas Systems/genetics , Prostate-Specific Antigen , Coloring Agents , Oligonucleotides , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/geneticsABSTRACT
Intravitreal injection is widely employed for the treatment of retinal diseases. However, it suffers from various drawbacks, including ocular trauma, risk of infection, and poor patient compliance due to frequent administrations. Due to the presence of barriers such as the cornea, it has been a challenge to develop efficient noninvasive ophthalmic eye drops that can reach the retina. Framework nucleic acids (FNAs), known for their excellent biocompatibility and precise, controllable shape and size, have been extensively utilized in drug delivery application. Here, we report the development of size- and shape-resolved fluorescent DNA frameworks for noninvasive retinal administration. Results show that tetrahedral DNA nanostructures (TDNs) with an edge length of 20 bp can reach the retina within 6 h with the highest efficiency. Moreover, this delivery method exhibits excellent biocompatibility. Our findings provide an approach for the development of localized treatment strategies for retinal diseases using FNA-based nanocarriers.
Subject(s)
Nucleic Acids , Retinal Diseases , Humans , Nucleic Acids/therapeutic use , Ophthalmic Solutions , Retina , DNA/chemistryABSTRACT
Arthritis is a joint disorder that potentially causes permanent joint damage and eventual disability without effective treatment. Clinical detection methods, including in vitro blood tests and anatomical imaging, still have limitations in achieving real-time in situ early detection of arthritis. In this work, a dual-channel luminescence nanoprobe (AGNPs-Cy7) is reported, which combines a cyanine dye and a photochemical reaction-based afterglow system for real-time in vivo imaging of arthritis. AGNPs-Cy7 simultaneously detect hypochlorous acid (HOCl) and temperature, two important indicators associated with the early development of arthritis, by monitoring the respective changes in independent ratiometric fluorescence and afterglow lifetime signals. The anti-interference properties of both the ratiometric fluorescence signal and afterglow lifetime signal enhance sensing accuracy compared to the single luminescence intensity. The developed probe successfully reveals the simultaneous increase in HOCl concentration and temperature in an arthritis mouse model.
ABSTRACT
Small extracellular-vesicule-associated microRNA (sEV-miRNA) is an important biomarker for cancer diagnosis. However, rapid and sensitive detection of low-abundance sEV-miRNA in clinical samples is challenging. Herein, a simple electrochemical biosensor that uses a DNA nanowire to localize catalytic hairpin assembly (CHA), also called domino-type localized catalytic hairpin assembly (DT-LCHA), has been proposed for sEV-miRNA1246 detection. The DT-LCHA offers triple amplification, (i). CHA system was localized in DNA nanowire, which shorten the distance between hairpin substrate, inducing the high collision efficiency of H1 and H2 and domino effect. Then, larger numbers of CHAs were triggered, capture probe bind DT-LCHA by exposed c sites. (ii) The DNA nanowire can load large number of electroactive substance RuHex as amplified electrochemical signal tags. (iii) multiple DT-LCHA was carried by the DNA nanowire, only one CHA was triggered, the DNA nanowire was trapped by the capture probe, which greatly improve the detection sensitivity, especially when the target concentration is extremely low. Owing to the triple signal amplification in this strategy, sEV-miRNA at a concentration of as low as 24.55 aM can be detected in 20 min with good specificity. The accuracy of the measurements was also confirmed using reverse transcription quantitative polymerase chain reaction. Furthermore, the platform showed good performance in discriminating healthy donors from patients with early gastric cancer (area under the curve [AUC]: 0.96) and was equally able to discriminate between benign gastric tumors and early cancers (AUC: 0.77). Thus, the platform has substantial potential in biosensing and clinical diagnosis.
Subject(s)
MicroRNAs , Humans , Anilides , Catalysis , LeucineABSTRACT
The DNA frame structure as a natural shell to stably shield the sequence-templated Ag nanocluster core (csAgNC) is intriguing yet challenging for applicable fluorescence biosensing, for which the elaborate programming of a cluster scaffold inside a DNA-based cage to guide csAgNC nucleation might be crucial. Herein, we report the first design of a symmetric tetrahedral DNA nanocage (TDC) that was self-assembled in a one-pot process using a C-rich csAgNC template strand and four single strands. Inside the as-constructed soft TDC architecture, the template sequence was logically bridged from one side to another, not in the same face, thereby guiding the in situ synthesis of emissive csAgNC. Because of the strong electron-repulsive capability of the negatively charged TDC, the as-formed csAgNC displayed significantly improved fluorescence stability and superb spectral behavior. By incorporating the recognizable modules of targeted microRNAs (miRNAs) in one vertex of the TDC, an updated TDC (uTDC) biosensing platform was established via the photoinduced electron transfer effect between the emissive csAgNC reporter and hemin/G-quadruplex (hG4) conjugate. Because of the target-interrupted csAgNC switching in three states with the spatial proximity and separation to hG4, an "on-off-on" fluorescing signal response was executed, thus achieving a wide linear range to miRNAs and a limit of detection down to picomoles. Without complicated chemical modifications, this simpler and more cost-effective strategy offered accurate cell imaging of miRNAs, further suggesting possible therapeutic applications.
ABSTRACT
Aluminum chloride is an inorganic polymeric coagulant commonly found in daily life and various materials. Although male reproductive toxicity has been associated with AlCl3 exposure, the underlying mechanism remains unclear. This study aimed to examine the impact of AlCl3 exposure on mitophagy and mitochondrial apoptosis in testicular tissue and mouse spermatocytes. Reactive oxygen species (ROS) and ATP levels were measured in GC-2spd after AlCl3 exposure using a multifunctional enzyme labeler. The changes in mitochondrial membrane potential (MMP) and TUNEL were observed through confocal laser microscopy, and the expression of proteins associated with mitophagy and apoptosis was analyzed using Western blot. Our results demonstrated that AlCl3 exposure disrupted mitophagy and increased apoptosis-related protein expression in testicular tissues. In the in vitro experiments, AlCl3 exposure induced ROS production, suppressed cell viability and ATP production, and caused a decrease in MMP, leading to mitophagy and cell apoptosis in GC-2spd cells. Intervention with N-acetylcysteine (NAC) reduced ROS production and partially restored mitochondrial function, thereby reversing the resulting mitophagy and cell apoptosis. Our findings provide evidence that ROS-mediated mitophagy and cell apoptosis play a crucial role in the toxicity of AlCl3 exposure in GC-2spd. These results contribute to the understanding of male reproductive toxicity caused by AlCl3 exposure and offer a foundation for future research in this area.
ABSTRACT
Liver cancer is a cunning malignancy with a high incidence and mortality rate among cancers worldwide. The NPC gene family members (NPCs: NPC1, NPC2, and NPC1L1) are closely linked to the development of multiple cancers, but their role in liver cancer remains unclear. As a result, we must investigate their functions in liver hepatocellular carcinoma (LIHC). NPCs were significantly differentially expressed between normal and LIHC tissues, with a high mutation frequency in LIHC. The ROC curve analysis revealed that NPC1/NPC2 had high diagnostic and prognostic values in LIHC. NPC1 expression was also found to be negatively correlated with its methylation level. The differentially expressed genes between high and low NPC1 expression groups in LIHC were mainly related to channel activity, transporter complexes, and plasma membrane adhesion molecules. Additionally, NPC1 expression was significantly associated with multiple immune cells and immunization checkpoints. It was hypothesized that a TUG1/SNHG4-miR-148a-3p-NPC1 regulatory axis is associated with hepatocarcinogenesis. Finally, the protein expression of NPC1 in LIHC tissues and paraneoplastic tissues was detected, and NPC1-knockdown HepG2 cells (NPC1KO) inhibited the proliferation, migration, and invasion. This study helped to identify new prognostic markers and potential immunotherapeutic targets for LIHC and revealed the molecular mechanisms underlying NPC1 regulation in LIHC. The NPCs play a key role in the prognosis and diagnosis of LIHC and may be an important indicator for LIHC prognosis and diagnosis; NPC1 might be a potential therapeutic target in LIHC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Prognosis , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , MultiomicsABSTRACT
BACKGROUND: Noninvasive monitoring of cancer through circulating tumor cells (CTCs) is hampered long by unsatisfactory CTCs testing techniques. Efficient isolation of CTCs in a rapid and price-favorable way from billions of leukocytes is crucial for testing. METHODS: We developed a new method based on the stronger adhesive power of CTCs versus leukocytes to sensitively isolate CTCs. Using a BSA-coated microplate and low-speed centrifuge, this method could easily separate cancer cells within 20 min at a very low cost. RESULT: The capture ratio can reach 70.7-86.6% in various cancer cell lines (breast/lung/liver/cervical/colorectal cancer) covering different epithelial-mesenchymal transformation (EMT) phenotypes and cell sizes, demonstrating the potential for efficient pan-cancer CTCs detection. Moreover, the label-free process can well preserve cell viability (â¼99%) to fit downstream DNA/RNA sequencing. CONCLUSIONS: A novel technique for non-destructive and rapid enrichment of CTCs has been devised. It has enabled the successful isolation of rare tumor cells in the patient blood sample and pleural effusion, highlighting a promising future of this method in clinical translation.
Subject(s)
Liver Neoplasms , Lung Neoplasms , Neoplastic Cells, Circulating , Uterine Cervical Neoplasms , Humans , Female , Neoplastic Cells, Circulating/pathology , Cell Line, Tumor , Cell Separation/methods , Biomarkers, TumorABSTRACT
BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is placed important role in the therapy of complications of portal hypertension, there is still no suitable criterion for a reduction in portosystemic gradient (PSG), which can both reduce PSG and maximize clinical results and minimize hepatic encephalopathy (HE). AIM: To compare the clinical outcomes and incidence of HE after one-third PSG reduction during TIPS in patients with variceal bleeding and refractory ascites. METHODS: A total of 1280 patients with portal-hypertension-related complications of refractory ascites or variceal bleeding who underwent TIPS from January 2016 to January 2019 were analyzed retrospectively. Patients were divided into group A (variceal hemorrhage and PSG reduced by one third, n = 479); group B (variceal hemorrhage and PSG reduced to < 12 mmHg, n = 412); group C (refractory ascites and PSG reduced by one third, n = 217); and group D (refractory ascites and PSG reduced to < 12 mmHg of PSG, plus medication, n = 172). The clinical outcomes were analyzed. RESULTS: By the endpoint of follow-up, recurrent bleeding was no different between groups A and B (χ 2 = 7.062, P = 0.374), but recurrent ascites did differ significantly between groups C and D (χ 2 = 14.493, P = 0.006). The probability of total hepatic impairment within 3 years was significantly different between groups A and B (χ 2 = 11.352, P = 0.005) and groups C and D (χ 2 = 13.758, P = 0.002). The total incidence of HE differed significantly between groups A and B (χ 2 = 7.932, P = 0.016), groups C and D (χ 2 = 13.637, P = 0.007). There were no differences of survival rate between groups A and B (χ 2 = 3.376, P = 0.369, log-rank test), but did differ significantly between groups C and D (χ 2 = 13.582, P = 0.014, log-rank test). CONCLUSION: The PSG reduction by one third may reduce the risk of HE, hepatic function damage and achieve good clinical results.
Subject(s)
Esophageal and Gastric Varices , Hepatic Encephalopathy , Hypertension, Portal , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Esophageal and Gastric Varices/surgery , Esophageal and Gastric Varices/complications , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/methods , Ascites/etiology , Retrospective Studies , Gastrointestinal Hemorrhage/prevention & control , Gastrointestinal Hemorrhage/complications , Hypertension, Portal/surgery , Hypertension, Portal/complications , Hepatic Encephalopathy/epidemiology , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/prevention & control , Treatment Outcome , Liver Cirrhosis/complications , Liver Cirrhosis/surgeryABSTRACT
The application of nanodevices based on DNA self-assembly in the field of cell biology has made significant progress in the past decade. In this study, the development of DNA nanotechnology is briefly reviewed. The subcellular localization of DNA nanodevices, and their new progress and applications in the fields of biological detection, subcellular and organ pathology, biological imaging, and other fields are reviewed. The future of subcellular localization and biological applications of DNA nanodevices is also discussed.