Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine's reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context.
In this article, the method of dynamic performance monitoring and adaptive self-tuning of parameters for actual PID control systems of industrial processes in virtual reality scenes is proposed. This method combines the digital twin model of the PID control process based on system identification and adaptive deep learning and the PID tuning intelligent algorithm based on reinforcement learning with virtual reality and immersive interaction of industrial metaverse. An industrial metaverse-based intelligent PID tuning system is proposed by combining the above method with the end-edge-cloud collaboration technology of Industrial Internet. The challenging problem that the actual operating PID control system in complex industrial processes cannot be optimized online is solved. Using the energy-intensive equipment, the fused magnesium furnace, as an industrial object, we conducted comparative simulation experiments between the proposed control method and several advanced control methods, as well as industrial experiments for the proposed intelligent system. Simulation experiments demonstrate the effectiveness of the proposed control method. The industrial experimental results indicate that the performance monitoring and adaptive self-tuning of parameters for actual PID control systems of industrial processes in virtual reality scenes can be realized, which achieves excellent control effects.
Charge, spin and Cooper-pair density waves have now been widely detected in exotic superconductors. Understanding how these density waves emerge - and become suppressed by external parameters - is a key research direction in condensed matter physics. Here we study the temperature and magnetic-field evolution of charge density waves in the rare spin-triplet superconductor candidate UTe2 using scanning tunneling microscopy/spectroscopy. We reveal that charge modulations composed of three different wave vectors gradually weaken in a spatially inhomogeneous manner, while persisting to surprisingly high temperatures of 10-12 K. We also reveal an unexpected decoupling of the three-component charge density wave state. Our observations match closely to the temperature scale potentially related to short-range magnetic correlations, providing a possible connection between density waves observed by surface probes and intrinsic bulk features. Importantly, charge density wave modulations become suppressed with magnetic field both below and above superconducting Tc in a comparable manner. Our work points towards an intimate connection between hidden magnetic correlations and the origin of the unusual charge density waves in UTe2.
Background: 20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown. Methods: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance. Results: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3. Conclusions: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.
BACKGROUND: The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. METHODS: We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. RESULTS: Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III-IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200-5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021-1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III-IV cardiac function (HR = 1.945, 95% CI: 1.149-3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845-0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429-0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025-4.554, p = 0.043) increased the mortality risk after six months of USPD. CONCLUSION: Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III-IV cardiac function, WBC count, potassium, and calcium levels.
Kidney Failure, Chronic , Peritoneal Dialysis , Aged , Humans , Retrospective Studies , Calcium , Peritoneal Dialysis/adverse effects , Renal Dialysis , Potassium , Risk Factors
Nephrotoxicity induced by aristolochic acid I (AAI) is related to redox stress and apoptosis. Apurinic/apyrimidine endonuclease 1 (APE1) has antioxidant and anti-apoptotic effects. This study investigated the potential role of APE1 in AAI-induced nephrotoxicity. Renal injury was successfully induced in C57BL/6J mice by intraperitoneal injection of AAI every other day for 28 days. Expressions of APE1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) in renal tissues of the model mice was inhibited, accompanied by oxidative damage and apoptosis. Similar results were obtained in vitro in human proximal tubular (HK-2) cells damaged by AAI. In the presence of a low concentration of the APE1 inhibitor E3330, expression of Nrf2 and HO-1 proteins in HK-2 cells was decreased and AAI-induced apoptosis was aggravated. Overexpression of APE1 in HK-2 cells promoted the expression of Nrf2 and HO-1, and alleviated apoptosis and renal injury induced by AAI. The collective findings demonstrate that AAI can inhibit the induction of oxidative stress and apoptosis by the APE1/Nrf2/HO-1 axis, leading to AAI renal injury. Targeting APE1 may be an effective therapeutic strategy to treat AA nephrotoxicity.
Aristolochic Acids , NF-E2-Related Factor 2 , Mice , Humans , Animals , NF-E2-Related Factor 2/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Mice, Inbred C57BL , Oxidative Stress , Apoptosis , Aristolochic Acids/toxicity
High-entropy alloys (HEAs) have gained significant attentions in recent years, due to their unique properties derived from the combination of multiple elements in equimolar or near-equimolar ratios. The mechanical properties of HEAs are influenced by microstructural characteristics. In this study, MnCrFeCoNi HEA ribbons were produced using a technique called melt spinning, for which the wheel speed was adjusted to control the undercooling levels. The rapid solidification process under undercooling condition resulted in refined grain sizes to micrometers in the ribbons. One notable feature was the appearance of twin boundaries, which especially accounted for approximately 7.36 % of the microstructure for the ribbons produced at a wheel speed of 10 m/s. For the ribbons with thickness of micrometer scale, the mechanical properties (ultimate tensile strength up to 2.5 GPa and hardness up to 300 MPa) were analyzed by microstructure (grain boundaries and homogeneity) and exterior factors (e.g. thickness). Overall, this study provides a new approach for tailoring the microstructures and mechanical properties of HEAs via melt spinning technique. The HEA ribbons present a novel form that could potentially broaden the scope of applications for these materials.
Vincristine (VCR) is a microtubule-destabilizing chemotherapeutic agent commonly administered for the treatment of cancers in patients, which can induce severe side effects including neurotoxicity. In context of the effects on female fertility, ovarian toxicity has been found in patients and mice model after VCR exposure. However, the influence of VCR exposure on oocyte quality has not been elucidated. We established VCR exposure in vitro and in vivo model. The results indicated in vitro VCR exposure contributed to failure of oocyte maturation through inducing defects in spindle assembly, activation of SAC, oxidative stress, mitochondrial dysfunction, and early apoptosis, which were confirmed by using in vivo exposure model. Moreover, in vivo VCR exposure caused aneuploidy, reduced oocyte-sperm binding ability, and the number of cortical granules in mouse oocyte cortex. Taken together, this study demonstrated that VCR could cause meiotic arrest and poor quality of mouse oocyte.
The ETV6::PDGFRB fusion gene is commonly reported in chronic myelomonocytic leukemia with eosinophilia, yet patients with ETV6::PDGFRB presenting myeloid and lymphoid neoplasms successively have not been reported. Here, we report the first case of a 35-year-old man with myeloid and lymphoid neoplasms harboring an ETV6::PDGFRB fusion gene who demonstrated poor response to imatinib. The patient was diagnosed with an ETV6::PDGFRB fusion gene myeloid neoplasm on initial diagnosis at our hospital. After 5 months of treatment with imatinib, he was diagnosed with T-cell lymphoblastic lymphoma. ETV6::PDGFRB turned negative after increasing the dose of imatinib, but enlarged superficial lymph nodes reappeared the following year. Notably, the patient exhibited a worse response to imatinib treatment. This study describes this rare case and speculates on a possible mechanism.
Antibiotic contamination in drinking water has attracted widespread attention. The pollution condition of six macrolide antibiotics (erythromycin-H2[KG-*2/5]O, clarithromycin, oleandomycin, roxithromycin, leucomycin, and tylosin) in two drinking water treatment plants was monitored, and the reaction mechanism of tylosin, a typical macrolide antibiotic, during chlorination disinfection treatment was investigated. The results showed that the six macrolide antibiotics can be widely detected in the drinking water treatment processes; however, their concentrations were generally very low. The concentrations of macrolide antibiotics in the influents and effluents ranged from 0.18 ng·L-1 to 3.97 ng·L-1 and 0.02 ng·L-1 to 1.91 ng·L-1, respectively. The removal rates of the six macrolides in the drinking water treatment were different, ranging from 18% (oleandomycin) to 100% (erythromycin- H2[KG-*2/5]O). The degradation of the six macrolides during chlorination was slow and greatly affected by water quality parameters. The chlorination degradation of tylosin followed the second-order reaction kinetic mode, with the kinetic rate constant of 0.77 L·(mol·s)-1 at pH 7.0. Nine chlorination degradation products of tylosin were detected, and the reaction pathways primarily included tertiary amine hydroxylation, aromatic oxidation, and epoxy addition.
Drinking Water , Tylosin , Halogenation , Anti-Bacterial Agents , Macrolides , Erythromycin , Oleandomycin
BACKGROUND: Various studies have highlighted the significance of miR-125b-5p in tumour chemotherapy resistance; However, whether miR-125b-5p is associated with all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukemia (APL) has not been reported. METHODS: Drug-resistance-related factors in APL were predicted using the DRESIS database. The expression levels of miR-125b-5p in ATRA-sensitive and ATRA-resistant APL cells were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A nitrotetrazolium blue (NBT) reduction assay and flow cytometry (FCM) were used to detect the effect of miR-125b-5p on ATRA resistance in APL cells. An APL xenograft tumour mouse model was established to determine the effect of miR-125b-5p on ATRA resistance. A dual-luciferase gene reporter assay, qRT-PCR, and western blotting verified the regulation by miR-125b-5p of its target gene, MAPK1, and the MAPK1 downstream factor, C/EBPα. An NBT reduction assay and FCM were used to detect the effect of C/EBPα on ATRA resistance in APL cells. Western blotting and qRT-PCR were used to assess the regulation of miR-125b-5p and MAPK1 by C/EBPα. RESULTS: miR-125b-5p expression levels were dramatically increased in ATRA-resistant APL cells. Both in vitro and in vivo experiments revealed that miR-125b-5p overexpression enhanced ATRA resistance in APL. miR-125b-5p promoted ATRA resistance by sponging MAPK1. C/EBPα was negatively regulated by miR-125b-5p, which in addition, regulated ATRA resistance in APL cells. C/EBPα also regulated the miR-125b-5p-MAPK1 axis. CONCLUSION: The findings of this study indicate that the miR-125b-5p-MAPK1-C/EBPα feedback loop regulated ATRA resistance in APL. Thus, miR-125b-5p may be a promising target for treating ATRA resistance in APL.
CRISPR/Cas systems have found widespread applications in gene editing due to their high accuracy, high programmability, ease of use, and affordability. Benefiting from the cleavage properties (trans- or cis-) of Cas enzymes, the scope of CRISPR/Cas systems has expanded beyond gene editing and they have been utilized in various fields, particularly in live-cell imaging and bioanalysis. In this review, we summarize some fundamental working mechanisms and concepts of the CRISPR/Cas systems, describe the recent advances and design principles of CRISPR/Cas mediated techniques employed in live-cell imaging and bioanalysis, highlight the main applications in the imaging and biosensing of a wide range of molecular targets, and discuss the challenges and prospects of CRISPR/Cas systems in live-cell imaging and biosensing. By illustrating the imaging and bio-sensing processes, we hope this review will guide the best use of the CRISPR/Cas in imaging and quantifying biological and clinical elements and inspire new ideas for better tool design in live-cell imaging and bioanalysis.
CRISPR-Cas Systems , Diagnostic Imaging , CRISPR-Cas Systems/genetics , Gene Editing
Background: Multidrug-resistant (MDR) bacterial infection causes difficulty in the therapy of peritoneal dialysis-associated peritonitis (PDAP); however, there are few studies on multidrug-resistant organism (MDRO)-PDAP. In view of growing concerns about MDRO-PDAP, the aim of this study was to investigate the clinical features, risk factors of treatment failure, and causative pathogens of MDRO-PDAP. Methods: In total, 318 patients who underwent PD between 2013 and 2019 were included in this multicenter retrospective study. Clinical features, patient outcomes, factors related to treatment failure, and microbiological profiles associated with MDRO-PDAP were analyzed and risk factors for treatment failure associated with MDR-Escherichia coli (E. coli) were further discussed. Results: Of 1,155 peritonitis episodes, 146 eligible episodes of MDRO-PDAP, which occurred in 87 patients, were screened. There was no significant difference in the composition ratio of MDRO-PDAP between 2013-2016 and 2017-2019 (p > 0.05). E. coli was the most prevalent MDRO-PDAP isolate, with high sensitivity to meropenem (96.0%) and piperacillin/tazobactam (89.1%). Staphylococcus aureus was the second most common isolate and was susceptible to vancomycin (100%) and linezolid (100%). Compared to non-multidrug-resistant organism-PDAP, MDRO-PDAP was associated with a lower cure rate (66.4% vs. 85.5%), higher relapse rate (16.4% vs. 8.0%), and higher treatment failure rate (17.1% vs.6.5%). Dialysis age [odds ratio (OR): 1.034, 95% confidence interval (CI): 1.016-1.052, p < 0.001] and >2 previous peritonitis episodes (OR: 3.400, 95% CI: 1.014-11.400, p = 0.047) were independently associated with treatment failure. Furthermore, longer dialysis age (OR: 1.033, 95% CI: 1.003-1.064, p = 0.031) and lower blood albumin level (OR: 0.834, 95% CI: 0.700-0.993, p = 0.041) increased the risk of therapeutic failure for MDR-E. coli infection. Conclusion: The proportion of MDRO-PDAP has remained high in recent years. MDRO infection is more likely to result in worse outcomes. Dialysis age and previous multiple peritonitis infections were significantly associated with treatment failure. Treatment should be promptly individualized based on local empirical antibiotic and drug sensitivity analyses.
Aristolochic acid I (AAI) can cause nephrotoxicity and is characterized by interstitial fibrosis. The C3a/C3aR axis of macrophages and matrix metalloproteinase-9 (MMP-9) play important roles in fibrosis, but whether they are involved in AAI-induced renal interstitial fibrosis and are related remains to be elucidated. In this study, we investigated whether C3a/C3aR axis of macrophages promotes renal interstitial fibrosis by regulating MMP-9 in aristolochic acid nephropathy (AAN). Intraperitoneal injection of AAI for 28 days successfully induced AAN in C57bl/6 mice. The content of C3a in the kidney of AAN mice was increased, and there was a significant distribution of macrophages in the renal tubules. The same results were observed in the in vitro experiment. We also explored the role and mechanism of macrophages after AAI administration in the epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells (RTECs) and found that AAI could activate the C3a/C3aR axis of macrophages to upregulate p65 expression in macrophages. p65 upregulated MMP-9 expression in macrophages not only directly but also by promoting the secretion if interleukin-6 by macrophages and then activating STAT3 in RTECs. The upregulation of MMP-9 expression could promote the EMT of RTECs. Taken together, our study demonstrated that the AAI-activated the C3a/C3aR axis of macrophages, which induced MMP-9 production, was one of the causes of renal interstitial fibrosis. Therefore, targeting the C3a/C3aR axis of macrophages is an effective therapeutic strategy for the prevention and treatment of renal interstitial fibrosis in AAN.
Aristolochic Acids , Kidney Diseases , Mice , Animals , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Kidney Diseases/pathology , Kidney Tubules/metabolism , Macrophages/metabolism , Fibrosis , Aristolochic Acids/toxicity
In situ liquid cell electron microscopy (LC-EM) is a powerful platform for real time nanoscale imaging of liquid systems. In situ liquid cell scanning electron microscopy (LC-SEM) as a relatively low cost and potentially more convenient characterization method, has not been as widely used as compared to in situ liquid cell transmission electron microscopy (LC-TEM). This paper reports a real time high resolution and comprehensive characterization of Au nanoparticles (NPs) and nanoparticle clusters (NPCs), which are surface-decorated with cetyltrimethylammonium bromide (CTAB), in an oleic acid (OA) emulsion system with LC-SEM. Single NP resolution images are routinely collected with both secondary electron (SE) and backscattered electron (BSE) imaging modes, with different SEM systems. Energy dispersive spectroscopy (EDS) mapping data clearly demonstrates the single particle level chemical element distributions, particle stacking structure, as well as the preferred distribution of OA molecules on the Au particle surfaces. Moreover, both liquid droplet growth and particle motions are observed with LC-SEM, among which, ways for faster tracking the single particle level dynamic motion behavior of Au NPs and NPCs are explored. We expect that our work will bring new insight of high resolution and fast analysis in a broad range of materials in liquid with LC-SEM.
Protecting wheat yield is a top priority in agricultural production, and one of the important measures to preserve yield is the control of wheat diseases. With the maturity of computer vision technology, more possibilities have been provided to achieve plant disease detection. In this study, we propose the position attention block, which can effectively extract the position information from the feature map and construct the attention map to improve the feature extraction ability of the model for the region of interest. For training, we use transfer learning to improve the training speed of the model. In the experiment, ResNet built on positional attention blocks achieves 96.4% accuracy, which is much higher compared to other comparable models. Afterward, we optimized the undesirable detection class and validated its generalization performance on an open-source dataset.
Protecting crop yields is the most important aspect of agricultural production, and one of the important measures in preserving yields is the control of crop pests and diseases; therefore, the identification of crop pests and diseases is of irreplaceable importance. In recent years, with the maturity of computer vision technology, more possibilities have been provided for implementing plant disease detection. However, although deep learning methods are widely used in various computer vision tasks, there are still limitations and obstacles in practical applications. Traditional deep learning-based algorithms have some drawbacks in this research area: (1) Recognition accuracy and computational speed cannot be combined. (2) Different pest and disease features interfere with each other and reduce the accuracy of pest and disease diagnosis. (3) Most of the existing researches focus on the recognition efficiency and ignore the inference efficiency, which limits the practical production application. In this study, an integrated model integrating single-stage and two-stage target detection networks is proposed. The single-stage network is based on the YOLO network, and its internal structure is optimized; the two-stage network is based on the Faster-RCNN, and the target frame size is first clustered using a clustering algorithm in the candidate frame generation stage to improve the detection of small targets. Afterwards, the two models are integrated to perform the inference task. For training, we use transfer learning to improve the model training speed. Finally, among the 37 pests and 8 diseases detected, this model achieves 85.2% mAP, which is much higher than other comparative models. After that, we optimize the model for the poor detection categories and verify the generalization performance on open source datasets. In addition, in order to quickly apply this method to real-world scenarios, we developed an application embedded in this model for the mobile platform and put the model into practical agricultural use.
BACKGROUND: Several elderly patients with end-stage renal disease (ESRD) had to undergo urgent-start peritoneal dialysis (USPD). This study aimed to determine whether break-in period (BI) within 24 h was feasible in elderly patients undergoing USPD. METHODS: Patients with ESRD who underwent PD at five hospitals were screened. Patients were divided into the BI ≤24 h and >24 h groups. Complications were compared between the two groups. Multivariate logistic regression model was used to determine whether BI ≤24 h was associated with complications. RESULTS: A total of 175 elderly patients were included: BI ≤24 h group, 78; and BI >24 h group, 97. There was no significant difference in the rate of complications between the two groups (all p > 0.05). Furthermore, BI ≤24 h was not an independent risk factor for complications (all p > 0.05). CONCLUSIONS: Starting PD within 24 h after PD catheter insertion was feasible in elderly ESRD patients.
Kidney Failure, Chronic , Peritoneal Dialysis , Humans , Aged , Retrospective Studies , Time Factors , Kidney Failure, Chronic/therapy , Catheterization
Nickel resources are abundant in the world, and the application of nickel in production and life is more and more extensive. However, excessive nickel entering the environment will not only cause environmental pollution but also seriously endanger plants, animals and human health. Nickel compounds are carcinogenic and have been classified as a class 1 carcinogen. Nickel mainly exists in the form of divalent ions in the environment. However, there are few simple and effective methods for the detection of nickel ions, and these methods still have certain limitations. At present, the mechanisms of nickel influence in organisms are also unclear. Therefore, we constructed a ratiometric fluorescent probe Ra-Ni, which can achieve its own self-calibration and avoid the interference of other factors, thereby realizing the specific identification of nickel ions. The probe can detect nickel ions sensitively with a detection limit as low as 26.2 nM and can respond in a short time (< 2 min), which proves the great potential of the probe in the detection of nickel ions. At the same time, Ra-Ni has also been successfully used for imaging nickel ions in living cells and zebrafish, providing an effective tool for the study of physiological and pathological processes. The detection effect of nickel ions in actual water sample is also satisfactory, which further demonstrates the practicability of Ra-Ni in environmental applications.
Fluorescent Dyes , Nickel , Animals , Ions , Zebrafish
OBJECTIVE: To prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection. METHODS: DOX-loaded PELA staple fibers (FDOX) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of FDOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (GCA4P/FDOX). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of GCA4P/FDOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments. RESULTS: The average length of FDOX was 4.0±1.3 µm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 â, the composite rapidly solidified to form a gel in vitro. Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with GCA4P/FDOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm3 in GCA4P/FDOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G4A4P/FDOX. CONCLUSION: As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.
Breast Neoplasms , Hydrogels , Animals , Breast Neoplasms/drug therapy , Cell Line, Tumor , Delayed-Action Preparations/therapeutic use , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Female , Heterografts , Humans , Hydrogels/therapeutic use , Mice , Mice, Inbred BALB C , Phosphates
