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2.
Sci Rep ; 14(1): 11610, 2024 05 21.
Article in English | MEDLINE | ID: mdl-38773218

ABSTRACT

Although endoscopic necrosectomy (EN) is more frequently used to manage walled-off necrosis (WON), there is still debate over how much time should pass between the initial stent placement and the first necrosectomy. This study aims to determine the effect of performing EN within different timings after placing the initial stent on clinical outcomes for WON. A retrospective study on infected WON patients compared an early necrosectomy within one week after the initial stent placement with a necrosectomy that was postponed after a week. The primary outcomes compared the rate of clinical success and the need for additional intervention after EN to achieve WON resolution. 77 patients were divided into early and postponed necrosectomy groups. The complete resolution of WON within six months of follow-up was attained in 73.7% and 74.3% of patients in both the early and postponed groups. The early group tended to a greater need for additional intervention after EN (26.8% early necrosectomy vs. 8.3% postponed necrosectomy, P = 0.036). Our study does not demonstrate that early necrosectomy is superior to postponed necrosectomy in terms of clinical success rate, total count of necrosectomy procedures, procedure-related complications, length of hospitalization and prognosis. Conversely, patients in the postponed group received fewer additional interventions.


Subject(s)
Pancreatitis, Acute Necrotizing , Humans , Male , Female , Middle Aged , Retrospective Studies , Pancreatitis, Acute Necrotizing/surgery , Pancreatitis, Acute Necrotizing/pathology , Adult , Aged , Treatment Outcome , Endoscopy/methods , Stents/adverse effects , Necrosis , Drainage/methods
3.
World J Surg Oncol ; 22(1): 107, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38644507

ABSTRACT

BACKGROUND: Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. PATIENTS AND METHODS: The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. RESULTS: In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P < 0.05). Compared to the TD-negative group, the TD-positive group showed significantly poorer CSS (the training cohort: HR, 1.87; 95% CI, 1.52-2.31; the validation cohort: HR, 2.43; 95% CI, 1.55-3.81; all P values < 0.001). This association was significant in stage III but not in stage IV. In the multivariate model, after adjusting for covariates, TD maintained an independent prognostic value (P < 0.05). A nomogram model including TD, N stage, T stage, TNM stage, CEA, and chemotherapy was constructed. Through internal and external validation, the model demonstrated good calibration and accuracy. Further survival curve analysis based on individual scores from the model showed good discrimination. CONCLUSION: TD positivity is an independent factor of poor prognosis in colorectal SRCC patients, and it is more effective to predict the prognosis of colorectal SRCC by building a model with TD and other clinically related variables.


Subject(s)
Carcinoma, Signet Ring Cell , Colorectal Neoplasms , Neoplasm Staging , Nomograms , SEER Program , Humans , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/surgery , Carcinoma, Signet Ring Cell/mortality , Female , Male , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Middle Aged , Prognosis , Survival Rate , Follow-Up Studies , Aged , Retrospective Studies , China/epidemiology , Neoplasm Invasiveness , Adult
4.
Article in English | MEDLINE | ID: mdl-38597290

ABSTRACT

Alleviating the injury of type II alveolar epithelial cells (AEC 2s) and inhibiting the activation and differentiation of fibroblasts are significant for improving the therapeutic effect of idiopathic pulmonary fibrosis (IPF). To this aim, ionizable liposome nanoparticles (ASNPs) coloaded with antioxidant drug astaxanthin (AST) and small interfering RNA targeting transforming growth factor ß1 (siTGF-ß1) were developed for enhanced IPF therapy. ASNPs showed high loading and intracellular delivery efficiency for AST and siTGF-ß1. After the injection of ASNPs in an IPF mice model, the loaded AST largely scavenged reactive oxygen species (ROS) in the diseased lung to reduce AEC2 apoptosis, thereby ensuring the integrity of the alveolar epithelium. Meanwhile, siTGF-ß1, delivered by ASNPs, significantly silenced the expression of TGF-ß1 in fibroblasts, inhibiting the differentiation of fibroblasts into myofibroblasts as well as reducing the excessive deposition of extracellular matrix (ECM). The combined use of the two drugs exhibited an excellent synergistic antifibrotic effect and was conducive to minimizing alveolar epithelial damage. This work provides a codelivery strategy of AST and siTGF-ß1, which shows great promise for the treatment of IPF by simultaneously reducing alveolar epithelial damage and inhibiting fibroblast activation.

5.
Inflamm Bowel Dis ; 29(12): 1929-1940, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-37335900

ABSTRACT

BACKGROUND: Honokiol (HKL), a natural extract of the bark of the magnolia tree and an activator of the mitochondrial protein sirtuin-3 (SIRT3), has been proposed to possess anti-inflammatory effects. This study investigated the inhibitory effects of HKL on T helper (Th) 17 cell differentiation in colitis. METHODS: Serum and biopsies from 20 participants with ulcerative colitis (UC) and 18 healthy volunteers were collected for the test of serum cytokines, flow cytometry analysis (FACS), and relative messenger RNA (mRNA) levels of T cell subsets, as well as the expression of SIRT3 and phosphorylated signal transducer and activator of transcription/retinoic acid-related orphan nuclear receptor γt (p-STAT3/RORγt) signal pathway in colon tissues. In vitro, naïve clusters of differentiation (CD) 4 + T cells isolated from the mouse spleen differentiated to subsets including Th1, Th2, Th17, and regulatory T (Treg) cells. Peripheral blood monocytes (PBMCs) from healthy volunteers were induced to the polarization of Th17 cells. After HKL treatment, changes in T cell subsets, related cytokines, and transcription factors were measured. The dextran sulfate sodium (DSS)-induced colitis and interleukin (IL)-10-deficient mice were intraperitoneally injected with HKL. These experiments were conducted to study the effect of HKL on the development, cytokines, and expression of signaling pathway proteins in colitis. RESULTS: Patients with UC had higher serum IL-17 and a higher proportion of Th17 differentiation in blood compared with healthy participants; while IL-10 level and the proportion of Treg cells were lower. Higher relative mRNA levels of RORγt and a lower SIRT3 expression in colon tissues were observed. In vitro, HKL had little effect on the differentiation of naïve CD4+ T cells to Th1, Th2, or Treg cells, but it downregulated IL-17 levels and the Th17 cell ratio in CD4+ T cells from the mouse spleen and human PBMCs under Th17 polarization. Even with a STAT3 activator, HKL still significantly inhibited IL-17 levels. In DSS-induced colitis mice and IL-10 deficient mice treated with HKL, the length of the colon, weight loss, disease activity index, and histopathological scores were improved, IL-17 and IL-21 levels, and the proportion of Th17 cells were decreased. Sirtuin-3 expression was increased, whereas STAT3 phosphorylation and RORγt expression were inhibited in the colon tissue of mice after HKL treatment. CONCLUSIONS: Our study demonstrated that HKL could partially protect against colitis by regulating Th17 differentiation through activating SIRT3, leading to inhibition of the STAT3/RORγt signaling pathway. These results provide new insights into the protective effects of HKL against colitis and may facilitate the research of new drugs for inflammatory bowel disease.


Subject(s)
Colitis, Ulcerative , Colitis , Sirtuin 3 , Humans , Animals , Mice , Interleukin-17/metabolism , Interleukin-10/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Th17 Cells , Sirtuin 3/metabolism , Sirtuin 3/pharmacology , Sirtuin 3/therapeutic use , Colitis/chemically induced , Colitis/drug therapy , Colitis/pathology , Colitis, Ulcerative/pathology , T-Lymphocytes, Regulatory/metabolism , Cytokines/metabolism , Cell Differentiation , RNA, Messenger/metabolism , Dextran Sulfate/adverse effects
7.
J Control Release ; 357: 249-263, 2023 05.
Article in English | MEDLINE | ID: mdl-37011837

ABSTRACT

Mesenchymal stem cell (MSC) transplantation is emerging as a promising approach in the treatment of idiopathic pulmonary fibrosis (IPF), while it is still impeded by several challenges, including unsatisfactory treatment outcomes due to the poor survival of transplanted MSCs, and the lack of non-invasive and long-term imaging modality for tracking the behavior of MSCs. Herein, copper-based nanozyme (CuxO NPs) and gold nanoparticles (Au NPs) were encapsulated in oxidation-sensitive dextran (Oxi-Dex), a dextran derivative with reactive oxygen species (ROS)-responsiveness, forming a kind of novel nanocomposites (assigned as RSNPs) to act as ROS scavengers and computer tomography (CT) imaging tracers. After being internalized by MSCs, RSNPs enabled continuous CT imaging tracking of the transplanted MSCs for 21 days in IPF treatment, obtaining the location and distribution of the transplanted MSCs. Once MSCs were attacked by oxidative stress, the intracellular RSNPs could activate ROS clearance on demand by releasing CuxO NPs, thereby enhancing the therapeutic efficacy against IPF by improving cell survival. Taken together, a novel multifunctional RSNP was fabricated to label MSCs for CT imaging tracking and clearing superfluous ROS, presenting a promising high-efficient IPF therapy.


Subject(s)
Idiopathic Pulmonary Fibrosis , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Metal Nanoparticles , Nanocomposites , Humans , Antioxidants , Reactive Oxygen Species , Gold , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/therapy , Tomography , Tomography, X-Ray Computed , Mesenchymal Stem Cell Transplantation/methods
8.
ACS Nano ; 17(7): 6387-6399, 2023 04 11.
Article in English | MEDLINE | ID: mdl-36946383

ABSTRACT

Mesenchymal stem cell (MSC) therapy has been proven to be a potentially effective approach for idiopathic pulmonary fibrosis (IPF) treatment. However, this strategy is currently limited by the poor curative effect and an insufficient comprehension of the in vivo condition of the transplanted MSCs in the remedy of IPF. To address these issues, herein, a nanosystem composed of Janus Au/mesoporous silica core/shell nanoparticles (Janus NPs) is designed for effective therapeutic and real-time tracing of MSCs in MSC-based IPF therapy. The Janus NPs consist of a Au core and a pirfenidone (PFD)-loaded mesoporous silica shell asymmetrically decorated with two targeting moieties: one is reactive oxygen species (ROS)-sensitive thioketal grafted methoxy poly(ethylene glycol) (mPEG-TK), and the other is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE). The asymmetric decoration on each side of the particle allows long-term anchoring of the Janus NPs on the cell membrane to facilitate the responsive release of PFD in the ROS environment of the fibrotic lung, thereby enhancing the therapeutic efficacy of the transplanted MSCs by improving the microenvironment. Following drug release, the Janus NPs quickly enter into MSCs, achieving long-term computed tomography (CT) imaging tracing of MSCs in IPF model mice for an in-depth comprehension of the cell therapy mechanism. Overall, this work reports on Janus Au/PFD-loaded mesoporous silica core/shell NPs that combine the drug delivery and imaging tracking of MSCs, which may provide a strategy for the stem cell-based treatment of IPF.


Subject(s)
Nanoparticles , Pulmonary Fibrosis , Mice , Animals , Reactive Oxygen Species/metabolism , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/drug therapy , Silicon Dioxide , Tomography, X-Ray Computed
9.
J Clin Lab Anal ; 36(10): e24699, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36106389

ABSTRACT

BACKGROUND: The etiology of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is not completely clear, but its pathogenesis is closely related to T helper 17 (Th17) cells. Several histone deacetylase (HDAC) inhibitors have been shown to exert potent anti-inflammatory effects and modulate Th17 cell polarization. Owing to the large variety and broad expression of HDACs, finding specific therapeutic targets for IBD is of clinical importance. METHODS: The proportions of Th17 cells and interleukin (IL)-17A produced between patients with UC and healthy volunteers were compared. The differentiation of human peripheral blood mononuclear cells (PBMCs) into Th17 cells was induced in vitro. Differentiated Th17 cells were treated with RGFP109 (RG), a selective inhibitor of HDAC1 and 3, to observe its effects on these cells. Subsequently, colitis was induced in mice and treated with RG. The proportion of Th17 cells, the severity of colitis in mice, and colon histopathology and immunohistochemistry were evaluated respectively. RESULTS: The proportion of Th17 cells and IL-17A production was significantly increased in patients with UC than in healthy individuals. RG inhibited the differentiation of human PBMCs into Th17 cells and reduced IL-17A secretion in vitro. RG-treated colitis mice had a lower Th17 ratio, mild colon inflammation, and decreased expression of HDAC1 and 3 in the colon. CONCLUSIONS: HDAC1 and 3 inhibitors can modulate the differentiation of inflammatory Th17 cells, downregulate IL-17A levels, and exert anti-inflammatory effects in experimental colitis mice, indicating that HDAC1 and 3 may be potential therapeutic targets for patients with IBD.


Subject(s)
Colitis, Ulcerative , Colitis , Inflammatory Bowel Diseases , Animals , Anti-Inflammatory Agents/metabolism , Cell Differentiation , Colitis/drug therapy , Colitis/metabolism , Colitis/pathology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Histone Deacetylase 1/metabolism , Histone Deacetylase 1/pharmacology , Humans , Inflammation/pathology , Interleukin-17 , Leukocytes, Mononuclear/metabolism , Mice , Th17 Cells/pathology
10.
Biomaterials ; 288: 121731, 2022 09.
Article in English | MEDLINE | ID: mdl-35970616

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) therapy has always been a big and long-standing challenge in clinical practice due to the lack of miraculous medicine. Mesenchymal stem cells (MSCs)-based therapy has recently emerged as a promising candidate for redefining IPF therapy. Enhancing the therapeutic efficacy of MSCs and understanding of their growth, migration and differentiation in harsh lung microenviroments are two keys to improving the stem cell-based IPF treatment. Herein, a non-viral dual-functional nanocarrier is fabricated by a one-pot approach, using protamine sulfate stabilized Au nanoparticles (AuPS), to genetically engineer MSCs for simultaneous IPF treatment and monitoring the biological behavior of the MSCs. AuPS exhibits superior cellular uptake ability, which results in efficient genetic engineering of MSCs to overexpress hepatocyte growth factor for enhanced IPF therapy. In parallel, the intracellular accumulation of AuPS improves the CT imaging contrast of MSCs, allowing visual tracking of the therapeutic engineered MSCs up to 48 days. Overall, this work has described for the first time a novel strategy for enhanced therapeutic efficacy and long-term CT imaging tracking of transplanted MSCs in IPF therapy, providing great prospect for stem cell therapy of lung disease.


Subject(s)
Idiopathic Pulmonary Fibrosis , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Metal Nanoparticles , Gold/metabolism , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/metabolism , Idiopathic Pulmonary Fibrosis/therapy , Mesenchymal Stem Cell Transplantation/methods , Tomography, X-Ray Computed
11.
Biomater Adv ; 137: 212869, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35929245

ABSTRACT

Diabetic chronic wound healing is a critical clinical challenge due to the particularity of wound microenvironment, including hyperglycemia, excessive oxidative stress, hypoxia, and bacterial infection. Herein, we developed a multifunctional self-healing hydrogel dressing (defined as OHCN) to regulate the complex microenvironment of wound for accelerative diabetic wound repair. The OHCN hydrogel dressing was constructed by integrating Au-Pt alloy nanoparticles into a hydrogel (OHC) that formed through Schiff-base reaction between oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS). The dynamic cross-linking of OHA and antibacterial CMCS imparted the OHCN hydrogel dressing with excellent antibacterial and self-healing properties. Meanwhile, Au-Pt alloy nanoparticles endowed the OHCN hydrogel dressing with the functions of lowering blood glucose, alleviating oxidative damage, and providing O2 by simulating glucose oxidase and catalase. Through a synergistic combination of OHC hydrogel and Au-Pt alloy nanoparticles, the resulted OHCN hydrogel dressing significantly ameliorated the pathological microenvironment and accelerated the healing rate of diabetic wound. The proposed nanozyme-decorated multifunctional hydrogel offers an efficient strategy for the improved management of diabetic chronic wound.


Subject(s)
Diabetes Mellitus , Hydrogels , Alloys , Anti-Bacterial Agents , Bandages , Humans , Hydrogels/pharmacology , Wound Healing
12.
J Biomed Nanotechnol ; 18(4): 1044-1051, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35854460

ABSTRACT

Mesenchymal stem cells (MSCs) have demonstrated great potential for tissue engineering and regenerative medicine applications. Noninvasive and real-term tracking of transplanted MSCs in vivo is crucial for studying the distribution and migration of MSCs, and their role in tissue injury repair. This study reports on the use of ferrimagnetic vortex iron oxide (FVIO) nanorings modified with anti-human integrin ß1 for specific recognition and magnetic resonance imaging (MRI) tracking of human MSCs (hMSCs). Integrin ß1 is highly expressed at all stem cell proliferation and differentiation stages. Therefore, the anti-integrin ß1 antibody (Ab) introduced in FVIO targets integrin ß1, thus enabling FVIO to target stem cells at any stage. This is unlike the traditional MRI-based monitoring of transplanted stem cells, which usually requires pre-labeling the stem cells with tracers before injection. Because of the ability to recognize hMSCs, the Ab-modified FVIO nanotracers (FVIO-Ab) have the advantage of not requiring pre-labeling before stem cell transplantation. Furthermore, the FVIO-Ab nanotracers have high T*2 contrast resulting from the unique magnetic properties of FVIO which can improve the MRI tracking efficiency of stem cells. This work may provide a new way for stem cell labeling and in vivo MRI tracking, thus reducing the risks associated with stem cell transplantation and promoting clinical translation.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Cell Tracking/methods , Ferric Compounds , Humans , Integrin beta1 , Magnetic Resonance Imaging/methods
13.
Comput Intell Neurosci ; 2022: 6836524, 2022.
Article in English | MEDLINE | ID: mdl-35832240

ABSTRACT

The establishment of enterprise target inventory is directly related to the forecast of drug sales volume. Accurate sales forecasting can help businesses not only set accurate target inventory but also avoid inventory backlogs and shortages. In this paper, NN technology is used to forecast sales and is optimized using the PSO algorithm, resulting in the creation of a drug sale forecast model. The model optimizes the weights and thresholds of NN using the improved PSO optimization algorithm and predicts the periodic components based on time correlation characteristics, effectively describing the trend growth and seasonal fluctuations of sales forecast data. Furthermore, the model in this paper has been creatively improved according to the needs of practical application, which has improved the shortcomings of traditional NN, such as long training time, slow convergence speed, and ease to fall into local minima, to improve performance and quality, and has received positive results in application. The experimental results show that this model has a prediction accuracy of 96.14 percent, which is 12.78 percent higher than the traditional BP model. The optimized model can be used to forecast drug sales in a practical and feasible way.


Subject(s)
Algorithms , Neural Networks, Computer , Forecasting
14.
Nanoscale ; 14(13): 5227-5238, 2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35315848

ABSTRACT

Mesenchymal stem cells (MSCs) have showed promising effects in the treatment of liver fibrosis. Long-term and noninvasive in vivo tracking of transplanted MSCs is essential for understanding the therapeutic mechanism of MSCs during the therapy of liver fibrosis. In this study, we report the development of a ferrimagnetic vortex iron oxide nanoring (FVIO)-based nanotracer for the long-term visualization of transplanted human MSCs (hMSCs) by magnetic resonance imaging (MRI). The FVIOs were prepared by a hydrothermal reaction followed by hydrogen reduction. To endow the FVIOs with biocompatibility, polyethylene glycol amine (mPEG-NH2) was covalently coupled on the surface of FVIOs, forming FVIO@PEG nanotracers with high contrast enhancement and intracellular uptake. The hMSCs labeled with FVIO@PEG nanotracers exhibited enhanced MRI contrast than those labeled with a commercial contrast agent, and could be continuously monitored by MRI in liver fibrosis mice for 28 days after transplantation, clearly clarifying the migration behavior of hMSCs in vivo. Moreover, we explored the therapeutic mechanism of the FVIO@PEG labeled hMSCs in the amelioration of liver fibrosis, including the reduction in inflammation and oxidative stress, the inhibition of hepatic fibrosis-caused histopathological damage, as well as the down-regulation of the expression of relevant cytokines. The results obtained in this work may deepen our understanding of the behavior and role of hMSCs in the treatment of liver fibrosis, which is key to the clinical application of stem cells in the therapy of liver diseases.


Subject(s)
Mesenchymal Stem Cells , Animals , Ferric Compounds , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/therapy , Magnetic Resonance Imaging/methods , Mice
15.
Nanomedicine ; 41: 102517, 2022 04.
Article in English | MEDLINE | ID: mdl-35032629

ABSTRACT

Mesenchymal stem cells (MSCs) are promising in idiopathic pulmonary fibrosis (IPF) therapy. However, low survival rate and ambiguous behavior of MSCs after transplantation impede their clinical translation. To this end, we have developed a new strategy to improve the survival rate and monitor the behavior of the transplanted MSCs simultaneously. In our strategy, nintedanib, a tyrosine kinase inhibitor, is employed to protect the human MSCs (hMSCs) from excessive oxidative stress responses and inflammatory environment in the damaged lung. Moreover, by labeling of the transplanted hMSCs with a computed tomography (CT) nanotracer, Au nanoparticles functionalized with polyethylenimine (PEI) and polyethylene glycol (PEG) (Au@PEI@PEG), in combination with red-emitting firefly luciferase (RfLuc), in vivo CT/bioluminescence (BL) dual-modal imaging tracking of the location, distribution, and survival of the transplanted hMSCs in presence of nintedanib were achieved, which facilitates the profound understanding of the role the stem cells play in IPF therapy.


Subject(s)
Idiopathic Pulmonary Fibrosis , Mesenchymal Stem Cells , Metal Nanoparticles , Gold , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/drug therapy , Indoles , Luciferases, Firefly , Metal Nanoparticles/therapeutic use , Polyethylene Glycols , Polyethyleneimine , Tomography, X-Ray Computed
16.
Biomater Sci ; 10(2): 368-375, 2022 Jan 18.
Article in English | MEDLINE | ID: mdl-34897301

ABSTRACT

The identification of paracrine factors secreted by transplanted mesenchymal stem cells (MSCs) during the treatment of idiopathic pulmonary fibrosis (IPF) is essential for understanding the role of MSCs in therapy. Herein, we report a facile and efficient strategy for in vivo tracking the secretion of hepatocyte growth factor (HGF) in MSCs during IPF therapy. In our strategy, a novel nanoflare tracer consisting of gold nanoparticles (AuNPs), complementary sequences and dye-labeled recognition sequences is developed. Briefly, the AuNPs are functionalized with oligonucleotide complementary sequences hybridized to the organic dye-labeled recognition sequences, where the organic fluorophores are in close proximity to the AuNPs. In the absence of targets, the dye and AuNPs are separated from each other, inducing the quenching of the fluorescence signal. However, in the presence of targets, the recognition sequences gradually fall off from the AuNPs, causing the fluorescence signal to rise. In brief, in vivo monitoring of the dynamic expression of HGF mRNA in transplanted MSCs during IPF therapy in the current work may provide new insight into the paracrine process of the transplanted MSCs, thereby advancing the MSC-based IPF therapy toward clinical applications.


Subject(s)
Mesenchymal Stem Cells , Metal Nanoparticles , Pulmonary Fibrosis , DNA , Gold , Hepatocyte Growth Factor/genetics , Humans
17.
J Mater Chem B ; 9(48): 10003-10014, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34874044

ABSTRACT

Injectable hydrogels have aroused ever-increasing interest for their cell/biomaterial delivery ability through minimally invasive procedures. Nevertheless, it is still a challenge to simply fabricate natural biopolymer-based injectable hydrogels possessing satisfactory mechanical properties, bioadhesion, and cell delivery ability. Herein, we describe a facile dual crosslinking (DC) strategy for preparing extracellular matrix (ECM) mimetic hydrogels with desirable comprehensive performance. The chondroitin sulfate (CS)- and gelatin (Gel)-based single crosslinked (SC) hydrogels were first developed via reversible borate ester bonds, and further strengthened through the Michael-addition crosslinking reaction or visible-light initiated photopolymerization with thiol-containing polyethylene glycol (PEG) crosslinkers. The dynamic SC hydrogels showed good injectability, pH-sensitive gel-sol transformation, and self-adhesion ability to various biological tissues such as skin, liver, and intervertebral disc. The mechanically tough DC hydrogels displayed tunable stiffness, and resilience to compression load (up to 90% strain) owing to the effective energy dissipation mechanism. The formed DC hydrogels after subcutaneous injection well integrated with surrounding tissues and exhibited fast self-recovery properties. Moreover, the photoencapsulation of human mesenchymal stem cells (hMSCs) within the developed DC hydrogels was achieved and has been proved to be biocompatible, highlighting the great potential of the photopolymerized DC hydrogels in cell delivery and three-dimensional (3D) cell culture. This biomimetic, mechanically resilient, adhesive, and cytocompatible injectable DC hydrogel could serve as a promising candidate for tissue engineering.


Subject(s)
Biocompatible Materials/chemistry , Cross-Linking Reagents/chemistry , Extracellular Matrix/chemistry , Hydrogels/chemistry , Tissue Engineering , Biocompatible Materials/chemical synthesis , Cells, Cultured , Cross-Linking Reagents/chemical synthesis , Humans , Hydrogels/chemical synthesis , Materials Testing , Polyethylene Glycols/chemistry , Stress, Mechanical , Sulfhydryl Compounds/chemistry , Tissue Adhesions
18.
Biomed Mater ; 16(6)2021 10 12.
Article in English | MEDLINE | ID: mdl-34571498

ABSTRACT

Oral insulin has been regarded as the best alternative to insulin injection in therapy of diabetes because of its convenience and painlessness. However, several obstacles in the gastrointestinal tract, such as gastric acid and enzyme, greatly reduce the bioavailability of oral insulin. Herein, we report design and preparation of poly (d, l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with 5ß-cholanic acid modified glycol chitosan (GC-CA) (GC-CA@PLGA NPs) to improve the oral delivery of insulin. The GC-CA@PLGA NPs with the size of (302.73 ± 5.13 nm) and zeta potential of (25.03 ± 0.31 mV) were synthesized using the double-emulsion method. The insulin-loading capacity and encapsulation efficiency were determined to be 5.77 ± 0.58% and 51.99 ± 5.27%, respectively. Compared with GC-modified PLGA NPs (GC@PLGA NPs) and bare PLGA NPs, the GC-CA@PLGA NPs showed excellent stability and uptake by Caco-2 cells after simulated gastric acid digestion. Further experiment suggests good biocompatibility of GC-CA@PLGA NPs, including hemolysis and cytotoxicity. Inin vivoexperiment, the insulin loaded in the GC-CA@PLGA NPs exhibited a long-term and stable release profile for lowering blood glucose and presented 30.43% bioavailability in oral administration. In brief, we have developed an efficient and safe drug delivery system, GC-CA@PLGA NPs, for significantly improved oral administration of insulin, which may find potential application in the treatment of diabetes.


Subject(s)
Chitosan , Nanoparticles , Caco-2 Cells , Cholic Acids , Drug Carriers , Humans , Insulin , Particle Size , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer
19.
Small ; 17(33): e2101861, 2021 08.
Article in English | MEDLINE | ID: mdl-34235846

ABSTRACT

Gold nanoparticles (AuNPs) pose a great challenge in the development of nanotracers that can self-adaptively alter their properties in response to certain cellular environments for long-term stem cell tracking. Herein, pH-sensitive Au nanotracers (CPP-PSD@Au) are fabricated by sequential coupling of AuNPs with sulfonamide-based polymer (PSD) and cell-penetrating peptide (CPP), which can be efficiently internalized by mesenchymal stem cells (MSCs) and undergo pH-induced self-assembly in endosomes, facilitating long-term computed tomography (CT) imaging tracking MSCs in a murine model of idiopathic pulmonary fibrosis (IPF). Using the CPP-PSD@Au, the transplanted MSCs for the first time can be monitored with CT imaging for up to 35 days after transplantation into the lung of IPF mice, clearly elucidating the migration process of MSCs in vivo. Moreover, we preliminarily explored the mechanism of the CPP-PSD@Au labeled MSCs in the alleviation of IPF, including recovery of alveolar integrity, decrease of collagen deposition, as well as down-regulation of relevant cytokine level. This work facilitates our understanding of the behavior and effect of MSCs in the therapy of IPF, thereby providing an important insight into the stem cell-based treatment of lung diseases.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Metal Nanoparticles , Pulmonary Fibrosis , Animals , Gold , Hydrogen-Ion Concentration , Mice , Tomography, X-Ray Computed
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