A systematic review and meta-analysis of the relative safety and efficacy of treating lower extremity deep vein thrombosis via pharmacomechanical thrombectomy and catheter-directed thrombolysis.

OBJECTIVE: To evaluate the safety and efficacy of pharmacomechanical thrombectomy and catheter-directed thrombolysis (CDT) as approaches to treating deep venous thrombosis of lower extremities (LEDVT). METHODS: The PubMed, Web of Science, Wanfang, Embase, Chinese Science and Technology Journal, Cochrane, and China National Knowledge Infrastructure (CNKI) databases were systematically searched for relevant articles published through October 2023, after which appropriate inclusion and exclusion criteria were used to screen out relevant articles. Review Manager 5.4.1 was used to extract key data from these studies, and pooled analyses were conducted based on mead difference (MD) or odds ratio (OR) values and corresponding 95% confidence interval (CI). Study quality was assessed with the Newcastle-Ottawa scale. TRIAL REGISTRATION: This study has been registered at INPLASY.COM (No. INPLASY2023100075). RESULTS: In total, 31 relevant studies enrolling 2413 patients were included in this meta-analysis, with 1184 and 1229 patients in the AngioJet and CDT groups, respectively. These analyses revealed that the AngioJet group exhibited significantly higher rates of early postoperative deep vein patency (MD = 7.73, 95% CI (3.29, 12.17), p = .0006) and affected limb symptom improvement (MD = 6.31, 95% CI (1.82,10.80), p = .006) relative to the CDT group, whereas no differences in grade II or III thrombus clearance rates (OR = 1.30, 95% CI (0.95, 1.77), p = .10) or changes in thigh circumference before and after treatment (MD = 0.01, 95% CI (-0.80, 0.83), p = .97) were observed. The AngioJet group also exhibited lower urokinase doses (MD = -145.33, 95% CI (-164.28,126.38), p < .00001), shorter thrombolysis time (MD = -2.35, 95% CI(-2.80, -1.90), p < .00001), a less prolonged hospital stay (MD = -3.13, 95% CI(-3.81, -2.45), p < .00001), lower rates of PTS incidence (OR = 0.56, 95% CI(0.36, 0.88), p = .01), and reduced complication rates (OR = 0.51, 95% CI(0.31, 0.83), p = .0007). CONCLUSION: Studies published to date suggest that relative to CDT treatment, pharmacomechanical thrombectomy is associated with improved thrombus clearance, fewer complications, and lower complication rates in LEDVT patients, underscoring the safety and efficacy of this therapeutic strategy.

Stent Insertion for Inoperable Hilar Cholangiocarcinoma: Comparison Between Unilateral Radioactive Stent and Bilateral Normal Stent.

OBJECTIVE: To comparatively analyze the clinical efficacy and safety of unilateral radioactive stent (RS) insertion versus bilateral normal stent (NS) insertion in patients with inoperable hilar cholangiocarcinoma (HC). PATIENTS AND METHODS: Patients with inoperable HC were treated in our hospital from January 2016 to December 2020. The treatment approach included the insertion of either unilateral RS or bilateral NS, evaluating the efficacy and safety of therapy in 2 distinct groups. RESULTS: A total of 58 individuals experienced the insertion of a unilateral RS, whereas 57 patients underwent the insertion of bilateral NS. No statistically significant difference between the unilateral RS and bilateral NS groups was seen in the technical success rates (98.3% vs 94.7%, P = 0.598) and clinical success rates (98.2% vs 100%, P = 0.514). While there is no statistically significant difference in the rates of stent restenosis (19.3% vs 9.3%, P = 0.132) between the two groups, the unilateral RS group demonstrated substantially longer stent patency (202 vs 119 d, P = 0.016) and overall survival (229 vs 122 d, P = 0.004) compared with the bilateral NS group. Moreover, 8 patients (14.0%) in the unilateral RS group and 14 patients (25.9%) in the bilateral NS group had postoperative complications with no significant difference ( P = 0.116). CONCLUSION: When inserting stents for inoperable HC, both unilateral RS and bilateral NS insertion procedures have demonstrated favorable therapeutic efficacy. Nevertheless, inserting a unilateral RS provided a longer duration of stent patency and overall survival than implantation of bilateral NS.

Radioactive Seed Strand Efficacy in Superior Vena Cava Stenting Due to Non-small-cell Lung Cancer Obstruction.

PURPOSE: This study aims to determine the clinical effectiveness of a stent with radioactive seed strand (RSS) inserted in patients with superior vena cava (SVC) obstruction (SVCO) secondary to non-small-cell lung cancer (NSCLC). METHODS: Between January 2013 and December 2019, 63 patients with SVCO related to NSCLC received stent implantation with (n = 30) or without (n = 33) RSS insertion at our center. The clinical efficacy, stent patency duration, and overall survival (OS) were compared between these two groups. RESULTS: Both groups achieved 100% clinical and technical success rates. There were no obstacles associated with the procedure performed for the patients. Two patients in the RSS group and 7 patients in the stent-alone group experienced stent re-stenosis. The rate of re-stenosis between the two groups was not significantly different (P = .099). Patients in the RSS group had significantly longer median patency than those in the stent-alone group (381 vs 309 days, P = .045). All patients died because of the development of tumors during the follow-up. Patients in the RSS group had a significantly longer median OS than those in the stent-alone group (229 vs 178 days, P = .026). During the follow-up, no patient in the RSS group suffered RSS migration or brachytherapy-related complications. CONCLUSION: For patients with SVCO secondary to NSCLC, a stent with RSS insertion is efficacious and safe, and it may improve stent patency and OS.

Thrombolysis Combined Therapy Using CuS@SiO2-PEG/uPA Nanoparticles.

Massive hemorrhage caused by the uncontrolled release of thrombolysis drugs is a key issue of thrombolysis therapy in clinical practice. In this study, we report a near-infrared (NIR) light-triggered drug delivery system, i.e., CuS@mSiO2-PEG (CSP) nanoparticles, for the loading of a thrombolytic drug (urokinase plasminogen activators, uPA). CSP nanoparticles with the CuS nanoparticles as photothermal agents and mesoporous SiO2 for the loading of uPA were synthesized using a facile hydrothermal method. The CSP core-shell nanoparticles were demonstrated to possess excellent photothermal performance, exhibiting a photothermal conversion efficiency of up to 52.8%. Due to the mesoporous SiO2 coating, the CSP core-shell nanoparticles exhibited appropriate pore size, high pore volume, and large surface area; thus, they showed great potential to be used as drug carriers. Importantly, the release of uPA from CuS@mSiO2-PEG/uPA (CSPA) carriers can be promoted by the NIR laser irradiation. The drug loading content of uPA for the as-prepared NIR-triggered drug delivery system was calculated to be 8.2%, and the loading efficiency can be determined to be as high as 89.6%. Due to the excellent photothermal effect of CSP nanocarriers, the NIR-triggered drug delivery system can be used for infrared thermal imaging in vivo. The in vivo thrombolysis assessment demonstrated that the NIR-triggered drug delivery system showed excellent thrombolytic ability under the irradiation of an 808 nm laser, showing the combined therapy for thrombolysis. As far as we know, the CSPA core-shell nanoparticles used as NIR-triggered drug delivery systems for thrombolysis have not been reported.

Uncovered stent insertion for isolated superior mesenteric artery dissection.

ABSTRACT: The aim of this study is to describe our clinical outcomes in isolated superior mesenteric artery dissection (SMAD) patients that underwent uncovered stent insertion.Between January 2016 and August 2019, consecutive isolated SMAD patients at our center were treated via uncovered stent insertion. Both short- and long-term outcomes in these patients were analyzed.Over the course of the study period, 11 total isolated SMAD patients meeting the criteria for stent insertion at our hospital were treated via uncovered stent insertion. Stent placement across the SMAD site was successful in all patients, with 1 stent being used per patient. There were no instances of procedure-related complications, and the median operative duration was 60 minutes. Patency of the distal superior mesenteric artery and branches thereof was achieved in all cases. Patients experienced progressive SMAD-related symptom relief and were followed for 6 to 49 months (median: 22 months). Over this follow-up period, the obliteration of the dissection was observed within 3 months in all patients. We did not detect any instances of stent occlusion, bowel ischemia, or anti-platelet-related bleeding during the follow-up period.Uncovered stent insertion can achieve favorable short- and long-term outcomes in isolated SMAD patients.

Endovascular treatment with stenting of celiac artery aneurysms.

This study aimed to detail the clinical outcomes of patients suffering from celiac arterial aneurysm (CAA) that underwent treatment via stent occlusion.This is a single-center, retrospective study. A total of 8 consecutive CAA patients were treated via stent occlusion from March 2014 to September 2018 at our hospital. Follow-up computed tomography was conducted after stenting at 1, 3, 6, and 12-month time points and every year thereafter. Both short- and long-term outcomes were assessed.In total, 8 stents were inserted into these 8 patients, with 2 being uncovered and 6 being covered stents. In 2 patients, stents were positioned in the celiac artery, while in the remaining 6 patients they were placed in the celiac and common hepatic arteries. The median operative duration was 66 minutes. No patients exhibited procedure-associated complications, and the median follow-up duration was 39 months (range: 18-72). Abdominal contrast-enhanced CT analyses of these patients exhibited stent and distal artery patency in 100% of patients, together with CAA obliteration. Visceral necrosis did not occur in any patients over the follow-up period.Stent occlusion can be safely and effectively used to treat CAA patients.

S-adenosylmethionine induces apoptosis and cycle arrest of gallbladder carcinoma cells by suppression of JAK2/STAT3 pathways.

S-adenosylmethionine (SAM) is a naturally occurring physiologic molecule found ubiquitously in all mammalian cells and an essential compound in many metabolic pathways. It has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, the precise molecular mechanism involved in its anticancer effect is not yet clear. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of SAM on human gallbladder cancer cells (GBC-SD and SGC-996) in vitro and in vivo. Cells were dealt with SAM and subjected to cell viability, colony formation, Hoechst staining, apoptosis, cycle arrest, western blot, and xenograft tumorigenicity assay. Experimental results showed that SAM could significantly inhibit the growth and proliferation and induce the apoptosis as well as cell cycle arrest in G0/G1 phase of GBC-SD and SGC-996 cells in a dose-dependent manner in vitro. The expression levels of p-JAK2, p-STAT3, Mcl-1, and Bcl-XL were significantly downregulated. In addition, inhibition of the JAK2/STAT3 pathway significantly enhanced the anti-apoptotic effect of SAM, suggesting the key roles of JAK2/STAT3 in the process. More importantly, our in vivo studies demonstrated that administration of SAM could significantly decrease the tumor weight and volume and immunohistochemistry analysis proved the downregulation of p-JAK2 and p-STAT3 in tumor tissues following SAM treatment, consistent with our in vitro results. In summary, our findings indicated that SAM can inhibit cell proliferation and induce apoptosis as well as cycle arrest of GBC cells by suppression of JAK2/STAT3 pathways and the dramatic effects of SAM hinting that SAM might be a useful therapeutic option for patients suffering from gallbladder cancer.

Copper chalcogenide materials as photothermal agents for cancer treatment.

Copper-based chalcogenide nanomaterials have made tremendous progress for cancer theranostics due to their simple preparation, low cost, stable performance, and easy functionalization. But a systematic review and analysis about them does not exist. Therefore, we offer an account, mainly focusing on the design and functionalization of the copper-based chalcogenide nanomaterials for cancer theranostics, aiming to briefly demonstrate the design and concepts, summarize some of the past studies and analyze the development trends in the copper-based chalcogenide nanomaterials for clinical application.

Elevated MIR100HG promotes colorectal cancer metastasis and is associated with poor prognosis.

mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG), which is located on chromosome 11q24.1, is a polycistronic microRNA host gene. MIR100HG overexpression in colorectal cancer (CRC) has been demonstrated to be associated with cetuximab resistance; however, the role of MIR100HG in CRC metastasis remains unclear. The present study aimed to investigate the impact of aberrant MIR100HG expression on metastasis and prognosis in patients with CRC. The results from reverse transcription-quantitative PCR demonstrated that MIR100HG expression was higher in CRC tissues compared with in corresponding normal mucosa tissues. In particular, MIR100HG expression was higher in advanced CRC compared with in early stage CRC. Furthermore, the results from Kaplan-Meier analysis followed by a log-rank test revealed that patients with CRC and high MIR100HG expression exhibited poorer disease-free survival and overall survival compared with patients with CRC and lower MIR100HG expression. Furthermore, results from in vitro Transwell assays and in vivo animal assays demonstrated that upregulated MIR100HG expression promoted CRC cell migration and invasion and the formation of liver metastatic colonies in mice. In conclusion, the present study demonstrated that MIR100HG overexpression may contribute to the progression of CRC and may predict a poorer prognosis in patients with CRC. MIR100HG may therefore be considered as a novel therapeutic target and a prognostic biomarker in patients with CRC.

The Role of the miR-21/SPRY2 Axis in Modulating Proangiogenic Factors, Epithelial Phenotypes, and Wound Healing in Corneal Epithelial Cells.

Purpose: Subconjunctival injection of antagomir-21 attenuates the progression of corneal neovascularization. We examined the underlying mechanism by investigating the regulation of microRNA (miR)-21 expression and the involvement of miR-21 in the homeostasis of corneal epithelial cells. Methods: Corneal epithelial cells were cultured with TGF-ß1 and/or under hypoxia conditions. miR-21 expression was measured by quantitative PCR. The direct targets of miR-21 were validated by the 3'-UTR luciferase reporter assay. Alterations of proangiogenic signaling and the epithelial-mesenchymal transition (EMT) phenotype after miR-21/Sprouty2 (SPRY2) knockdown were examined by Western blotting. The effect of conditioned medium on angiogenesis was assessed using the tube formation assay. Wound healing was evaluated by the migration and scratch assays. Results: TGF-ß1 or hypoxia upregulated miR-21, and miR-21 silencing abolished TGF-ß1/hypoxia-induced hypoxia inducible factor (HIF)-1α and VEGF expression. miR-21 inhibited SPRY2 by directly targeting its 3'-UTR. Simultaneous silencing of miR-21 and SPRY2 significantly upregulated p-ERK, HIF-1α, and VEGF and promoted angiogenesis. Induction of miR-21 or inhibition of SPRY2 reduced the levels of cytokeratin (CK)-3 and CK-12 and promoted EMT. Transwell and wound healing assays indicated that miR-21 promoted cell migration. Conclusions: TGF-ß1 or hypoxia induced miR-21 and inhibited SPRY2, thereby enhancing proangiogenic signaling, suppressing the epithelial phenotype, and promoting wound healing in corneal epithelial cells.

Follicle-stimulating hormone inhibits cervical cancer via NF-κB pathway.

BACKGROUND: Follicle-stimulating hormone (FSH) has multiple biological functions. It is currently considered that FSH can inhibit cervical cancer, and our aim was to explore the underlying molecular mechanisms. MATERIALS AND METHODS: An in vivo experiment using nude mice injected with HeLa cells was performed. Flow cytometry, western blotting, and real-time quantitative PCR analyses were done. RESULTS: Twenty one days after injection of HeLa cells, the subcutaneous tumor mass was significantly lower (P<0.01) in mice treated with 20 mIU/mL FSH, but did not disappear. In vitro observations indicated that FSH might inhibit cell proliferation and activate cell apoptosis to induce the reduction of HeLa cells. The mRNA and protein levels of Cyclin D1, Cyclin E1, and Caspase 3 changed accordingly as expected in vivo and in vitro. Moreover, FSH inactivated the nuclear factor-kappa B (NF-κB) pathway in subcutaneous tumors; the NF-κB(p65) activity in HeLa cells was significantly decreased using 20 mIU/mL FSH and was increased when FSH was administered along with lipopolysaccharide, accompanied by the same change of cell number. Further, FSH accelerated protein kinase A (PKA) activity, but inactivated glycogen synthase kinase 3 beta (GSK-3ß) activity. Specific inhibition of PKA and/or GSK-3ß provided in vitro evidence that directly supported the FSH-mediated inhibition of GSK-3ß to inactivate NF-κB via the promotion of PKA activity. CONCLUSION: Our data are the first description of the molecular regulatory mechanisms of FSH-mediated inhibition of the development of cervical cancer by decreasing the cell cycle and activating cell apoptosis via the PKA/GSK-3ß/NF-κB pathway.

As an independent prognostic factor, USP6 promotes the invasion and metastasis of colon cancer.

The lack of efficient tumor invasion and metastatic biomarkers led to high mortality rates in colon cancer patients. Aberrant expression of ubiquitin-specific protease 6 (USP6) was involved in several diseases including cancer, while its role in the progression of colon cancer was still unclear. In this study, USP6 was evaluated at both mRNA and protein levels by using RT-PCR, western blot and immunohistochemistry staining analyses. The results revealed that high USP6 expression predicted poor disease-specific survival and overall survival through Kaplan-Meier analyses with log-rank tests, univariate and multivariate Cox analyses. Furthermore, cell function assay demonstrated that USP6 could promote colon cancer cells' invasion in vitro and liver metastasis in vivo. These findings indicated that high USP6 expression contributed to the progression of colon cancer and USP6 may be a valuable prognostic factor in patients with colon cancer.

MicroRNA-379 Suppresses Cervical Cancer Cell Proliferation and Invasion by Directly Targeting V-crk Avian Sarcoma Virus CT10 Oncogene Homolog-Like (CRKL).

Cervical cancer is the fourth most common malignancy among females worldwide. MicroRNA-379 (miR-379) is aberrantly expressed in multiple human cancer types. However, the expression pattern, roles, and detailed regulatory mechanisms of miR-379 in cervical cancer remain unknown. In this study, we found that miR-379 expression was downregulated in cervical cancer tissues and cell lines. Low miR-379 expression was correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and distant metastasis. Additionally, miR-379 overexpression suppressed the proliferation and invasion of cervical cancer cells. Furthermore, V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) was identified as a direct target of miR-379 in cervical cancer. CRKL was upregulated in cancer tissues and negatively correlated with miR-379 expression. Moreover, restored CRKL expression rescued the inhibitory effects of miR-379 overexpression on cell proliferation and invasion. In conclusion, miR-379 may serve as a tumor suppressor in cervical cancer by directly targeting CRKL. Restoring miR-379 expression may be an effective strategy for the treatment of cervical cancer.

In Situ Laser Fenestration Is a Feasible Method for Revascularization of Aortic Arch During Thoracic Endovascular Aortic Repair.

BACKGROUND: Reconstruction of the aortic major branches during thoracic endovascular aortic repair is complicated because of the complex anatomic configuration and variation of the aortic arch. In situ laser fenestration has shown great potential for the revascularization of aortic branches. This study aims to evaluate the feasibility, effectiveness, and safety of in situ laser fenestration on the three branches of the aortic arch during thoracic endovascular aortic repair. METHODS AND RESULTS: Before clinical application, the polytetrafluoroethylene and Dacron grafts were fenestrated by an 810-nm laser system ex vivo, which did not damage the bare metal portion of the endografts and created a clean fenestration while maintaining the integrity of the endografts. In vivo, 6 anesthetized female swine survived after this operation, including stent-graft implantation in the aortic arches, laser fenestration, and conduit implantation through the innominate arteries and the left carotid arteries. Based on the animal experiments, in situ laser fenestration during thoracic endovascular aortic repair was successively performed on 24 patients (aged 33-86 years) with aortic artery diseases (dissection type A: n=4, type B: n=7, aneurysm: n=2, mural thrombus: n=7). Fenestration of 3 aortic branches was performed in 2 (8.3%) patients. Both the left carotid artery and the left subclavian artery were fenestrated in 6 (25%) patients. Only left subclavian artery fenestration surgery was done in 16 (66.7%) patients. Among these patients, 1 fenestration was abandoned secondary to an acute takeoff of the innominate artery in a type III aortic arch. The average operative time was 137±15 minutes. The technical success rate was 95.8% (n=23). No fenestration-related complications or neurological morbidity occurred after this operation. During a mean postoperative 10-month follow-up (range: 2-17 months), 1 patient died of severe pneumonia, and all the left subclavian artery and carotid artery stents were patent with no fenestration-related endoleaks upon computed tomography angiography images. CONCLUSIONS: In situ laser fenestration is a feasible, effective, rapid, repeatable, and safe option for the reconstruction of aortic arch during thoracic endovascular aortic repair, which might be available to revascularize the 3 branches. However, follow-up periods should be extended to evaluate the robustness of this technique.

Elevated expression of KLK8 predicts poor prognosis in colorectal cancer.

KLK8, also known as neuropsin, is one of fifteen members of the human kallikrein-related peptidase (KLK) gene family, which consists of enzymes with serine protease enzymatic activity. Aberrant KLK8 expression has been reported in several malignancies. However, the clinicopathological significance and prognostic value of KLK8 expression in colorectal cancer (CRC) are unknown. Therefore, analysis of public datasets, quantitative real-time PCR and western blot analysis were performed to assess KLK8 expression in CRC at both the mRNA and protein level. KLK8 expression was also assessed by immunohistochemistry in a tissue microarray containing 124 CRC specimens. We observed that KLK8 was overexpressed in CRC tissues and was significantly associated with TNM stage, vascular invasion, differentiation and AJCC stage. Univariate and multivariate Cox analyses confirmed that KLK8 is a significant independent prognostic factor for both DFS and OS. Cell function assays also indicated that KLK8 could facilitate CRC cell proliferation, migration and invasion in vitro. In conclusion, elevated KLK8 expression was correlated with the progression of CRC and is a potential independent prognostic indicator for CRC.

Gold nanorods as a theranostic platform for in vitro and in vivo imaging and photothermal therapy of inflammatory macrophages.

Inflammatory macrophages play pivotal roles in the development of atherosclerosis. Theranostics, a promising approach for local imaging and photothermal therapy of inflammatory macrophages, has drawn increasing attention in biomedical research. In this study, gold nanorods (Au NRs) were synthesized, and their in vitro photothermal effects on the macrophage cell line (Ana-1 cells) under 808 nm near infrared reflection (NIR) were investigated by the CCK8 assay, calcein AM/PI staining, flow cytometry, transmission electron microscopy (TEM), silver staining and in vitro micro-computed tomography (CT) imaging. These Au NRs were then applied to an apolipoprotein E knockout (Apo E) mouse model to evaluate their effects on in vivo CT imaging and their effectiveness as for the subsequent photothermal therapy of macrophages in femoral artery restenosis under 808 nm laser irradiation. In vitro photothermal ablation treatment using Au NRs exhibited a significant cell-killing efficacy of macrophages, even at relatively low concentrations of Au NRs and low NIR powers. In addition, the in vivo results demonstrated that the Au NRs are effective for in vivo imaging and photothermal therapy of inflammatory macrophages in femoral artery restenosis. This study shows that Au nanorods are a promising theranostic platform for the diagnosis and photothermal therapy of inflammation-associated diseases.

Periostin enhances adipose-derived stem cell adhesion, migration, and therapeutic efficiency in Apo E deficient mice with hind limb ischemia.

INTRODUCTION: Therapeutic angiogenesis by transplantation of autologous/allogeneic adipose-derived stem cells (ADSCs) is a potential approach for severe ischemic diseases. However, poor viability, adhesion, migration and differentiation limit the therapeutic efficiency after the cells were transplanted into the targeted area. Periostin, an extracellular matrix protein, exhibits a critical role in wound repair as well as promotes cell adhesion, survival, and angiogenesis. METHOD: ADSCs were obtained and genetically engineered with periostin gene (P-ADSCs). The viability, proliferation, migration, and apoptosis of P-ADSCs under hypoxia were analyzed. Moreover, P-ADSCs were implanted into Apo E deficient mice with hind limb ischemia. The Laser Doppler perfusion index, immunofluorescence, and histological pathology assay were tested to evaluate the therapeutic effects. The associated molecular mechanism of periostin on the proliferation, adhesion, migration, and differentiation of ADSCs was also analyzed. RESULTS: The in vitro studies have shown that periostin-transfected ADSCs (P-ADSCs) promoted viability, proliferation, and migration of ADSCs. Apoptosis of ADSCs was inhibited under hypoxic conditions. The Laser Doppler perfusion index was significantly higher in the P-ADSCs group compared with that in the ADSC and control groups after 4 weeks. Immunofluorescence and histological pathology assay showed that the P-ADSCs were in and around the ischemic sites, and some cells differentiated into capillaries and endothelium. Microvessel densities were significantly improved in P-ADSCs group compared with those in the control group. The molecular mechanisms that provide the beneficial effects of periostin were connected with the upregulated expression of integrinß1/FAK/PI3K/Akt/eNOS signal pathway and the increased secretion of growth factors. CONCLUSION: Overexpression of periostin by gene transfection on ADSCs promotes survival, migration, and therapeutic efficiency, which will bring new insights into the treatment of critical limb ischemia.

An effective approach to reduce inflammation and stenosis in carotid artery: polypyrrole nanoparticle-based photothermal therapy.

Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE(-/-) mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.

Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles.

Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS). Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 µM) and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases.

Polyethylene glycol-modified dendrimer-entrapped gold nanoparticles enhance CT imaging of blood pool in atherosclerotic mice.

We report a new use of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for in vitro and in vivo imaging of atherosclerotic mice by computed tomography (CT). In this study, Au DENPs were synthesized using poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5.NH2) modified by PEG monomethyl ether (G5.NH2-mPEG20) as templates. In vitro cytotoxicity and flow cytometry assays show that the formed PEGylated Au DENPs have good biocompatibility and are non-cytotoxic at the Au concentration up to 300 µM. Silver staining and transmission electron microscopy (TEM) further confirm that the Au DENPs are able to be uptaken by macrophages and are located dominantly in the lysosomes of the cells. Importantly, the formed PEGylated Au DENPs are able to be used for CT imaging of murine macrophages in vitro and macrophages in atherosclerotic mice in vivo using apolipoprotein-E-gene-deficient mice as a model. These findings suggest that the formed PEGylated Au DENPs are a promising contrast agent for CT imaging of atherosclerosis.