Sonic hedgehog signaling promotes angiogenesis of endothelial progenitor cells to improve pressure ulcers healing by PI3K/AKT/eNOS signaling.

BACKGROUND: Pressure ulcer is a severe disease in the paralyzed and aging populations. Endothelial progenitor cells (EPCs) are able to regulate ulcer healing by modulating angiogenesis, but the molecular mechanism is still obscure. Sonic hedgehog (SHH) signaling contributes to angiogenesis in various diseases and has been identified to modulate EPCs function. Here, we aimed to explore the significance of SHH signaling in EPCs function during pressure ulcers. METHODS: The EPCs were isolated and characterized by the expression of DiI-acLDL and bind fluorescein iso-thiocyanate UEA-1. Cell proliferation was detected by cell counting kit 8 (CCK-8). The DiI-acLDL and bind fluorescein iso-thiocyanate UEA-1 were analyzed by immunofluorescent analysis. The angiogenesis of EPCs was analyzed by tube formation assay. The pressure ulcers rat model was constructed, the wound injury was analyzed by H&E staining and angiogenesis was analyzed by the accumulation of CD31 based on immunofluorescent analysis. RESULTS: The expression of patched-1 and Gli-1 was enhanced by SHH activator SAG but reduced by SHH inhibitor cyclopamine in the EPCsThe PI3K, Akt, eNOS expression and the Akt phosphorylation were induced by SAG, while the treatment of cyclopamine presented a reversed result. The proliferation and migration of EPCs were enhanced by SAG but repressed by cyclopamine or PI3K/AKT/eNOS signaling inhibitor Y294002, in which the co-treatment of Y294002 could reverse the effect of SAG. CONCLUSIONS: Thus, we found that SHH signaling activated angiogenesis properties of EPCs to improve pressure ulcers healing by PI3K/AKT/eNOS signaling. SHH signaling may serve as the potential target for attenuating pressure ulcers.

Calcium silicate-stimulated adipose-derived stem cells promote angiogenesis and improve skin wound healing.

Skin wound healing is a complicated process involving proliferation, inflammation, coagulation, and hemostasis, and scar tissue formation of wound repairing. Adipose-derived stem cells (ADSCs) have presented potential therapeutic effects in the non-healing and chronic wound. Calcium silicate (CS) ceramics have been identified as a new type of bioceramics for tissue construction and regeneration. Here, we aimed to explore the impact of CS on the regulation of ADSCs-mediated wound healing. Significantly, CS was able to dose-dependently enhance the proliferation of ADSCs. CS inhibited terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in the H2O2-treated ADSCs. Similarly, the Bcl-2 expression was elevated while Bax and cleaved caspase-3 expression were repressed by CS in the cells. CS could induce migration and reduce oxidative stress of ADSCs. Moreover, immunofluorescence analysis and Western blot analysis showed that CS could promote CXCR4 expression in ADSCs. Moreover, CS-stimulated ADSCs enhanced migration and angiogenic capacity of HUVEC. Importantly, CS-stimulated ADSCs improved wound healing in full-thickness skin defect mouse model. Thus, we conclude that CS improves ADSCs-attenuated wound healing in vivo and in vitro. Our finding presents novel insight in the scenario that CS regulates ADSCs and wound healing. CS may be applied as potential materials for the treatment of wound healing.

A label-free fluorescent biosensor based on specific aptamer-templated silver nanoclusters for the detection of tetracycline.

Tetracycline (TET) is a broad-spectrum antibiotic commonly used in the treatment of animals. TET residues in food inevitably threaten human health. High-performance analytical techniques for TET detection are required in food quality assessment. The objective of this study was to establish a label-free fluorescent biosensor for TET detection using specific aptamer-templated silver nanoclusters (AgNCs). An aptamer with a high specific binding ability to TET was used to synthesize a novel DNA-templated AgNCs (DNA-AgNCs). When TET is present, the aptamer's conformation switched from an antiparallel G-quadruplex to a hairpin structure, altering the connection between AgNCs and the aptamer. Following the transformation of AgNCs into large sized silver nanoparticles (AgNPs), a fluorescence decrease was detected. When used to detect TET in milk, the proposed biosensor displayed high sensitivity and selectivity, with a limit of detection of 11.46 ng/mL, a linear range of 20 ng/mL-10 g/mL, and good recoveries of 97.7-114.6% under optimized conditions. These results demonstrate that the proposed biosensor was successfully used to determine TET quantitatively in food samples, suggesting that our method provides an efficient and novel reference for detecting antibiotics in food while expanding the application of DNA-AgNCs in related fields.

Microwave ablation vs. surgery for papillary thyroid carcinoma with minimal sonographic extrathyroid extension: a multicentre prospective study.

OBJECTIVES: Minimal extrathyroid extension (mETE) was removed from the TNM staging system. This study was designed prospectively to compare the safety and efficacy of microwave ablation (MWA) versus surgery for treating T1N0M0 papillary thyroid carcinomas (PTC) with sonographically detected mETE. METHODS: From December 2019 to April 2021, 198 patients with T1N0M0 mETE-PTCs evaluated by preoperative ultrasound from 10 hospitals were included. Ninety-two patients elected MWA, and 106 patients elected surgery for treatment. MWA was performed using extensive ablation with hydrodissection. Surgery consisted of lobectomy with ipsilateral central lymph node dissection (CLD), lobe and isthmus excision with ipsilateral CLD and total thyroidectomy with ipsilateral CLD. The rates of technical success, cost, oncologic outcomes, complications and quality of life of the two groups were assessed. RESULTS: The follow-up times for the MWA and surgery groups were 12.7 ± 4.1 and 12.6 ± 5.0 months, respectively. The technical success rate was 100% for both groups. Oncological outcomes of the two groups were similar during the follow-up (all p > 0.05). The MWA group had a shorter operation time, less blood loss and lower costs (all p < 0.001). Three complications (3.3%) were reported in the MWA group and 4 (3.8%) in the surgery group (p = 0.846). The surgery group had higher scores for scar problems and anxiety (p < 0.001 and p = 0.003, respectively). CONCLUSIONS: Microwave ablation was comparable in the short term to surgery in terms of treatment safety and efficacy in selected patients with T1N0M0 mETE-PTC detected by ultrasound. KEY POINTS: • Microwave ablation is comparable to surgery in the safety and short-term efficacy for PTCs with sonographically detected mETE. • Thermal ablation is technically feasible for mETE-PTC treatment. • Patients with mETE-PTC have similar quality of life in the two groups, except for worse scar problems and anxiety in the surgery group.

A highly sensitive competitive aptasensor for AFB1 detection based on an exonuclease-assisted target recycling amplification strategy.

Aflatoxin B1 (AFB1) is a typical mycotoxin found in agricultural products, and poses a huge threat to both humans and animals. Accurate and rapid measurement of AFB1 is essential for environmental analysis and food safety. Based on molecular docking simulation design and exonuclease-assisted target recycling amplification, we designed a competitive fluorescence aptasensor to detect AFB1 rapidly and sensitively. According to the molecular docking simulations, a complementary strand (cDNA) was designed by searching for potential binding sites of the aptamer, which had the lowest binding energy. Magnetic beads modified with biotin-Apt were used as the capture probe, while FAM-labeled cDNA acted as the reporter probe. By using EXO I for target recycling amplification, this aptasensor was highly sensitive and selective for AFB1. The detection limit of the suggested aptasensor under optimal conditions was 0.36 ng mL-1 (S/N = 3) in the range of 1-1000 ng mL-1 (R2 = 0.991). The developed aptasensor was successfully used to analyze AFB1 in oil samples.

SIX1 attenuates inflammation and rheumatoid arthritis by silencing MyD88-dependent TLR1/2 signaling.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease that severely affects the patients' quality of life. Sine oculis homeobox 1 (SIX1) has been reported as a key regulator of organogenesis and inflammation. This study aimed to explore the effects of SIX1 on RA. METHODS: Wistar rats were immunized with type II collagen to induce an animal model of RA. RA synovial fibroblasts (RASFs) were isolated from the rats. SIX1 expression in RA rats and RASFs was detected by qRT-PCR and western blot. CCK-8, EdU, transwell, flow cytometer, and ELISA were conducted to assay the effects of SIX1 on RASFs. The effects of SIX1 on RA rats were studied by Safranin O staining, H&E staining, and ELISA. Besides, GSEA and KEGG analysis were used to predict the underlying signaling pathways. RESULTS: SIX1 was low expressed in synovial tissue of RA rats and RASFs. SIX1 overexpression inhibited the proliferation, invasion, and levels of TNF-α, IL-6, and IL-8 in RASFs. However, SIX1 overexpression promoted the apoptosis of RASFs. SIX1 overexpression enhanced body weight, and attenuated the cartilage damage, pathological injury, and pro-inflammatory cytokine release of RA rat model. MyD88-dependent TLR1/2 might be a downstream signaling of SIX1. RelA acted as a transcription factor of TLR1/2, and SIX1 inhibited TLR1/2 signaling possibly via interaction with RelA. Adding with Pam3CSK4, a specific agonist of TLR1/2 signaling, attenuated the effects of SIX1 on RASFs. CONCLUSION: SIX1 attenuated inflammation and RA by silencing MyD88-dependent TLR1/2 signaling. SIX1 may be a promising target for RA treatment.

The occurrence, potential toxicity, and toxicity mechanism of bisphenol S, a substitute of bisphenol A: A critical review of recent progress.

Bisphenol S (BPS) has been introduced into the industry as a safer alternative to bisphenol A (BPA). The distribution of BPS has recently become an important issue worldwide, but investigations on the toxicity and mechanisms of BPS remain limited. A review of the literature reveals that BPS has widespread presence in environmental media, such as indoor dust, surface water, sediments, and sewage sludge. It has been detected in plants, paper products, some food items, and even in the human body. In addition, compared to BPA, BPS has a lower acute toxicity, similar or less endocrine disruption, similar neurotoxicity and immunotoxicity, and lower reproductive and developmental toxicity. The mechanisms underlying BPS toxicity may be related to the chemical properties of BPS in the human body, including interactions with estrogen receptors, and binding to DNA and some proteins, subsequently including exerting oxidative stress. However, further investigation on the potential risks of BPS to humans and its mechanisms of toxicity should be conducted to better understand and control the risks of such novel chemicals.

A Density-Changing Centrifugation Method for Efficient Separation of Free Drugs from Drug-Loaded Particulate Delivery Systems.

Commonly used separation techniques, such as ultracentrifugation, chromatography, and membrane separation, have inherent drawbacks that limit their usage. Herein, we introduced a new separation method, density-changing centrifugation (DCC), which is based on trisodium citrate (TC) and ultracentrifugation. Paclitaxel-loaded cationic solid lipid nanoparticles (SLNs/PTX) and doxorubicin-loaded PEGylated liposomes (Lipo/Dox) were prepared as model drug delivery particulates. After optimizing TC concentration and centrifugal conditions, DCC showed superior separation efficiency and accuracy over common ultracentrifugation and ultrafiltration methods and displayed comparable or even better separation efficiency compared with size-exclusion chromatography, as demonstrated by the determination of encapsulation efficiency, Tyndall effect, transmittance, and drug recovery. DCC was also proven to minimally impact the size distribution, surface morphology, and thermal properties of the nanoparticles and liposomes, and moreover, it did not affect the determination of drug concentrations. Together, DCC has been demonstrated as a neat and effective method for the separation of free drugs from drug-loaded SLNs and liposomes, which shall be of great benefit for the development of particulate based delivery systems.

Clinical applicability of monitoring pulmonary artery blood flow acceleration time variations in monitoring fetal pulmonary artery pressure.

BACKGROUND: In recent years, pulmonary artery blood flow acceleration time (AT) has been believed to be applicable in the examination of fetal lung development. OBJECTIVES: This study aims to evaluate the clinical significance of pulmonary artery blood flow AT as a parameter in monitoring of fetal pulmonary artery pressure. MATERIAL AND METHODS: A total of 31 fetuses in midor late-term pregnancy with tricuspid regurgitation were set as the study group (congenital heart disease with a tricuspid regurgitation pressure difference of more than 20 mm Hg was excluded). A total of 68 normal fetuses in midor late-term pregnancy were selected as the control group (strictly screened for tricuspid regurgitation, congenital heart disease and other congenital diseases before inclusion). The average ATs of both groups were calculated. Correlations of pulmonary artery systolic pressure (PASP) and AT, as well as the ratio of AT to right ventricular ejection time (ET) (AT/ET ratio) of both groups were investigated by 1-way analysis of variance (ANOVA). RESULTS: The average AT of the study group was significantly lower than that of the control group (p < 0.0001). In the study group, AT negatively correlated with PASP (r = -0.52; p < 0.01), AT/ET ratio negatively correlated with PASP (r = -0.52; p < 0.01) and both showed statistical significance. CONCLUSIONS: The results indicated that fetuses in the study group showed lower ATs and AT/ET ratios than the control group. Acceleration times and AT/ET ratios decreased as PASP increased. Thus, AT and AT/ET ratio can be used clinically as new parameters for the qualitative and - to some extent - quantitative evaluation of fetal pulmonary artery pressure.

The in vivo action of chronic bisphenol F showing potential immune disturbance in juvenile common carp (Cyprinus carpio).

Bisphenol F (BPF) has been increasingly introduced into industrial applications as a replacement for bisphenol A (BPA), and has emerged as a ubiquitous environmental contaminant worldwide. Few studies have assessed the in vivo toxicities of BPF, particularly long-term exposure toxicities. In the present study, we examined whether long-term BPF exposure in vivo would evoke oxidative stress in the immune system of juvenile common carp. The results suggested that BPF exposure increased ROS content, oxidative stress indices, complement component 3, and immunoglobulin M contents, as well as the expression of inflammatory cytokine genes. Moreover, higher levels of nf-κb p65 gene expression were correlated with the induced ROS content and NF-κB pathway-associated genes, a strong indication that the mode of action of BPF is related to the NF-κB signaling pathway. We also provide evidence that the effects of BPF are comparable to those of BPA with regards to regulation of the immune response in teleosts, and therefore suggest that such chemical analogs should be thoroughly evaluated for their potential toxicity before they can be considered as "safer" replacements.

Outcome Assessments of Patients with Posttraumatic "Ultra-Time Vascular Injuries" of the Extremities.

The management of posttraumatic vascular injury that presents after 8 h, or "ultra-time vascular injury", is daunting, and inciting recognition of this injury is vital. We retrospectively analyzed 29 patients with ultra-time vascular injuries to determine the patients' demographic characteristics and identify the determinants for amputation and disability. The age distribution of the high-risk population was from 18 years to 40 years, which indicated that these patients had plenty of productive life remaining. Injuries to the lower limbs (79.31%) were over four times more common than injuries to the upper limbs (17.24%), and open and blunt injuries occurred most commonly. The overall rate of limb salvage was 82.76% (24/29) and limb function is excellent in 45.83% (11/24) of the patients. The remaining patients experienced different degrees of disability in their limbs, which was determined by the anatomic location of the injury, and the presence of a combined arterial and venous injury, nerve injury, and complex soft tissue injury, as well as the occurrence of compartment syndrome. Hence, we recommend limb-salvage treatment for patients with traumatic ultra-time vascular injuries, particularly for those aged between 18 years and 40 years. Furthermore, we encourage the development of limb-salvage techniques for ultra-time vascular injuries.