Rigid-flexible nanocarriers loaded with active peptides for antioxidant and anti-inflammatory applications in skin.

Peptides are recognized as highly effective and safe bioactive ingredients. However, t their practical application is limited and hampered by harsh conditions for practical drug delivery. Hence, a novel peptide nanocarrier of copper peptide (GHK-Cu) encapsulation developed by liposome technology combined with the classical Chinese concept of rigidity and flexibility. Different polyols were selected as modification ligands for phospholipid bilayers to construct a nano drug-carrying system with high loading rate, good stability and biocompatibility. In vitro, this complex not only significantly retarded the release ability of copper peptides, but also enabled copper peptides to be effectively resistant to enzymatic degradation. Furthermore, cellular experiments showed that this system mainly regulates Nrf2, SIRT1, and PEG2/COX-2-related signaling pathways, thus effectively counteracting cellular inflammation, senescence, and apoptosis from oxidative damage. Interestingly, a green, non-toxic, efficient and convenient antioxidant system was developed for the prevention and deceleration of skin aging.

Enhanced therapeutic effect of PEDF-loaded mesenchymal stem cell-derived small extracellular vesicles against oxygen-induced retinopathy through increased stability and penetrability of PEDF.

BACKGROUND: Several common retinal diseases that cause blindness are characterised by pathological neovascularisation accompanied by inflammation and neurodegeneration, including retinopathy of prematurity (ROP), diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). The current treatment strategies for these diseases have limited benefits. Thus, safer and more effective alternative approaches are required. In this study, we loaded small extracellular vesicles (sEVs) derived from mesenchymal stem cell (MSC) with pigment epithelium-derived factor (PEDF), and tested the therapeutic effect of PEDF-loaded sEVs (PEDF-sEVs) using an oxygen induced retinopathy (OIR) mouse model, aiming to establish a new therapy strategy for the treatment of retinal pathological angiogenesis. RESULTS: We formulated PEDF-loaded sEVs (PEDF-sEVs) containing high concentrations of PEDF and evaluated their effects through in vivo and in vitro experiments. In OIR mice, PEDF-sEVs showed significantly better effects on retinal avascular areas, inflammation, and neuronal degeneration compared with the anti-vascular endothelial growth factor (VEGF) drug, which may indicate a possible advantage of PEDF-sEVs over anti-VEGF drugs in the treatment of pathological neovascularisation. In vitro, PEDF-sEVs greatly inhibited endothelial cell (EC) proliferation, migration, and tube formation by suppressing the VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT (also known as Protein Kinase B). All experiments and analyses were performed in triplicate. PEDF-sEVs were more effective than PEDF or sEVs alone, both in vitro and in vivo. Furthermore, to determine the distribution of PEDF-sEVs, we used DiD-labelled sEVs and FITC-labelled PEDF to track the sEVs and PEDF, respectively. We found that PEDF-sEVs effectively reduced the degradation of PEDF. CONCLUSIONS: Loading PEDF on sEVs effectively enhanced the anti-angiogenic, anti-inflammatory, and neuroprotective effects of PEDF by increasing the stability and penetrability. These results suggest a potential role for PEDF-sEVs in retinal pathological neovascularisation.

Receptors that bind to PEDF and their therapeutic roles in retinal diseases.

Retinal neovascular, neurodegenerative, and inflammatory diseases represented by diabetic retinopathy are the main types of blinding eye disorders that continually cause the increased burden worldwide. Pigment epithelium-derived factor (PEDF) is an endogenous factor with multiple effects including neurotrophic activity, anti-angiogenesis, anti-tumorigenesis, and anti-inflammatory activity. PEDF activity depends on the interaction with the proteins on the cell surface. At present, seven independent receptors, including adipose triglyceride lipase, laminin receptor, lipoprotein receptor-related protein, plexin domain-containing 1, plexin domain-containing 2, F1-ATP synthase, and vascular endothelial growth factor receptor 2, have been demonstrated and confirmed to be high affinity receptors for PEDF. Understanding the interactions between PEDF and PEDF receptors, their roles in normal cellular metabolism and the response the initiate in disease will be accommodating for elucidating the ways in which inflammation, angiogenesis, and neurodegeneration exacerbate disease pathology. In this review, we firstly introduce PEDF receptors comprehensively, focusing particularly on their expression pattern, ligands, related diseases, and signal transduction pathways, respectively. We also discuss the interactive ways of PEDF and receptors to expand the prospective understanding of PEDF receptors in the diagnosis and treatment of retinal diseases.

Selective Metallization on Ordinary Polymer Substrates by Laser Direct Activation of Copper Phosphate or Nickel Phosphate.

In recent years, selective metallization on polymer surfaces has attracted considerable attention due to its excellent properties and wide applications. This paper reports that copper phosphate (Cu3(PO4)2) or nickel phosphate (Ni3(PO4)2) was selected as laser-active material to successfully fabricate metallic patterns on ordinary polymer substrates by laser direct activation and electroless plating. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were utilized to characterize the interaction mechanism between a nanosecond-pulsed laser (355 and 1064 nm wavelengths) and Cu3(PO4)2 or Ni3(PO4)2. It was found that after 355 or 1064 nm laser activation with appropriate parameters, Cu+ was generated from Cu3(PO4)2, and NiO was generated from Ni3(PO4)2. At the same time, Cu+ or NiO adsorbed on the porous sponge-like microstructure of modified polycarbonate (PC), respectively, and acted as catalytic active centers to realize selective copper deposition in the laser-activated zone. Furthermore, the obtained copper layers were confirmed to possess good selectivity, electrical conductivity, and high adhesion strength (the highest grade of 5B). Moreover, from comparisons of Cu3(PO4)2 with Ni3(PO4)2 and of 355 nm laser activation with 1064 nm laser activation, the 1064 nm laser activation of Cu3(PO4)2 produced the most catalytic seeds (Cu+) and had the best catalytic effect.

Unilateral Biportal Endoscopy for the Treatment of Lumbar Disc Herniation.

Unilateral biportal endoscopy (UBE) is a minimally invasive spinal surgery technique increasingly employed in treating degenerative lumbar diseases, such as lumbar disc herniation, lumbar spinal stenosis, and spondylolisthesis. In UBE, two independent yet interconnected surgical channels are established-one for the endoscope and the other for surgical instruments-providing a broad and clear surgical field of view. UBE offers several advantages over traditional open surgery, including reduced tissue damage, shorter hospital stays, and faster recovery times. Additionally, it combines the benefits of microscopic surgery and interlaminar endoscopy, enhancing flexibility, accuracy, and reliability during the procedure. The learning curve for UBE is shorter than that for transforaminal endoscopy, as the surgical processes closely resemble those of conventional open surgery. Despite its favorable clinical outcomes, such as reduced blood loss and shorter hospitalization, UBE carries potential complications, including epidural hematoma, dural injury, and compression of the outlet nerve root. To mitigate these risks, it is crucial to ensure appropriate patient selection, apply the correct surgical technique, and engage in careful postoperative monitoring. This article provides a detailed summary of the step-by-step surgical techniques used in UBE for treating lumbar disc herniation. It serves as a comprehensive guide to enhance practitioners' understanding of UBE. The presentation also underscores the importance of rigorous training and expertise to ensure optimal patient outcomes.

Glycoproteomic analysis reveals the effects of bisecting GlcNAc in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second major subtype of primary liver cancer and has caused more and more attention with increasing incidence and mortality worldwide. Our previous study found that bisecting N-glycans are commonly increased in ICC, while the effects and potential functions of bisecting GlcNAc in ICC are still largely unclear. In this study, we further confirmed that the structures of bisecting GlcNAc were significantly up-regulated in ICC compared with paracancer tissues by glycoproteomic data and lectin histochemistry. The expression of its glycosyltransferase MGAT3 was also up-regulated in ICC tissues at both mRNA and protein levels, and expression of MGAT3 is negatively correlated with overall survival explored by bioinformatic analyses and published datasets from 255 patients. Next, the silencing of MGAT3 could inhibit the growth and invasion of ICC cells, and overexpressing of MGAT3 only promoted ICC cell invasion. Further glycoproteomic analysis showed that the commonly glycoproteins modified by bisecting GlcNAc after MGAT3-overexpression in two ICC cell lines were mainly involved in cell movement-related biological processes, such as cell adhesion, integrin-related and ECM-receptor interaction. This study sheds light on the potential effects of bisecting GlcNAc in ICC cells and suggests that MGAT3 might be used as a potential target in the therapy of ICC.

Arbuscular Mycorrhizal Fungi Reduce Cadmium Leaching from Sand Columns by Reducing Availability and Enhancing Uptake by Maize Roots.

To explore the effect of arbuscular mycorrhizal fungi (AMF) on the environmental migration of cadmium (Cd), a sand column-maize system containing 20 mg·L-1 Cd solution was used to investigate the AMF effect on maize growth, Cd uptake by maize, Cd adsorption by sand and Cd leaching loss. The results showed that AMF significantly increased the content of EE-GRSP and T-GRSP by 34.9% and 37.2%, respectively; the secretion of malonic acid, oxalic acid and succinic acid increased by 154.2%, 54.0% and 11.0%, respectively; the secretion of acetic acid and citric acid increased by 95.5% and 59.9%, respectively; and the length, surface area, volume, tip number and cross number of maize roots decreased by 10%, 15%, 17%, 20% and 36.4%, respectively. AMF significantly increased Cd adsorption by sand by 6.2%, Cd uptake by maize by 68.1%, and Cd leaching loss by 84.6%. In the sand column-maize system, 92.3% of the total Cd was adsorbed by sand, 5.9% was taken up by maize and 1.8% was lost due to leaching. Moreover, Cd adsorption by sand was significantly positively correlated with the GRSP content and oxalic acid secretion, and Cd uptake by roots was significantly negatively correlated with Cd leaching loss. Overall, AMF reduced the loss of Cd in the leaching solution by promoting the release of oxalic acid and GRSP, increasing the adsorption of Cd in the sand and fixing the Cd in the plant to the roots.

Cervical single open-door laminoplasty with or without local lateral mass screw fixation and fusion to treat cervical spinal cord injuries accompanied by segmental spinal canal stenosis.

Study Design: Retrospective. Objectives: To investigate the efficacy of cervical single open-door laminoplasty with and without local lateral mass screw fixation and fusion as treatments for cervical spinal cord injuries accompanied by multisegmental spinal canal stenosis. Setting: The Second Affiliated Hospital, School of Medicine, Zhejiang University. Methods: Of all enrolled patients, 42 formed a stable group who underwent cervical single open-door laminoplasty alone and 14 formed an unstable group who underwent the procedure combined with lateral mass screw fixation and fusion. Neurological function was evaluated before surgery, at discharge, and at final follow-up using the American Spinal Cord Injury Association (ASIA) impairment scale and the Japanese Orthopedic Association (JOA) score. Results: ASIA scores reflected improved neurological function in 52.5% of the stable group (15 with grade-D and 4 with grade-A injuries did not improve) and 45.5% of the unstable group (3 with grade-D and 3 with grade-A injuries did not improve). Postoperative JOA scores reflected 19.1% ± 21.6% improvement in the stable group and 18.6% ± 18.4% improvement in the unstable group (P > 0.05). Final follow-up JOA scores reflected 49.2% ± 31.7% improvement in the stable group and 47.1% ± 39.2% improvement in the unstable group (P > 0.05). Conclusions: Laminoplasty combined with local fusion aided the treatment of unstable cervical spinal cord injuries and spinal stenosis. Such stenosis is the main pathological factor causing multiple spinal cord compressions in patients with cervical spinal cord injuries.

Effect of an arbuscular mycorrhizal fungus on maize growth and cadmium migration in a sand column.

The ecological role of arbuscular mycorrhizal fungi (AMF) on altering cadmium (Cd) migration in polluted soil is still unresolved. The present experiment aimed to clarify whether AMF can reduce Cd loss due to leaching at different Cd concentrations (0, 5, 10, and 15 mg L-1) with maize as a host plant cultured in a sand column. The effects of the arbuscular mycorrhizal fungus Funneliformis mosseae on the root morphology, exudate content, and Cd uptake by maize and Cd loss due to leaching were investigated. The AMF altered the root morphology and exudate content of the maize, resulting in increases in the root length, volume, surface area, tips and branch number and in the contents of soluble sugars, proteins, and amino acids in the root exudates, and the AMF increased maize biomass and Cd uptake by 22.0-31.0%. Moreover, the AMF significantly increased the contents of total and easily extractable glomalin-related soil protein (GRSP), increased Cd adsorption by sand particles and decreased the Cd concentration in the solution at a depth of 20 cm, resulting in a 67.5-97.2% decrease in the Cd loss due to leaching from the sand column. Furthermore, the root exudate content was very significantly positively correlated with Cd adsorption by the sand particles. Root length was significantly positively correlated with Cd uptake by the maize roots, but the average root diameter was very significantly negatively correlated with Cd uptake by maize. Thus, the AMF altered Cd migration by increasing the contents of GRSP and exudates and root morphology, which contributed to reducing the Cd concentration in the solution and Cd loss due to leaching from the sand column. Taken together, these results indicated that AMF serve an ecological function in reducing Cd loss due to leaching from polluted soil.

MARCH8 Suppresses Tumor Metastasis and Mediates Degradation of STAT3 and CD44 in Breast Cancer Cells.

Protein stability is largely regulated by post-translational modifications, such as ubiquitination, which is mediated by ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin ligase E3 with substrate specificity. Membrane-associated RING-CH (MARCH) proteins represent one novel family of transmembrane E3 ligases which target glycoproteins for lysosomal destruction. While most of the MARCH family members are known to degrade membrane proteins in immune cells, their tumor-intrinsic role is largely unknown. In this study, we found that the expression of one MARCH family member, MARCH8, is specifically downregulated in breast cancer tissues and positively correlated with breast cancer survival rate according to bioinformatic analysis of The Cancer Genomic Atlas (TCGA) dataset. MARCH8 protein expression was also lower in a variety of human breast cancer cell lines in comparison to immortalized human mammary epithelial MCF-12A cells. Restoration of MARCH8 expression induced apoptosis in human breast cancer cell lines MDA-MB-231 and BT549. Stable expression of MARCH8 inhibited tumorigenesis and lung metastases of MDA-MB-231 cells in mice. Moreover, we discovered that the breast cancer stem-cell marker and metastasis driver CD44, a membrane protein, interacts with MARCH8 and is one of the glycoprotein targets subject to MARCH8-dependent lysosomal degradation. Unexpectedly, we identified a nonmembrane protein, signal transducer and transcription activator 3 (STAT3), as another essential ubiquitination target of MARCH8, whose degradation through the proteasome pathway is responsible for the proapoptotic changes mediated by MARCH8. These findings highlight a novel tumor-suppressing function of MARCH8 in targeting both membrane and nonmembrane protein targets required for the survival and metastasis of breast cancer cells.

Complete Genome Sequence of Burkholderia gladioli Phage Maja.

Burkholderia gladioli is a Gram-negative bacterium associated with cystic fibrosis infections. Here, we describe the genome sequence of B. gladioli phage Maja. Maja is most related to another Burkholderia phage, BcepF1, and may be a temperate phage, despite the absence of repressor or integrase homologs in its genome sequence.

Risk stratification for prediction of locoregional recurrence in patients with pathologic T1-2N0 breast cancer after mastectomy.

BACKGROUND: Previous studies have revealed that nearly 15-20% of selected high-risk T1-2N0 breast cancers developed LRR after mastectomy. This study is aim to indentify the risk factors of locoregional recurrence (LRR) in patients with pathologic T1-2N0 breast cancer after mastectomy in a real-world and distinguish individuals who warrant postmastectomy radiotherapy (PMRT). METHODS: Female patients treated from 1999 to 2014 in National Cancer Center of China were retrospectively reviewed. A competing risk model was developed to estimate the cumulative incidence of LRR with death treated as a competing event. RESULTS: A total of 4841 patients were eligible. All underwent mastectomy plus axillary nodes dissection or sentinel node biopsy without PMRT. With a median follow-up of 56.4 months (range, 1-222 months), the 5-year LRR rate was 3.9%.Besides treatment era, age ≤ 40 years old (p < 0.001, hazard ratio [HR] = 2.262), tumor located in inner quadrant (p < 0.001, HR = 2.236), T2 stage (p = 0.020, HR = 1.419), and negative expressions of estrogen receptor (ER) and progesterone receptor (PR) (p = 0.032, HR = 1.485), were patients-related independent risk factors for LRR. The 5-year LRR rates were 1.7, 3.5, and 15.0% for patients with zero, 1-2, and 3-4 risk factors (p < 0.001). CONCLUSIONS: Risk Stratification based on age, T stage, ER/PR status and tumor location can stratify patients with pT1-2 N0 breast cancer into subgroups with different risk of LRR. PMRT might be suggested for patients with 3-4 risk factors.

Timing of Chemotherapy and Radiotherapy Following Breast-Conserving Surgery for Early-Stage Breast Cancer: A Retrospective Analysis.

PURPOSE: To investigate the effect of chemotherapy and radiotherapy timing after breast conserving surgery (BCS) on recurrence and survival of women with early-stage breast cancer. PATIENTS AND METHODS: We retrospectively analyzed 900 patients who underwent BCS followed by both adjuvant chemotherapy and radiotherapy. Of these, 488 women received chemotherapy first (CT-first group) while the other 412 received radiotherapy first (RT-first group). Locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and further confirmed with propensity-score matching (PSM) and the Cox proportional hazards model. The optimal cut-off value of interval time from surgery to the start of chemotherapy was calculated by Maxstat. RESULTS: The median follow-up was 7.1 years. In pre-match analysis, the CT-first group had a significantly higher 8-year DFS than the RT-first group (90.4% vs. 83.1%, P = 0.005). PSM analysis of 528 patients indicated that the 8-year DFS (91.0% vs. 83.3%, P = 0.005) and DM (8.6% vs. 14.6%, P = 0.017) were significantly better in the CT-first group, but that the OS (P = 0.096) and LRR (P = 0.434) were similar. We found the optimal cut-off value of interval from surgery to chemotherapy was 12 weeks. Patients starting chemotherapy later than 12 weeks after surgery had significantly inferior survival outcomes. CONCLUSION: For women with breast cancer who require both chemotherapy and radiotherapy after BCS, adjuvant chemotherapy should be started within 12 weeks. Delaying the initiation of radiotherapy, for administration of long-course chemotherapy, does not compromise outcomes.

Long-term outcomes of moderately hypofractionated radiotherapy (67.5 Gy in 25 fractions) for prostate cancer confined to the pelvis: a single center retrospective analysis.

BACKGROUND: There is an increasing application of moderately hypofractionated radiotherapy for prostate cancer. We presented our outcomes and treatment-related toxicities with moderately hypofractionated (67.5 Gy in 25 fractions) radiotherapy for a group of advanced prostate cancer patients from China. METHODS: From November 2006 to December 2018, 246 consecutive patients with prostate cancer confined to the pelvis were treated with moderately hypofractionated radiotherapy (67.5 Gy in 25 fractions). 97.6% of the patients received a different duration of androgen deprivation therapy. Failure-free survival (FFS), prostate cancer-specific survival (PCSS), overall survival (OS), and cumulative grade ≥ 2 late toxicity were evaluated using the Kaplan-Meier actuarial method. Prognostic factors for FFS, PCSS, and OS were analyzed. RESULTS: The median follow-up time was 74 months (range: 6-150 months). For all patients, the 5- and 10-year FFS rates were 80.0% (95% CI: 74.7-85.7%) and 63.5% (95% CI 55.4-72.8%). The failure rates for the intermediate, high-risk, locally advanced, and N1 groups were 6.1%, 13.0%, 18.4%, and 35.7%, respectively (P = 0.003). Overall, 5- and 10-year PCSS rates were 95.7% (95% CI 93.0-98.5%) and 88.2% (95% CI 82.8-93.8%). Prostate cancer-specific mortality rates for the high-risk, locally advanced, and N1 groups were 4.0%, 8.2%, and 23.8%, respectively (P < 0.001). Overall, 5- and 10-year actuarial OS rates were 92.4% (95% CI 88.8-96.1%) and 72.7% (95% CI 64.8-81.5%). High level prostate-specific antigen and positive N stage were significantly associated with worse FFS (P < 0.05). Advanced T stage and positive N stage emerged as worse predictors of PCSS (P < 0.05). Advanced age, T stage, and positive N stage were the only factors that were significantly associated with worse OS (P < 0.05). The 5-year cumulative incidence rate of grade ≥ 2 late GU and GI toxicity was 17.8% (95% CI 12.5-22.7%) and 23.4% (95% CI 17.7-28.7%), respectively. CONCLUSIONS: Moderately hypofractionated radiotherapy (67.5 Gy in 25 fractions) for this predominantly high-risk, locally advanced, or N1 in Chinese patients demonstrates encouraging long-term outcomes and acceptable toxicity. This fractionation schedule deserves further evaluation in similar populations.

Radiation-Induced Lymphopenia Predicts Poorer Prognosis in Patients With Breast Cancer: A Post Hoc Analysis of a Randomized Controlled Trial of Postmastectomy Hypofractionated Radiation Therapy.

PURPOSE: The aim of this study was to determine whether radiation-induced lymphopenia affects the survival of patients with breast cancer. METHODS AND MATERIALS: Post hoc analysis was conducted on data from 598 patients with breast cancer from a randomized controlled trial comparing postmastectomy hypofractionated radiation therapy (HFRT; 43.5 Gy in 15 fractions over 3 weeks) with conventional fractionated radiation therapy (CFRT; 50 Gy in 25 fractions over 5 weeks). Mean peripheral lymphocyte count (PLC) at different time points in the 2 groups was compared by the t test. Disease-free survival and overall survival were analyzed by the Kaplan-Meier method and compared between groups by the log-rank test. RESULTS: Baseline PLC (pre-PLC) was comparable between HFRT and CFRT patients (1.60 ± 0.57 × 109/L vs 1.56 ± 0.52 × 109/L; P = .33). In both groups, the PLC declined steadily during the course of radiation therapy but started to recover at 1 month after radiation therapy. Incidence of lymphopenia was significantly lower in HFRT patients (45.4% vs 55.7%; P = .01). Nadir-PLC was significantly higher in HFRT patients (1.08 ± 0.37 × 109/L vs 0.97 ± 0.31× 109/L; P < .001), as was the nadir-PLC/pre-PLC ratio (0.72 ± 0.28 vs 0.67 ± 0.28; P = .02). Median follow-up was 57.6 months (interquartile range, 38.5-81.4). The 5-year disease-free survival was significantly lower in patients with a nadir-PLC/pre-PLC ratio <0.8 than in those with a ratio ≥0.8 (71.8% vs 82.6%; P = .01); however, overall survival was comparable between the groups (85.8% vs 90.6%; P = .24). CONCLUSIONS: The risk of radiation-induced lymphopenia in patients with breast cancer is lower with HFRT than with CFRT. A low nadir-PLC/pre-PLC ratio may predict poor prognosis.

SRY-related high-mobility-group box 4: Crucial regulators of the EMT in cancer.

The epithelial-mesenchymal transition (EMT) is a process of cell transformation under certain physiological and pathological states in which epithelial cells are transformed into mesenchymal cells with fibroblast-like properties, which confers upon them the increased invasion and migration capabilities of cancer cells. Previous studies have demonstrated that SRY-related high-mobility-group box 4 (Sox4) protein coordinates EMT-related pathways and EMT-related transcription factors, thereby regulating the EMT process. The focus of this review is to evaluate recent advances regarding the role of Sox4 protein in the cancer EMT. First, we provide an overview of the general background of Sox4 (structure and function) and the EMT in cancer. Next, we introduce the interactions between Sox4 protein and various factors during cancer EMT. Finally, we suggest directions for future investigations. In general, the information compiled in this paper should serve as a comprehensive repository of information on the subject matter and contribute to the design of other research and future efforts to develop therapeutic strategies that target the Sox4 protein.

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis.

Atherosclerosis is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases and has attracted more attention in recent years. Multiple studies have demonstrated that the signal transducer and activator of transcription 3 (STAT3) plays essential roles in the process of atherosclerosis. Moreover, aberrant STAT3 activation has been shown to contribute to the occurrence and development of atherosclerosis. Therefore, the study of STAT3 inhibitors has gradually become a focal research topic. In this review, we describe the crucial roles of STAT3 in endothelial cell dysfunction, macrophage polarization, inflammation, and immunity during atherosclerosis. STAT3 in mitochondria is mentioned as well. Then, we present a summary and classification of STAT3 inhibitors, which could offer potential treatment strategies for atherosclerosis. Furthermore, we enumerate some of the problems that have interfered with the development of mature therapies utilizing STAT3 inhibitors to treat atherosclerosis. Finally, we propose ideas that may help to solve these problems to some extent. Collectively, this review may be useful for developing future STAT3 inhibitor therapies for atherosclerosis.

Mechanisms explaining the efficacy of psoralidin in cancer and osteoporosis, a review.

Psoralidin (PSO) is a natural phenolic coumarin that is extracted from the seeds of Psoralea corylifolia L. PSO possesses a variety of pharmacological activities, including anti-oxidative, antibacterial, anti-inflammatory, anti-depressive and estrogenic-like effects. Other studies have indicated that PSO plays a beneficial role in multiple disease, especially cancer and osteoporosis. In this review, we first outline the basic background of PSO. Then we introduced the molecular mechanisms and signaling pathways of PSO in multiple cancers to elucidate its anticancer potential via inducing oxidative stress and apoptosis, inhibiting proliferation, promoting autophagy-dependent cell death, and activating the estrogen receptors (ER)-signaling pathway. Finally, we recommend the direction of future investigations. In general, the information compiled in this paper should serve as a comprehensive repository of information to help design PSO in other research and future efforts.

Comparison of outcome and toxicity of postoperative intensity-modulated radiation therapy with two-dimensional radiotherapy in patients with soft tissue sarcoma of extremities and trunk.

BACKGROUND: To compare the survival outcomes and late toxicities of postoperative intensity-modulated radiation therapy (IMRT) with two-dimensional radiotherapy (2D-RT) for patients with soft tissue sarcoma (STS) of extremities and trunk. METHODS: 274 consecutive patients with nonmetastatic STS of extremities and trunk treated with postoperative IMRT (n = 187) and 2D-RT (n = 87) were analyzed. Survival was calculated by using Kaplan-Meier method. Independent prognostic factors were identified using Cox stepwise regression analysis for variables with a P-value <0.1 in univariate analysis. RESULTS: With a median follow-up time of 58.1 months, 30 local recurrences, 66 distant metastases, and 40 deaths occurred. Compared to 2D-RT group, the IMRT group had higher 5-year local recurrence-free survival (LRFS) (91.1% vs 80.8%; P = 0.029), distant metastasis-free survival (DMFS) (80.0% vs 69.7%; P = 0.048), disease-free survival (DFS) (75.2% vs 59.2%; P = 0.021), and overall survival (OS) (90.2% vs 81.0%; P = 0.029). Multivariate analysis showed IMRT was an independent favorable factor for LRFS, DMFS, DFS, and OS. For late toxicities, the patients in IMRT group enjoyed lower incidences of ≥Grade 2 joint stiffness (3.9% vs 12.3%; P = 0.041) and ≥Grade 3 fractures (0.0% vs 3.4%; P = 0.25) than those in 2D-RT group. ≥Grade 2 Edema was similar between these two groups (4.8% vs 9.2%; P = 0.183). CONCLUSIONS: When compared with conventional techniques, postoperative IMRT seems to provide better LRFS, DMFS, DFS, and OS and less late toxicities in patients with STS of extremities and trunk, which should be offered as a preferred treatment.

Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial.

BACKGROUND: To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. METHODS: This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962. FINDINGS: Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2-81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8-10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4-10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI -3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001). INTERPRETATION: Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients. FUNDING: National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.