A novel narrow surface cage for full endoscopic oblique lateral lumbar interbody fusion: A finite element study.

OBJECTIVE: To evaluate the mechanical response of a narrow surface cage that we designed for full endoscopic oblique lateral lumbar interbody fusion (FE-OL-LIF). METHODS: A finite element (FE) model of lumbar spine was developed and validated. To simulate the FE-OL-LIF, the functional spinal unit (FSU) L4-L5 was assembled with a narrow surface polyetheretherketone (PEEK) cage, two rods and four screws. 500N load combined with 7.5Nm moment was applied to the surgical models. Effect of the cage width on the stress was studied. RESULTS: Range of motion (ROM) in the surgical models significantly decreased by 88% in flexion, 91% extension, 85% in right and left lateral bending, 75% in right and left axial rotation as compared to the intact model. Width of the cage slightly decreased the ROM in all loading scenarios. Flexion produced the highest stress in the cages and endplates. In all loading cases, the maximum stresses of cages and endplates were both lower than their yield stress. CONCLUSIONS: In engineering analysis, the novel narrow-surface cage had a strength to support spine activities. 9 mm width cage was recommended in FE-OL-LIF. This study provided engineering evidence and technical advice to improve the design of minimally invasive cage. Fatigue test and cadaver trial shall be improved.

Low-Dose Arsenic Trioxide Modulates the Differentiation of Mouse Embryonic Stem Cells.

Arsenic (As) is a well-known environmental pollutant, while arsenic trioxide (ATO) has been proven to be an effective treatment for acute promyelocytic leukemia, however, the mechanism underlying its dual effects is not fully understood. Embryonic stem cells (ESCs) exhibit properties of stemness and serve as a popular model to investigate epigenetic modifiers including environmental pollutants. Herein, the effects of low-dose ATO on differentiation were evaluated in vitro using a mouse ESCs (mESCs) cell line, CGR8. Cells treated with 0.2-0.5 µM ATO for 3-4 days had slight inhibition of proliferation with elevation of apoptosis, but obvious alterations of differentiation by morphological checking and alkaline phosphatase (AP) staining. Moreover, ATO exposure significantly decreased the mRNA expression of the stemness maintenance genes including Oct4, Nanog, and Rex-1 ( P < 0.01), whereas obviously increased some tissue-specific differentiation marker genes such as Gata4, Gata-6, AFP, and IHH. These alterations were consistent with the differentiation phenotype induced by retinoic acid (RA) and the expression patterns of distinct pluripotency markers such as SSEA-1 and Oct4. Furthermore, low-dose ATO led to a quantitative increase in Caspase 3 (CASP3) activation and subsequent cleavage of Nanog around 27 kDa, which corresponded with the mouse Nanog cleaved by CASP3 in a tube cleavage assay. Taken together, we suggest that low-dose ATO exposure will induce differentiation, other than apoptosis, of ESCs, such effects might be tuned partially by ATO-induced CASP3 activation and Nanog cleavage coupling with other differentiation related genes involved. The present findings provide a preliminary action mechanism of arsenic on the cell fate determination.

Design of mulitlevel OLF approach ("V"-shaped decompressive laminoplasty) based on 3D printing technology.

PURPOSE: To introduce a new surgical approach to the multilevel ossification of the ligamentum flavum (OLF) aided by three-dimensional (3D) printing technology. METHODS: A multilevel OLF patient (male, 66 years) was scanned using computed tomography (CT). His saved DICOM format data were inputted to the Mimics14.0 3D reconstruction software (Materialise, Belgium). The resulting 3D model was used to observe the anatomical features of the multilevel OLF area and to design the surgical approach. At the base of the spinous process, two channels were created using an osteotomy bilaterally to create a "V" shape to remove the bone ligamentous complex (BLC). The decompressive laminoplasty using mini-plate fixation was simulated with the computer. The physical model was manufactured using 3D printing technology. The patient was subsequently treated using the designed surgery. RESULT: The operation was completed successfully without any complications. The operative time was 90 min, and blood loss was 200 ml. One month after the operation, neurologic function was recovered well, and the JOA score was improved from 6 preoperatively to 10. Postoperative CT scanning showed that the OLF was totally removed, and the replanted BLC had not subsided. CONCLUSION: 3D printing technology is an effective, reliable, and minimally invasive method to design operations. The technique can be an option for multilevel OLF surgical treatment. This can provide sufficient decompression with minimum damage to the spine and other intact anatomical structures.

Selenium nanoparticles decorated with Ulva lactuca polysaccharide potentially attenuate colitis by inhibiting NF-κB mediated hyper inflammation.

BACKGROUND: Selenium (Se) is an essential micronutrient trace element and an established nutritional antioxidant. Low Se status exacerbates inflammatory bowel diseases progression, which involves hyper inflammation in the digestive tract. Se nanoparticles (SeNPs) exhibit anti-inflammatory activity accompanied by low toxicity, especially when decorated with natural biological compounds. Herein, we explored the beneficial effects of SeNPs decorated with Ulva lactuca polysaccharide (ULP) in mice subjected to the acute colitis model. RESULTS: We constructed SeNPs coated with ULP (ULP-SeNPs) in average diameter ~130 nm and demonstrated their stability and homogeneity. Supplementation with ULP-SeNPs (0.8 ppm Se) resulted in a significant protective effect on DSS-induced acute colitis in mice including mitigation of body weight loss, and colonic inflammatory damage. ULP-SeNPs ameliorated macrophage infiltration as evidenced by decreased CD68 levels in colon tissue sections. The anti-inflammatory effects of ULP-SeNPs were found to involve modulation of cytokines including IL-6 and TNF-α. Mechanistically, ULP-SeNPs inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which drives the transcription of these pro-inflammatory cytokines. CONCLUSIONS: ULP-SeNPs supplementation may offer therapeutic potential for reducing the symptoms of acute colitis through its anti-inflammatory actions.

Does a deep seated L5 vertebra position with respect to the iliac crests affect the accuracy of percutaneous pedicle screw placement at lumbosacral junction?

BACKGROUND: Significant prominence of iliac crests with a deep seated L5 vertebra can potentially interfere with the screw trajectory when placing percutaneous pedicle screws (PPS) at the lumbosacral segment. The objective of this study was to investigate the influence of L5 position in relation to the iliac crests on the accuracy of percutaneous placement of lumbosacral pedicle screws. METHODS: From Oct 2012 to Sep 2014, 54 patients who underwent PPS placement at L5-S1 segment were recruited. Patients were divided into 2 groups: the L5-Seated Group (L5-S Group, n = 34) including patients with intercrest lines passing through the L4 vertebra or L4/5 intervertebral disc; whereas the L5-Non-Seated Group (L5-NS Group, n = 20) including patients with intercrest lines passing through the L5 vertebra. Postoperative computerized tomography was obtained in all patients, and PPS accuracy was evaluated by grading pedicle breach (Grade 0, no breach; Grade 1, ≤2mm; Grade 2, >2mm without neurological compromise; Grade 3, with complications). Screw convergence angle (SCA), defined as the angle subtended by the screw axis and vertebral midline, was also recorded. RESULTS: In the L5-S Group, 82.4% (56/68) screws were measured as Grade 0 at L5, and 66.2% (45/68) were Grade 0 at S1; meanwhile, in the L5-NS Group, 77.5% (31/40) and 75.0% (30/40) screws were Grade 0 at L5 and S1, respectively. Misplacement rate was numerically higher at S1 in the L5-S Group (P > 0.05). There were significantly more medial pedicle violations at S1 in the L5-S Group as compared to the L5-NS Group (25.0% vs 7.5%, P = 0.024). No statistical difference was found in L5 SCA between the 2 groups (L5-S Group 23.7° ± 7.4° vs L5-NS Group 23.4° ± 10.6°, P = 0.945); however, S1 SCA was significantly smaller in the L5-S Group (14.7° ± 5.8°) when compared with the L5-NS Group (20.8° ± 5.2°) (P = 0.036). CONCLUSIONS: A deep seated L5 vertebra with respect to the iliac crests might compromise the accuracy of PPS placement at S1 vertebra. Severe iliac prominence may interfere with the screw trajectory and limit the medial angulation of pedicle screw for percutaneous S1 fixation.

Extensive spinal epidural abscess due to Streptococcus intermedius: a case report treated conservatively and literature review.

Purpose: To describe the clinical significance of prompt, adequate, and targeted intravenous antibiotic (IV antibiotic) therapy in the successful management of spinal epidural abscess (SEA) associated with Streptococcus intermedius (S. intermedius) infection. Case description: SEA is a rare, but catastrophic infection that may result in a high risk of permanent neurological disability. A 52-year-old Chinese female patient was presented to the emergency department due to 2 years of low back pain and 3 days of decreased muscle strength in the extremities. The blood culture confirmed the presence of S. intermedius infection, and gadolinium-enhanced magnetic resonance imaging (MRI) demonstrated widespread epidural abscesses in the cervical, thoracic, and lumbar spine canal. Empirical IV antibiotic therapy with vancomycin was promptly initiated, with meropenem and moxifloxacin added subsequently based on blood culture results. After 5 days of IV antibiotic treatment, the patient's blood culture became negative. 6 weeks later, a follow-up MRI showed a decrease in the size of the abscess. The patient's muscle strength was mostly restored after 2 months of IV antibiotic treatment. Conclusion: Repeat examinations or gadolinium-enhanced MRI should be considered when initial MRI findings are not diagnostic of SEA. For extensive SEA caused by Streptococcus intermedius infection, surgery may be non-essential, and the judicious antibiotic selection and adequate treatment duration are pivotal for successful conservative management. Furthermore, for patients who are not amenable to surgery, a comprehensive evaluation of their condition and meticulous implementation of a precise pharmacological regimen holds noteworthy clinical significance.

Biomechanical evaluation of a novel anterior transpedicular screw-plate system for anterior cervical corpectomy and fusion (ACCF): a finite element analysis.

Background and objective: Cervical fusion with vertebral body screw (VBS)-plate systems frequently results in limited biomechanical stability. To address this issue, anterior transpedicular screw (ATPS) fixation has been developed and applied preliminarily to multilevel spinal fusion, osteoporosis, and three-column injury of the cervical spine. This study aimed to compare the biomechanical differences between unilateral ATPS (UATPS), bilateral ATPS (BATPS), and VBS fixation using finite element analysis. Materials and methods: A C6 corpectomy model was performed and a titanium mesh cage (TMC) and bone were implanted, followed by implantation of a novel ATPS-plate system into C5 and C7 to simulate internal fixation with UATPS, BATPS, and VBS. Internal fixation with UATPS comprises ipsilateral transpedicular screw-contralateral vertebral body screw (ITPS-CVBS) and cross transpedicular screw-vertebral body screw (CTPS-VBS) fixations. Mobility, the maximal von Mises stress on TMC, the stress distribution and maximal von Mises stress on the screws, and the maximum displacement of the screw were compared between the four groups. Results: Compared with the original model, each group had a reduced range of motion (ROM) under six loads. After ACCF, the stress was predominantly concentrated at two-thirds of the length from the tail of the screw, and it was higher on ATPS than on VBS. The stress of the ATPS from the cranial part was higher than that of the caudal part. The similar effect happened on VBS. The screw stress cloud maps did not show any red areas reflective of a concentration of the stress on VBS. Compared with VBS, ATPS can bear a greater stress from cervical spine movements, thus reducing the stress on TMC. The maximal von Mises stress was the lowest with bilateral transpedicular TMC and increased with cross ATPS and with ipsilateral ATPS. ITPS-CVBS, CTPS-VBS, and BATPS exhibited a reduction of 2.3%-22.1%, 11.9%-2.7%, and 37.9%-64.1% in the maximum displacement of screws, respectively, compared with that of VBS. Conclusion: In FEA, the comprehensive stability ranked highest for BATPS, followed by CTPS-VBS and ITPS-CVBS, with VBS demonstrating the lowest stability. Notably, utilizing ATPS for fixation has the potential to reduce the occurrence of internal fixation device loosening after ACCF when compared to VBS.

Percutaneous Bilateral Endoscopic Lumbar Interbody Fusion: Technical Note and Preliminary Results.

Objective: The purpose of this study was to investigate the feasibility and clinical efficacy of the percutaneous bilateral endoscopy technique (microendoscopic trans-Kambin's triangle lumbar interbody fusion + percutaneous endoscopic transforaminal decompression of the lumbar spinal canal, ME-TKT-LIF+ PETD) in the treatment of lumbar degenerative diseases. Methods: From May 2016 to September 2018, 29 patients (16 males and 13 females) who suffered from neurologic symptoms due to degenerative lumbar spine disease and underwent percutaneous bilateral endoscopy technique were enrolled. A microendoscope was used for fusion, and a percutaneous endoscope was used for spinal canal decompression. These patients' perioperative and clinical outcome-related parameters were collected and analyzed. Results: The mean intraoperative blood loss was 72.8 ± 40.6 ml, the operation time was 87.1 ± 10.1 min, the postoperative ambulatory time was 1.69 ± 1.0 days, the hospital stay was 2.6 ± 1.3 days, and the follow-up period was 22.34 ± 4.2 months. The visual analog scale (VAS) and the Oswestry disability index (ODI) were significantly improved at the early postoperative and last follow-up, respectively. According to the modified MacNab criteria, 11 (11/29) cases were rated as excellent, 15 (15/29) as good, and 3 (3/29) as fair, and the excellent and good rate was 89.7%. Twenty-eight (28/29) cases demonstrated solid fusion, and the fusion rate was 96.6%. Conclusion: The percutaneous bilateral endoscopy technique is safe and feasible in the treatment of lumbar degenerative diseases, with the advantage that more normal anatomical structures are preserved. It is an optional method of lumbar interbody fusion.

Arsenic retention in erythrocytes and excessive erythrophagocytosis is related to low selenium status by impaired redox homeostasis.

Arsenic (As) contamination in drinking water is a global public health problem. Epidemiological studies have shown that selenium (Se) deficiency is associated with an increasing risk of arsenism. However, the association between Se status and As retention in erythrocytes and mechanisms underlying this association have not been fully investigated. In the present study, a total of 165 eligible subjects were recruited and As was found to accumulate in blood mainly by retention in erythrocytes. Retention of As in erythrocytes was negatively correlated with Se status, antioxidant parameters related to Se and As methylation capacity, but positively correlated with the protein-binding capacity of As. Additionally, erythrocytes isolated from subjects with low Se status exhibited cellular damage along with lower protein levels of CD47, which could be aggravated by hydrogen peroxide treatment. Consistent with the human study, the erythrocytes from mice with sub-chronic As exposure exhibited similar cellular damage and shown to be phagocytosed by splenic macrophages, and these effects were mitigated by dietary Se supplementation. Furthermore, hydrogen peroxide treatment induced excessive phagocytosis of erythrocytes with As exposure by splenic macrophages, while co-treating erythrocytes with the reducing agent, N-Acetyl-l-cysteine, mitigated this excessive erythrophagocytosis. Hyperactivation of the NFκB pathway was also detected in splenic macrophages after excessive erythrophagocytosis. In conclusion, this study found that low Se status involving impaired redox homeostasis increased As retention in erythrocytes, which were subsequently phagocytosed by splenic macrophages and led to an increased inflammatory status of splenic macrophages. These findings provide insight into physiological features of arsenism related to Se status and redox homeostasis.

Screws Fixation for Oblique Lateral Lumbar Interbody Fusion (OL-LIF): A Finite Element Study.

BACKGROUND: The combination of screw fixation and cage can provide stability in lumbar interbody fusion (LIF), which is an important technique to treat lumbar degeneration diseases. As the narrow surface cage is developed in oblique lateral lumbar interbody fusion (OL-LIF), screw fixation should be improved at the same time. We used the finite element (FE) method to investigate the biomechanics response by three different ways of screw fixation in OL-LIF. METHODS: Using a validated FE model, OL-LIF with 3 different screw fixations was simulated, including percutaneous transverterbral screw (PTVS) fixation, percutaneous cortical bone trajectory screw (PCBTS) fixation, and percutaneous transpedical screw (PPS) fixation. Range of motion (ROM), vertebral body displacement, cage displacement, cage stress, cortical bone stress, and screw stress were compared. RESULTS: ROM in FE models significantly decreased by 84-89% in flexion, 91-93% in extension, 78-89% in right and left lateral bending, and 73-82% in right and left axial rotation compared to the original model. The maximum displacement of the vertebral body and the cage in six motions except for the extension of model PTVS was the smallest among models. Meanwhile, the model PTVS had the higher stress of screw-rods system and also the lowest stress of cage. In all moments, the maximum stresses of the cages were lower than their yield stress. CONCLUSIONS: Three screw fixations can highly restrict the surgical functional spinal unit (FSU). PTVS provided the better stability than the other two screw fixations. It may be a good choice for OL-LIF.

Author Correction: Methylseleninic Acid Provided at Nutritional Selenium Levels Inhibits Angiogenesis by Down-regulating Integrin ß3 Signaling.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Use of a Mouse Model and Human Umbilical Vein Endothelial Cells to Investigate the Effect of Arsenic Exposure on Vascular Endothelial Function and the Associated Role of Calpains.

BACKGROUND: Arsenic (As) is a well-known environmental contaminant. Chronic exposure to As is known to increase the risk of cardiovascular diseases, including atherosclerosis, hypertension, diabetes, and stroke. However, the detailed mechanisms by which As causes vascular dysfunction involving endothelial integrity and permeability is unclear. OBJECTIVES: Our goal was to investigate how exposure to As leads to endothelial dysfunction. METHODS: Arsenic trioxide (ATO) was used to investigate the effects and mechanisms by which exposure to As leads to endothelial dysfunction using a mouse model and cultured endothelial cell monolayers. RESULTS: Compared with the controls, mice exposed chronically to As (10 ppb in drinking water supplied by ATO) exhibited greater vascular permeability to Evans blue dye and fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA). In addition, endothelial monolayers treated with ATO ([Formula: see text] As) exhibited greater intracellular gaps and permeability to low-density lipoprotein or transmigrating THP-1 cells. Furthermore, activity and protein levels of calpain-1 (CAPN-1) were significantly higher in aortas and human umbilical vein endothelial cells (HUVECs) treated with ATO. These results were consistent with effects of ATO treatment and included a rapid increase of intracellular calcium ([Formula: see text]) and higher levels of CAPN-1 in the plasma membrane. Endothelial cell dysfunction and the proteolytic disorganization of vascular endothelial cadherin (VE-cadherin) in HUVECs in response to ATO were partially mitigated by treatment with a CAPN-1 inhibitor (ALLM) but not a CAPN-2 inhibitor (Z-LLY-FMK). CONCLUSIONS: This study found that in mice and HUVEC models, exposure to ATO led to CAPN-1 activation by increasing [Formula: see text] and CAPN-1 translocation to the plasma membrane. The study also suggested that inhibitor treatment may have a role in preventing the vascular endothelial dysfunction associated with As exposure. The findings presented herein suggest that As-induced endothelial dysfunction involves the hyperactivation of the CAPN proteolytic system. https://doi.org/10.1289/EHP4538.

Scalable Generation of Mesenchymal Stem Cells from Human Embryonic Stem Cells in 3D.

Human embryonic stem cell (hESC) derived mesenchymal stem cells (EMSC) are efficacious in treating a series of autoimmune, inflammatory, and degenerative diseases in animal models. However, all the EMSC derivation methods reported so far rely on two-dimensional (2D) culture systems, which are inefficient, costive and difficult for large-scale production. HESC, as an unlimited source, can be successively propagated in spheroids. Here, we demonstrate that hESC spheroids can directly differentiate into MSC spheroids (EMSCSp) within 20 days in one vessel without passaging and the system is scalable to any desired size. EMSCSp can further differentiate into osteocytes and chondrocytes in spheres or demineralized bone matrix. EMSCSp also retains immune-modulatory effects in vitro and therapeutic effects on two mouse models of colitis after dissociation. Compared to EMSC differentiated in monolayer, EMSCSp-derived cells have faster proliferation and higher yield and develop less apoptosis and slower senescence. Thus, the 3D differentiation system allows simple, cost-effective, and scalable production of high-quality EMSC and subsequently bone and cartilage tissues for therapeutic application.

Application of a narrow-surface cage in full endoscopic minimally invasive transforaminal lumbar interbody fusion.

BACKGROUND: Spinal endoscopy has been widely applied in lumbar discectomy and decompression. However, endoscopic lumbar interbody fusion still remains a technical challenge due to the limited space within the working trocar for cage implantation. The purpose of this study was to investigate the feasibility and effectiveness of using a narrow-surface fusion cage in full endoscopic minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of lumbar degenerative disease. MATERIALS AND METHODS: From Jun 2013 to Dec 2014, a total of 42 patients (23 males, 19 females) underwent full endoscopic MIS-TLIF at our hospital was recruited. An 8-mm-wide narrow-surface fusion cage was selected for all cases. Perioperative parameters and complications were recorded. Comparisons on visual analog scale (VAS) and oswestry disability index (ODI) scores before and after surgery were performed. At the last follow-up, Nakai grading system was applied to assess patients' satisfaction; meanwhile, interbody fusion was evaluated by computed tomography. RESULTS: Mean operation time was 233.1 ± 69.5 min, and mean blood loss during surgery was 221.8 ± 98.5 ml. Two patients (4.8%) developed neurological complications. Postoperative follow-up ranged from 24 to 36 months (mean 27.6 ± 3.8 months). VAS and ODI scores were significantly improved 3 months after surgery and at the final follow-up, respectively (P < 0.05). Outcome of surgery was graded as excellent for 32 patients, good for 8 patients, and acceptable for 2 patients, corresponding to a success rate ("good" and "excellent") of 95.2%. Thirty-nine of the 42 patients demonstrated solid interbody fusion at the last follow-up, indicating a fusion rate of 92.9%. CONCLUSION: Application of a narrow-surface fusion cage in full endoscopic MIS-TLIF for the treatment of lumbar degenerative disease is feasible and effective. The clinical outcome and fusion success of this procedure were acceptable and promising.

Reliability analysis of Cobb measurement in degenerative lumbar scoliosis using endplate versus pedicle as bony landmarks.

OBJECTIVES: Degenerative changes of endplates in older patients and tilting of vertebral body in lumbosacral lordosis could make an accurate identification of endplates for the Cobb measurement difficult. Pedicles have been proposed as alternative landmarks because they are usually better visualized, and offer similar clinical validity to the endplates. The objective of this study was to investigate the reliability of the pedicle method of Cobb measurement in degenerative lumbar scoliosis and compare it with the traditional endplate method. METHODS: Two hundred and eighty-four radiographs of degenerative lumbar scoliosis were evaluated. The radiographs were classified into groups based on the patient's age (< 60 years, 60 to 80 years, and > 80 years), level of lower end vertebra (LEV) (LEV at L5, and LEV at or above L4), and curve severity (< 20°, 20° to 40°, and > 40°). Three observers independently measured the radiographs using the endplate and pedicle methods twice with an interval of 1 week. The intra- and interobserver reliabilities were calculated using intraclass correlation coefficients (ICC). RESULTS: The intra- and interobserver ICC values were better for all observers in the > 80 years age group using the pedicle method. The intraobserver ICC values of pedicle method were also better in the LEV at L5 group, and the interobserver ICC values showed a slightly better consistency with the pedicle method. For patients with > 40° curves, the intraobserver ICC values for all observers as well as interobserver ICC values were better using the endplate method. CONCLUSION: The reliabilities of the endplate and pedicle methods for degenerative lumbar scoliosis were both excellent. The pedicle method might be better in older patients (> 80 years) and those with LEV at L5; while the endplate method could have some strength in severe cases (> 40°).

Methylseleninic Acid Provided at Nutritional Selenium Levels Inhibits Angiogenesis by Down-regulating Integrin ß3 Signaling.

Targeting angiogenesis has emerged as a promising strategy for cancer treatment. Methylseleninic acid (MSA) is a metabolite of selenium (Se) in animal cells that exhibits anti-oxidative and anti-cancer activities at levels exceeding Se nutritional requirements. However, it remains unclear whether MSA exerts its effects on cancer prevention by influencing angiogenesis within Se nutritional levels. Herein, we demonstrate that MSA inhibited angiogenesis at 2 µM, which falls in the range of moderate Se nutritional status. We found that MSA treatments at 2 µM increased cell adherence, while inhibiting cell migration and tube formation of HUVECs in vitro. Moreover, MSA effectively inhibited the sprouts of mouse aortic rings and neoangiogenesis in chick embryo chorioallantoic membrane. We also found that MSA down-regulated integrin ß3 at the levels of mRNA and protein, and disrupted clustering of integrin ß3 on the cell surface. Additionally, results showed that MSA inhibited the phosphorylation of AKT, IκBα, and NFκB. Overall, our results suggest that exogenous MSA inhibited angiogenesis at nutritional Se levels not only by down-regulating the expression of integrin ß3 but also by disorganizing the clustering of integrin ß3, which further inhibited the phosphorylation involving AKT, IκBα, NFκB. These findings provide novel mechanistic insight into the function of MSA for regulating angiogenesis and suggest that MSA could be a potential candidate or adjuvant for anti-tumor therapy in clinical settings.

Selenium-Containing Phycocyanin from Se-Enriched Spirulina platensis Reduces Inflammation in Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Activation.

Selenium (Se) plays an important role in fine-tuning immune responses. Inflammatory bowel disease (IBD) involves hyperresponsive immunity of the digestive tract, and a low Se level might aggravate IBD progression; however, the beneficial effects of natural Se-enriched diets on IBD remain unknown. Previously, we developed high-yield Se-enriched Spirulina platensis (Se-SP) as an excellent organic nutritional Se source. Here we prepared Se-containing phycocyanin (Se-PC) from Se-SP and observed that Se-PC administration effectively reduced the extent of colitis in mouse induced by dextran sulfate sodium. Supplementation with Se-PC resulted in significant protective effects, including mitigation of body weight loss, bloody diarrhea, and colonic inflammatory damage. The anti-inflammatory effects of Se-PC supplementation were found to involve modulation of cytokines, including IL-6, TNF-α, MCP-1, and IL-10. Mechanistically, Se-PC inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which is involved in the transcription of these pro-inflammatory cytokines. These results together suggest potential benefits of Se-PC as a functional Se supplement to reduce the symptoms of IBD.