TNFα and IFNγ cooperate for efficient pro- to anti-inflammatory transition of macrophages during muscle regeneration.

IFNγ is traditionally known as a proinflammatory cytokine with diverse roles in antimicrobial and antitumor immunity. Yet, findings regarding its sources and functions during the regeneration process following a sterile injury are conflicting. Here, we show that natural killer (NK) cells are the main source of IFNγ in regenerating muscle. Beyond this cell population, IFNγ production is limited to a small population of T cells. We further show that NK cells do not play a major role in muscle regeneration following an acute injury or in dystrophic mice. Surprisingly, the absence of IFNγ per se also has no effect on muscle regeneration following an acute injury. However, the role of IFNγ is partially unmasked when TNFα is also neutralized, suggesting a compensatory mechanism. Using transgenic mice, we showed that conditional inhibition of IFNGR1 signaling in muscle stem cells or fibro-adipogenic progenitors does not play a major role in muscle regeneration. In contrast to common belief, we found that IFNγ is not present in the early inflammatory phase of the regeneration process but rather peaks when macrophages are acquiring an anti-inflammatory phenotype. Further transcriptomic analysis suggests that IFNγ cooperates with TNFα to regulate the transition of macrophages from pro- to anti-inflammatory states. The absence of the cooperative effect of these cytokines on macrophages, however, does not result in significant regeneration impairment likely due to the presence of other compensatory mechanisms. Our findings support the arising view of IFNγ as a pleiotropic inflammatory regulator rather than an inducer of the inflammatory response.

Revealing the diversity of Jojoba-associated fungi using amplicon metagenome approach and assessing the in vitro biocontrol activity of its cultivable community.

Jojoba shrubs are wild plants cultivated in arid and semiarid lands and characterized by tolerance to drought, salinity, and high temperatures. Fungi associated with such plants may be attributed to the tolerance of host plants against biotic stress in addition to the promotion of plant growth. Previous studies showed the importance of jojoba as jojoba oil in the agricultural field; however, no prior study discussed the role of jojoba-associated fungi (JAF) in reflecting plant health and the possibility of using JAF in biocontrol. Here, the culture-independent and culture-dependent approaches were performed to study the diversity of the jojoba-associated fungi. Then, the cultivable fungi were evaluated for in-vitro antagonistic activity and in vitro plant growth promotion assays. The metagenome analysis revealed the existence of four fungal phyla: Ascomycota, Aphelidiomycota, Basidiomycota, and Mortierellomycota. The phylum Ascomycota was the most common and had the highest relative abundance in soil, root, branch, and fruit samples (59.7%, 50.7%, 49.8%, and 52.4%, respectively). Alternaria was the most abundant genus in aboveground tissues: branch (43.7%) and fruit (32.1%), while the genus Discosia had the highest abundance in the underground samples: soil (24%) and root (30.7%). For the culture-dependent method, a total of 14 fungi were isolated, identified, and screened for their chitinolytic and antagonist activity against three phytopathogenic fungi (Fusarium oxysporum, Alternaria alternata and Rhizoctonia solani) as well as their in vitro plant growth promotion (PGP) activity. Based on ITS sequence analysis, the selected potent isolates were identified as Aspergillus stellatusEJ-JFF3, Aspergillus flavus EJ-JFF4, Stilbocrea sp. EJ-JLF1, Fusarium solani EJ-JRF3, and Amesia atrobrunneaEJ-JSF4. The endophyte strain A. flavus EJ-JFF4 exhibited the highest chitinolytic activity (9 Enzyme Index) and antagonistic potential against Fusarium oxysporum, Alternaria alternata, and Rhizoctonia solani phytopathogens with inhibitory percentages of 72, 70, and 80 respectively. Also, A. flavus EJ-JFF4 had significant multiple PGP properties, including siderophore production (69.3%), phosphate solubilization (95.4 µg ml-1). The greatest production of Indol-3-Acetic Acid was belonged to A. atrobrunnea EJ-JSF4 (114.5 µg ml-1). The analysis of FUNGuild revealed the abundance of symbiotrophs over other trophic modes, and the guild of endophytes was commonly assigned in all samples. For the first time, this study uncovered fungal diversity associated with jojoba plants using a culture-independent approach and in-vitro assessed the roles of cultivable fungal strains in promoting plant growth and biocontrol. The present study indicated the significance of jojoba shrubs as a potential source of diverse fungi with high biocontrol and PGP activities.

TGF-ß-driven downregulation of the transcription factor TCF7L2 affects Wnt/ß-catenin signaling in PDGFRα+ fibroblasts.

Mesenchymal stromal cells (MSCs) are multipotent progenitors essential for organogenesis, tissue homeostasis, regeneration and scar formation. Tissue injury upregulates transforming growth factor ß (TGF-ß) signaling, which modulates myofibroblast fate, extracellular matrix remodeling and fibrosis. However, the molecular determinants of MSC differentiation and survival remain poorly understood. During canonical Wnt signaling, T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors regulate development and stemness, but the mechanisms by which injury-induced cues modulate their expression remain underexplored. Here, we studied the cell type-specific gene expression of TCF/LEF transcription factors and, more specifically, we investigated whether damage-induced TGF-ß signaling impairs the expression and function of TCF7L2 (also known as TCF4), using several models of MSCs, including skeletal muscle fibro-adipogenic progenitors. We show that TCF/LEFs are differentially expressed and that TGF-ß reduces the expression of TCF7L2 in MSCs but not in myoblasts. We also found that the ubiquitin-proteasome system regulates TCF7L2 proteostasis and participates in TGF-ß-mediated TCF7L2 protein downregulation. Finally, we show that TGF-ß requires histone deacetylase activity to repress the expression of TCF7L2. Thus, our work reports a novel interplay between TGF-ß and canonical Wnt signaling cascades in PDGFRα+ fibroblasts and suggests that this mechanism could be targeted in tissue repair and regeneration.

Cross-talk between TGF-ß and PDGFRα signaling pathways regulates the fate of stromal fibro-adipogenic progenitors.

Fibro-adipogenic progenitors (FAPs) are tissue-resident mesenchymal stromal cells (MSCs) required for proper skeletal muscle development, regeneration and maintenance. However, FAPs are also responsible for fibro-fatty scar deposition following chronic damage. We aimed to investigate the role of functional cross-talk between TGF-ß and PDGFRα signaling pathways in the fate of FAPs. Here, we show that the number of FAPs correlates with TGF-ß levels and with extracellular matrix deposition during regeneration and repair. Interestingly, the expression of PDGFRα changed dynamically in the fibroblast lineage after injury. Furthermore, PDGFRα-dependent immediate early gene expression changed during regeneration and repair. We also found that TGF-ß signaling reduces PDGFRα expression in FAPs, mouse dermal fibroblasts and in two related mesenchymal cell lines. Moreover, TGF-ß promotes myofibroblast differentiation of FAPs but inhibits their adipogenicity. Accordingly, TGF-ß impairs the expression of PDGFRα-dependent immediate early genes in a TGFBR1-dependent manner. Finally, pharmacological inhibition of PDGFRα activity with AG1296 impaired TGF-ß-induced extracellular matrix remodeling, Smad2 signaling, myofibroblast differentiation and migration of MSCs. Thus, our work establishes a functional cross-talk between TGF-ß and PDGFRα signaling pathways that is involved in regulating the biology of FAPs and/or MSCs.This article has an associated First Person interview with the first author of the paper.

RF-3192C and other polyketides from the marine endophytic Aspergillus niger ASSB4: structure assignment and bioactivity investigation.

Chemical investigation of the methanolic extract of endophytic Aspergillus niger SB4, isolated from the marine alga Laurencia obtuse, afforded the pentacyclic polyketide, RF-3192C (1), the dimeric coumarin orlandin (2), fonsecin B (3), TMC-256A1 (4), cyclo-(Leu-Ala) (5), and cerebroside A (6).The chemical structure of RF-3192C (1) is assigned herein for the first time using 1D/2D NMR and HRESI-MS. Additionally, the revision of the NMR assignments of orlandin (2) was reported herein as well. Investigation of the antimicrobial activities of isolated compounds revealed the high activity of RF-3192C (1) against Pseudomonas aeruginosa and Bacillus subtilis, and moderate activity against yeast. Moreover, an in vitro cytotoxic activity against liver (HEPG2), cervical (HELA), lung (A549), prostate (PC3), and breast (MCF7) cancer cell lines of the isolated compounds was evaluated. The isolation and taxonomical characterization of the producing fungus was reported as well.

Isolation of anticancer constituents from Cucumis prophetarum var. prophetarum through bioassay-guided fractionation.

BACKGROUND: Cucumis prophetarum var. prophetarum is used in Saudi folk medicine for treating liver disorders and grows widely between Abha and Khamis Mushait City, Saudi Arabia. METHODS: Bioassay-guided fractionation and purification were used to isolate the main active constituents of Cucumis prophetarum var. prophetarum fruits. These compounds were structurally elucidated using NMR spectroscopy, mass spectral analyses and x-ray crystallography. All fractions, sub-fractions and pure compounds were screened for their anticancer activity against six cancer cell lines. RESULTS: The greatest cytotoxic activity was found to be in the ethyl acetate fraction, resulting in the isolation of five cucurbitacin compounds [E, B, D, F-25 acetate and Hexanorcucurbitacin D]. Among the cucurbitacins that were isolated and tested cucurbitacin B and E showed potent cytotoxicity activities against all six human cancer cell lines. CONCLUSION: Human breast cancer cell lines were found to be the most sensitive to cucurbitacins. Preliminary structure activity relationship (SAR) for cytotoxic activity of Cucurbitacins against human breast cancer cell line MDA-MB-231 has been reported.

Staged bone grafting for the management of segmental long bone defects caused by trauma or infection using induced-membrane technique.

Treatment of segmental bone defects resulting from trauma or infection is extremely difficult. Bone segment transport with distraction osteogenesis and vascularized fibula transfer are the commonest used methods of treatment. Bone transport has problems with docking site. Vascularized fibula is technically demanding and hypertrophy occurs late. Induced membrane (Masquelet) technique is a relatively recent and simple treatment option consisting of two stages. A biological membrane is formed around cement spacer which is inserted in bone defect. In the second stage, the spacer is carefully removed and the membrane filled with autologous cancellous bone graft. From May 2013 to October 2015, we treated 20 patients with post-traumatic and post-infectious bone defect using Masquelet technique. There were 17 males and 3 females, with an average age of 38 years (range 12-64). The etiology of defect was open fractures in 6 cases (30%), infected non union in 11 cases (55%) and aseptic atrophic nonunion in 3 cases (15%). The mean size of bone defect after debridement was 7.2 cm. Soft tissue defect was present in 3 cases which was reconstructed. In the first stage involves thorough debridement, stabilization of the bone (either external or internal) and insertion of antibiotic cement spacer. 2nd stage was done after 4 to 8 weeks with insertion of morselized cancellous bone graft harvested from iliac bone, then tight closure done. 17 cases (85%) united, 2 cases (10%) of graft resorption and 1 case (5%) of infected graft. The time to union ranged from 4 to 11 months after 2nd stage with mean 7.4 months. In conclusion, induced membrane (Masquelet) technique is a safe, simple and reliable method for treating segmental bone defect. The major complications of this technique include infection and graft resorption.

Loss of Vascular CD34 Results in Increased Sensitivity to Lung Injury.

Survival during lung injury requires a coordinated program of damage limitation and rapid repair. CD34 is a cell surface sialomucin expressed by epithelial, vascular, and stromal cells that promotes cell adhesion, coordinates inflammatory cell recruitment, and drives angiogenesis. To test whether CD34 also orchestrates pulmonary damage and repair, we induced acute lung injury in wild-type (WT) and Cd34-/- mice by bleomycin administration. We found that Cd34-/- mice displayed severe weight loss and early mortality compared with WT controls. Despite equivalent early airway inflammation to WT mice, CD34-deficient animals developed interstitial edema and endothelial delamination, suggesting impaired endothelial function. Chimeric Cd34-/- mice reconstituted with WT hematopoietic cells exhibited early mortality compared with WT mice reconstituted with Cd34-/- cells, supporting an endothelial defect. CD34-deficient mice were also more sensitive to lung damage caused by influenza infection, showing greater weight loss and more extensive pulmonary remodeling. Together, our data suggest that CD34 plays an essential role in maintaining vascular integrity in the lung in response to chemical- and infection-induced tissue damage.

Excess Linoleic Acid Increases Collagen I/III Ratio and "Stiffens" the Heart Muscle Following High Fat Diets.

Controversy exists on the benefits versus harms of n-6 polyunsaturated fatty acids (n-6 PUFA). Although n-6 PUFA demonstrates anti-atherosclerotic properties, survival following cardiac remodeling may be compromised. We hypothesized that n-6 PUFA like linoleic acid (LA) or other downstream PUFAs like γ-linolenic acid or arachidonic acid alter the transforming growth factor-ß (TGFß)-collagen axis in the heart. Excess dietary LA increased the collagen I/III ratio in the mouse myocardium, leading to cardiac "stiffening" characterized by impaired transmitral flow indicative of early diastolic dysfunction within 5 weeks. In vitro, LA under TGFß1 stimulation increased collagen I and lysyl oxidase (LOX), the enzyme that cross-links soluble collagen resulting in deposited collagen. Overexpression of fatty acid desaturase 2 (fads2), which metabolizes LA to downstream PUFAs, reduced collagen deposits, LOX maturation, and activity with LA, whereas overexpressing fads1, unrelated to LA desaturation, did not. Furthermore, fads2 knockdown by RNAi elevated LOX activity and collagen deposits in fibroblasts with LA but not oleic acid, implying a buildup of LA for aggravating such pro-fibrotic effects. As direct incubation with γ-linolenic acid or arachidonic acid also attenuated collagen deposits and LOX activity, we concluded that LA itself, independent of other downstream PUFAs, promotes the pro-fibrotic effects of n-6 PUFA. Overall, these results attempt to reconcile opposing views of n-6 PUFA on the cardiovascular system and present evidence supporting a cardiac muscle-specific effect of n-6 PUFAs. Therefore, aggravation of the collagen I/III ratio and cardiac stiffening by excess n-6 PUFA represent a novel pathway of cardiac lipotoxicity caused by high n-6 PUFA diets.

Novel Compounds with new Anti-Ulcergenic Activity from Convolvulus pilosellifolius Using Bio-Guided Fractionation.

Oral administration of the total alcohol extract of Convolvulus pilosellifolius Desr. (250 and 500 md/kg) showed potent anti-ulcerogenic activity in absolute ethanol-induced ulcer model in rats; it showed percent protection of control ulcer by 69.2 and 84.6%, respectively, while standard ranitidine (100 mg/kg) exhibited 46.2%. Bio-guided work leads to isolation of two novel compounds (1 and 2), which were identified through 1 H, 13 C NMR, HMPC, HMQC and DEPT as: methyl 2-(hydroxymethyl) octanoate, named as amanitate, and 16-amino-9,13-dimethyl-17-(prop-1-en-2-yl)-hexadecahydro-1H-cyclopenta[a] phenanthren-3-ol, named as asmatol. Both compounds (50 mg/kg) possessed anti-ulcerogenic activity with 95.4% and 55.84% protection, respectively. Two known compounds (3 and 4) were also isolated and identified through comparison with authentic samples and confirmed through different NMR techniques as kampeferol and quercetin. These compounds also showed anti-ulcerogenic activity with 78.38% and 5.38% protection, respectively. The cytoprotective mechanism explains the potent anti-ulcerogenic activity of the total alcohol extract and the isolated compounds. The extract was highly safe as the LD50 was more than 5000 mg/kg. These results were well supported by the sub-chronic toxicity study, as the extract (500 mg/kg) administrated orally to rats for 35 consecutive days showed no alteration in the liver and kidney functions. Copyright © 2016 John Wiley & Sons, Ltd.

Partial deletion of ROCK2 protects mice from high-fat diet-induced cardiac insulin resistance and contractile dysfunction.

Obesity is associated with cardiac insulin resistance and contractile dysfunction, which contribute to the development of heart failure. The RhoA-Rho kinase (ROCK) pathway has been reported to modulate insulin resistance, but whether it is implicated in obesity-induced cardiac dysfunction is not known. To test this, wild-type (WT) and ROCK2(+/-) mice were fed normal chow or a high-fat diet (HFD) for 17 wk. Whole body insulin resistance, determined by an insulin tolerance test, was observed in HFD-WT, but not HFD-ROCK2(+/-), mice. The echocardiographically determined myocardial performance index, a measure of global systolic and diastolic function, was significantly increased in HFD-WT mice, indicating a deterioration of cardiac function. However, no change in myocardial performance index was found in hearts from HFD-ROCK2(+/-) mice. Speckle-tracking-based strain echocardiography also revealed regional impairment in left ventricular wall motion in hearts from HFD-WT, but not HFD-ROCK2(+/-), mice. Activity of ROCK1 and ROCK2 was significantly increased in hearts from HFD-WT mice, and GLUT4 expression was significantly reduced. Insulin-induced phosphorylation of insulin receptor substrate (IRS) Tyr(612), Akt, and AS160 was also impaired in these hearts, while Ser(307) phosphorylation of IRS was increased. In contrast, the increase in ROCK2, but not ROCK1, activity was prevented in hearts from HFD-ROCK2(+/-) mice, and cardiac levels of TNFα were reduced. This was associated with normalization of IRS phosphorylation, downstream insulin signaling, and GLUT4 expression. These data suggest that increased activation of ROCK2 contributes to obesity-induced cardiac dysfunction and insulin resistance and that inhibition of ROCK2 may constitute a novel approach to treat this condition.

Immunomodulation of RAW 264.7 murine macrophage functions and antioxidant activities of 11 plant extracts.

A group of 11 medicinal plants, including Lavandula pubescens, Trigonella foenugricium, Salsola schweinforthi, Calligonum comosum, Silene succulenta, Silene villosa, Bogonvillea glabra, Cakile maritime, Gomphrene celesoids, Mirabilis jalaba, and Silene nocturna growing in Egypt, were extracted and examined for their immunomodulatory and antioxidant activities. RAW 264.7 cells were recruited to investigate the immunomodulatory effect through multiple parameters analysis. First, the proliferation index of macrophages cells was evaluated revealing that Trigonella foenugricium, Silene succulenta and Silene villosa have a significant cytotoxic effect on RAW cells. Interestingly, we observed enhancement of macrophages phagocytic function of by all extracts except Cakile maritime, Gomphrena celosioides and Silene nocturna. Afterwards, macrophages were challenged by incubation with LPS and the effect of various extracts on inflammatory responses was investigated; the generation of NO from activated macrophage was substantially suppressed by 7 extracts namely, Trigonella foenugricium, Calligonum comosum, Silene succulenta, Bougainvillea glabra, Mirabilis jalaba, Gomphrena celosioides and Silene nocturna. TNF-α was decreased by percentage range from 3.8 to 85.8% and Trigonella foenugricium extract showed the highest inhibition of TNF-α release. All extracts except Trigonella foenugricium, Salsola schweinforthi, Silene succulenta and Mirabilis jalaba significantly inhibited COX-2 production from stimulated macrophage. Moreover, evaluating the potential antioxidant activity of these extracts showed that Trigonella foenugricium, Salsola schweinforthi, Calligonum comosum, Bogonvillea glabra and Mirabilis jalaba exhibited some antioxidant activities. Taken together, our results suggest that some of these extracts may have a considerable antinflammatory and antioxidant effects and may be a potential therapeutic choice in the treatment of inflammatory diseases.

Recovery of precision grasping after motor cortex lesion does not require forced use of the impaired hand in Macaca mulatta.

We investigated recovery of precision grasping of small objects between the index finger and thumb of the impaired hand without forced use after surgically placed lesions to the hand/arm areas of M1 and M1 + lateral premotor cortex in two monkeys. The unilateral lesions were contralateral to the monkey's preferred hand, which was established in prelesion testing as the hand used most often to acquire raisins in a foraging board (FB) task in which the monkey was free to use either hand to acquire treats. The lesions initially produced a clear paresis of the contralesional hand and use of only the ipsilesional hand to acquire raisins in the FB task. However, beginning about 3 weeks after the lesion both monkeys spontaneously began using the impaired contralesional hand in the FB task and increased use of that hand over the next few tests. Moreover, the monkeys clearly used precision grasp to acquire the raisins in a similar manner to prelesion performances, although grasp durations were longer. Although the monkeys used the contralesional hand more often than the ipsilesional hand in some postlesion testing sessions, they did not recover to use the hand as often as in prelesion testing when the preferred hand was used almost exclusively. These findings suggest that recovery of fine hand/digit motor function after localized damage to the lateral frontal motor areas in rhesus monkeys does not require forced use of the impaired hand.

Phytochemical and biological assessment of secondary metabolites isolated from a rhizosphere strain, Sphingomonas sanguinis DM of Datura metel.

BACKGROUND: The plant roots excrete a large number of organic compounds into the soil. The rhizosphere, a thin soil zone around the roots, is a hotspot for microbial activity, making it a crucial component of the soil ecosystem. Secondary metabolites produced by rhizospheric Sphingomonas sanguinis DM have sparked significant curiosity in investigating their possible biological impacts. METHODS: A bacterial strain has been isolated from the rhizosphere of Datura metel. The bacterium's identification, fermentation, and working up have been outlined. The ethyl acetate fraction of the propagated culture media of Sphingomonas sanguinis DM was fractioned and purified using various chromatographic techniques. The characterization of the isolated compounds was accomplished through the utilization of various spectroscopic techniques, such as UV, MS, 1D, and 2D-NMR. Furthermore, the evaluation of their antimicrobial activity was conducted using the agar well diffusion method, while cytotoxicity was assessed using the MTT test. RESULTS: The extract from Sphingomonas sanguinis DM provided two distinct compounds: n-dibutyl phthalic acid (1) and Bis (2-methyl heptyl) phthalate (2) within its ethyl acetate fraction. Furthermore, the 16S rRNA gene sequence of Sphingomonas sanguinis DM has been registered under the NCBI GenBank database with the accession number PP422198. The bacterial extract exhibited its effect against gram-positive bacteria, inhibiting Streptococcus mutans (12.6 ± 0.6 mm) and Staphylococcus aureus (10.6 ± 0.6 mm) compared to standard antibiotics. Conversely, compound 1 showed a considerable effect against phytopathogenic fungi such as Alternaria alternate (56.3 ± 10.6 mm) and Fusarium oxysporum (21.3 ± 1.5 mm) with a MIC value of 17.5 µg/mL. However, it was slightly active against Klebsiella pneumonia (11.0 ± 1.0 mm). Furthermore, compound 2 was the most active metabolite, having a significant antimicrobial efficacy against Rhizoctonia solani (63.6 ± 1.1 mm), Pseudomonas aeruginosa (16.7 ± 0.6 mm), and Alternaria alternate (20.3 ± 0.6 mm) with MIC value at 15 µg/mL. In addition, compound 2 exhibited the most potency against hepatocellular (HepG-2) and skin (A-431) carcinoma cell lines with IC50 values of 107.16 µg/mL and 111.36 µg/mL, respectively. CONCLUSION: Sphingomonas sanguinis DM, a rhizosphere bacterium of Datura metel, was studied for its phytochemical and biological characteristics, resulting in the identification of two compounds with moderate antimicrobial and cytotoxic activities.

Neuroprotective activity of Colocasia esculenta (L.) Schott leaves against monosodium glutamate-induced excitotoxicity in rats: phytochemical and molecular docking study.

Colocasia esculenta (L.) Schott is a food crop with long history of use in treatment of various disorders including neurological diseases. The methanolic leaves extract (ME) and its n-butanol fraction (n-BF) demonstrated significant in vivo neuroprotective activity in monosodium glutamate induced excitotoxicity in rats. Sixteen and fifteen polyphenolic compounds were identified in n-BF and ME, respectively, using HPLC. Phytochemical investigation of n-BF followed by 1D (1H and 13C NMR) spectroscopic analyses led to isolation and identification of daucosterol (1), thermopsoside (2) and chrysoeriol 7-O-ß-D-neohesperidoside (3) for the first time from genus Colocasia, in addition to orientin (4). LC/MS/MRM analysis of fraction V obtained from n-BF revealed identification of 13 polyphenolic compounds. Molecular docking of isolated compounds confirmed binding of all compounds at the target pocket with higher energy than crystallised ligand. The current study evaluated and confirmed the mechanistic aspects of neuroprotective activity of C. esculenta leaves for the first time.

Biobran-loaded core/shell nanofibrous scaffold: a promising wound dressing candidate.

This research examined the effectiveness of Biobran as a bioactive substance that could potentially improve wound healing. It also looked at how Biobran affects the properties of a nanofibrous scaffold made through coaxial electrospinning. This is the first study exploring the use of Biobran in this context and its interaction with nanofibrous scaffolds. The scaffolds were composed of poly(ε-caprolactone) (PCL) in the shell and various concentrations of Biobran blended with polyvinyl alcohol (PVA) in the core. The properties of the scaffolds were characterized by SEM, TEM, FTIR, XRD, TGA, DSC, stress-strain test, WCA, release test, MTT cytotoxicity assay, wound scratching assay, and the dye exclusion method using trypan blue. The scaffolds loaded with Biobran exhibited a more compact and smooth morphology compared with the scaffold without Biobran. The physical interaction and crystallinity of the polymers in the scaffolds were also affected by Biobran in a concentration-dependent manner. This positively influenced their tensile strength, elongation at break, thermal stability, and hydrophilicity. The porosity, water uptake capacity, and WVTR of the nanofibrous scaffolds are within the optimal ranges for wound healing. The release rate of Biobran, which revealed a biphasic release pattern, decreased with increasing Biobran concentration, resulting in controlled and sustained delivery of Biobran from the nanofiber scaffolds. The cell viability assays showed a dose-dependent effect of Biobran on WISH cells, which might be attributed to the positive effect of Biobran on the physicochemical properties of the nanofibrous scaffolds. These findings suggest that Biobran-loaded core/shell nanofiber scaffolds have a potential application in wound healing as an ideal multifunctional wound dressing.

Treatment of intramedullary spinal cord tumors: a modified Delphi technique of the North American Spine Society Section of Spine Oncology.

OBJECTIVE: Intramedullary spinal cord tumors (IMSCTs) are rare tumors with heterogeneous presentations and natural histories that complicate their management. Standardized guidelines are lacking on when to surgically intervene and the appropriate aggressiveness of resection, especially given the risk of new neurological deficits following resection of infiltrative tumors. Here, the authors present the results of a modified Delphi method using input from surgeons experienced with IMSCT removal to construct a framework for the operative management of IMSCTs based on the clinical, radiographic, and tumor-specific characteristics. METHODS: A modified Delphi technique was conducted using a group of 14 neurosurgeons experienced in IMSCT resection. Three rounds of written correspondence, surveys, and videoconferencing were carried out. Participants were queried about clinical and radiographic criteria used to determine operative candidacy and guide decision-making. Members then completed a final survey indicating their choice of observation or surgery, choice of resection strategy, and decision to perform duraplasty, in response to a set of patient- and tumor-specific characteristics. Consensus was defined as ≥ 80% agreement, while responses with 70%-79% agreement were defined as agreement. RESULTS: Thirty-six total characteristics were assessed. There was consensus favoring surgical intervention for patients with new-onset myelopathy (86% agreement), chronic myelopathy (86%), or progression from mild to disabling numbness (86%), but disagreement for patients with mild numbness or chronic paraplegia. Age was not a determinant of operative candidacy except among frail patients, who were deemed more suitable for observation (93%). Well-circumscribed (93%) or posteriorly located tumors reaching the surface (86%) were consensus surgical lesions, and participants agreed that the presence of syringomyelia (71%) and peritumoral T2 signal change (79%) were favorable indications for surgery. There was consensus that complete loss of transcranial motor evoked potentials with a 50% decrease in the D-wave amplitude should halt further resection (93%). Preoperative symptoms seldom influenced choice of resection strategy, while a distinct cleavage plane (100%) or visible tumor-cord margins (100%) strongly favored gross-total resection. CONCLUSIONS: The authors present a modified Delphi technique highlighting areas of consensus and agreement regarding surgical management of IMSCTs. Although not intended as a substitute for individual clinical decision-making, the results can help guide care of these patients. Additionally, areas of controversy meriting further investigation are highlighted.

Irrigation endoscopic discectomy: a novel percutaneous approach for lumbar disc prolapse.

PURPOSE: The purpose of this study is to present a new endoscopic procedure, aiming to achieve the success rate equivalent to microsurgical discectomy, while addressing the drawbacks and limitations of other percutaneous techniques. METHODS: A series of 43 patients with uncontained lumbar disc herniation underwent surgery with irrigation endoscopic discectomy (IED). The endoscope and instruments are placed directly over the surface of the lamina through two posterior skin portals 5 mm each without any muscle retraction or dilatation. Pump irrigation is used for the opening of a potential working space. The rest of the procedure is performed endoscopically like the standard microsurgical discectomy. RESULTS: Outcome according to modified Macnab criteria was excellent in 78%, good in 17%, and poor in 5% of patients. VAS for leg pain dropped from 78 preoperatively to 7, and the Oswestry Low-Back Pain Disability Questionnaire dropped from 76 to 19. The mean time for postoperative ambulation was 4 h, hospital stay was 8 h, and for return to work was 7 days. CONCLUSIONS: Preliminary clinical experience with IED shows it to be as effective as microsurgical discectomy, and in comparison to other percutaneous procedures addressing noncontained herniations, a reduction in the cost, technical difficulty and surgical invasiveness has been demonstrated.

Post-myelography paraplegia in a woman with thoracic stenosis.

CONTEXT: Myelography is a commonly performed diagnostic test used to assess spine pathology. Complications are unusual and usually self-limited. We report a rare case of transient paraplegia following myelography in a woman with thoracic stenosis. FINDINGS: A 51-year-old woman, 20 months status post-thoracic laminectomy, presented with progressive lower extremity weakness. The patient underwent myelography and post-myelography CT, and became paraplegic after the lumbar injection. Intravenous steroids were administered and a lumbar puncture was performed. The patient's neurologic function returned to baseline over the next 96 hours. CONCLUSION AND CLINICAL RELEVANCE: Myelography is generally a safe procedure, but on rare occasions serious complications can arise. Therapeutic maneuvers may be helpful in reversing neurologic deficit.

One-pot facile synthesis of hexagonal Bi2Te3 nanosheets and its novel nanocomposites: Characterization, anticancer, antibacterial, and antioxidant activities.

Bismuth Telluride (Bi2Te3) layered structure results in extraordinary features in diagnostic and therapeutic applications. However, Bi2Te3 synthesis with reliable stability and biocompatibility in biological systems was the major challenge that limited its biological application. Herein, reduced graphene oxide (RGO) or graphitic carbon nitride (CN) nanosheets were incorporated into Bi2Te3 matrix to improve exfoliation. Bi2Te3 nanoparticles (NPs) and its novel nanocomposites (NCs): CN@Bi2Te3 and CN-RGO@Bi2Te3 were solvothermally synthesized, physiochemically characterized and assessed for their anticancer, antioxidant, and antibacterial activities. X-ray diffraction depicted Bi2Te3 rhombohedral lattice structure. Fourier-transform infrared and Raman spectra confirmed NC formation. Scanning and transmission electron microscopy revealed 13 nm thickness and 400-600 nm diameter of hexagonal, binary, and ternary nanosheets of Bi2Te3-NPs/NCs. Energy dispersive X-ray Spectroscopy revealed the presence of Bi, Te, and carbon atoms in the tested NPs with negatively charged surfaces as depicted by zeta sizer. CN-RGO@Bi2Te3-NC displayed the smallest nanodiameter (359.7 nm) with the highest Brunauer-Emmett-Teller surface area and antiproliferative activity against MCF-7, HepG2 and Caco-2. Bi2Te3-NPs had the greatest scavenging activity (96.13 ± 0.4%) compared to the NCs. The NPs inhibitory activity was greater against Gram-negative bacteria than that of Gram-positive bacteria. Integration of RGO and CN with Bi2Te3-NPs enhanced their physicochemical properties and therapeutic activities giving rise to their promising capacity for future biomedical applications.