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Frisk Muir posted an update 5 months ago
Bacterial canker disease caused by Pseudomonas syringae pv. actinidiae (Psa) biovar 3 involved all global interest since 2008. We have found that in Psa3 genome, similarly to other P. syringae, there are three putative genes, lscα, lscβ and lscγ, coding for levansucrases. These enzymes, breaking the sucrose moiety and releasing glucose can synthetize the fructose polymer levan, a hexopolysaccharide that is well known to be part of the survival strategies of many different bacteria. Considering lscα non-coding because of a premature stop codon, in the present work we cloned and expressed the two putatively functional levansucrases of Psa3, lscβ and lscγ, in E. coli and characterized their biochemical properties such as optimum of pH, temperature and ionic strength. Interestingly, we found completely different behaviour for both sucrose splitting activity and levan synthesis between the two proteins; lscγ polymerizes levan quickly at pH 5.0 while lscβ has great sucrose hydrolysis activity at pH 7.0. Moreover, we demonstrated that at least in vitro conditions, they are differentially expressed suggesting two distinct roles in the physiology of the bacterium.An eco-friendly superabsorbent composites of xanthan gum-g-polyacrylic acid/semi-coke (XG-g-PAA/SC) were fabricated via grafting of polyacrylic acid onto the XG in the presence of SC. The obtained products were characterized in combination with Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The result indicated that the SC interacted with the polymeric network by hydrogen bond or electrostatic interaction. The swelling ratio of the best sample XG-g-PAA/SC (15 wt%) in distilled water and 0.9 wt% NaCl solution was 410.8 and 61.5 g/g by optimizing the polymerization conditions. In addition, compared with the blank sample (only containing soil), it can be found that adding a certain amount of XG-g-PAA/SC can significantly improve the soil water retention efficiency, which can be further proved by the results of plant pot experiment. Based on the above excellent swelling capacity, water holding capacity and plant growth promoting performance, it can be inferred that the XG-g-PAA/SC is expected to become a water retaining agent or soil regulator for plant growth.Chitosan/zeolite-A nanocomposite (CH/ZA) was synthesized as a potential carrier for levofloxacin (LVOX) of enhanced technical properties. The CH/ZA composite displayed enhanced loading capacity (425 mg/g) as compared to chitosan (188.8 mg/g) and zeolite-A (234.6 mg/g). The loading behavior follows Pseudo-Second-order and Langmuir as kinetic and isotherm models. The equilibrium studies, Gaussian energy (8.15 KJ/mol), and thermodynamic parameters demonstrate homogenous and monolayer loading by complex chemical and physical reactions that are of spontaneous and exothermic nature. The CH/ZA composite is of slow and continuous release profile (200h) with 94.3% as the maximum release percentage. The release reactions are of non-Fickian behavior involving both diffusion and erosion mechanisms. The loading of LVOX into CH/ZA induced its anti-inflammatory effect against the cytokine production (IL-6 and IL-8) within the human bronchial epithelia cells (NL20). The cytotoxicity studies on the normal cells demonstrated a high safety value for the composite.Gold nanoparticles/polyaniline boronic acid/sodium alginate aqueous nanocomposite ((PABA-SAL)@AuNPs) was fabricated. Aniline boronic acid (ABA) served as reductant of gold salt, all within the SAL solution. While ABA reduced gold salt to its nanoparticles, the ABA monomer was also oxidized to its conducting polymeric form (PABA). The presence of PABA in the reaction mixture exerted solubility and stability challenge, thus SAL was used as stabilizer and solubilizer for PABA. The numerous cis-diol groups of SAL could bind to boronic acid groups of PABA to furnish PABA-SAL repeating polymer structure for AuNPs anchoring. Sparkling ruby red (PABA-SAL)@AuNPs have absorption peaks at 529 and 718 nm. Average particle sizes of nanocomposite were within 15-20 nm, with hydrodynamic diameter of 48.6 ± 0.9 nm, zeta potential of -32.5 ± 1.6 mV and conductivity value of 2015.3 ± 3.2 μS/cm. (PABA-SAL)@AuNPs possessed antibacterial activities against seafood associated bacterial isolates, with MIC and MBC ranging from 4 to 8 μg/mL. The moderate antioxidant capacity of (PABA-SAL)@AuNPs was observed, without any deleterious damages on human red blood cells. It also has good biocompatibility on Caco-2 and RAW 264.7, with cell viability not less than 70%. These results confirm the high prospect of (PABA-SAL)@AuNPs for possible biomedical applications.Inhibition of protein fibrillation process with nanomaterials is a promising strategy to combat neurodegenerative diseases. Copper-based nanomaterials have been seldom utilized in fibrillation inhibiting research due to Copper ions are generally considered as accelerators of fibrosis. Here, we proposed ultra-small Zn doped Cu2S (ZnCu2S) QDs as inhibitors of human insulin (HI) fibrosis. ThT, DLS, CD and TEM confirm that ZnCu2S QDs effectively inhibited insulin fibrosis in a dose-dependent manner with lag phase time extended (beyond 13-time by ZnCu2S QDs of 1 mg·mL-1), final fibril formation and the conversion from α-helix to β-sheet reduced. Additionally, thermodynamics analyzed results reveal that the HI fluorescence quenching process is static quenching dominated, and the ZnCu2S QDs inhibit HI fibrosis mainly through specific electrostatic interaction with oligomers. The positively charged amino acid residues of oligomers bind to the negatively charged ZnCu2S QDs, which prevents the self-assembly of the oligomers from growing into mature fibers to enhance the stability of the protein. Unlike free Copper ions, the as-prepared QDs show an excellent inhibition in HI fibrillation, breaking through the bottleneck of copper-based materials in inhibiting protein fibrosis and providing a potential strategy to inhibit protein fibrosis in-situ by biosynthesizing copper-based fibrosis inhibitors.Starch nanoparticles were prepared by citrate esterification and ultrasound treatment. With the increase of ultrasonic treatment time, the mean size and PDI of the particles decreased gradually, when the ultrasonic treatment time was 5 min, the prepared starch nanoparticles had a mean size and PDI of 352.8 nm and 0.292, respectively. X-ray diffraction (XRD) showed that the starch nanoparticles prepared by ultrasonic treatment for 5 min had an A-type crystalline structure and a crystallinity of 41.42%. The chitosan composite films were reinforced by esterified starch with different ultrasound treatment times, the results indicated that the addition of starch nanoparticles resulted in a significant increase in the mechanical properties of films. This study indicates that esterification and ultrasound treatment can be used to prepare starch nanoparticles with a higher crystallinity and higher efficiency, which will further promote the application of nanocomposite films in packaging applications.Congenital aniridia is a rare genetic eye disorder with total or partial absence of the iris from birth. In most cases the genetic origin of aniridia is a mutation in the PAX6 gene, leading to involvement of most eye structures. Hypoplasia of the fovea is usually present and is associated with reduced visual acuity and nystagmus. Aniridia-associated keratopathy, glaucoma, and cataract are serious and progressive complications that can further reduce visual function. Treatment of the ocular complications of aniridia is challenging and has a high risk of side effects. New approaches such as stem cell therapy may, however, offer better prognoses. We describe the various ocular manifestations of aniridia, with a special focus on conditions that commonly require treatment. Selleck Elimusertib We also review the growing literature reporting systemic manifestations of the disease.
Nucleotide leukin-rich polypeptide 3 (NLRP3) inflammasome is documented as a potent target for treating metabolic diseases and inflammatory disorders. Our recent work demonstrated that inhibition of NLRP3 inflammasome activation inhibits renal inflammation and fibrosis in diabetic nephropathy. This study was to investigate the effect of NLRP3 inflammasome on podocyte injury and the underlying mechanism in diabetic nephropathy.
In vivo, db/db mice were treated with MCC950, a NLRP3 inflammasome specific inhibitor. NLRP3 knockout (NKO) mice were induced to diabetes by intraperitoneal injections of streptozotocin (STZ). We assessed renal function, albuminuria, podocyte injury and glomerular lipid accumulation in diabetic mice. In vitro, apoptosis, cytoskeleton change, lipid accumulation, NF-κB p65 activation and reactive oxygen species (ROS) generation were evaluated in podocytes interfered with NLRP3 siRNA or MCC950 under high glucose (HG) conditions. In addition, the effect and mechanism of IL-1β on lipid ainflammasome protects against podocyte damage through suppression of lipid accumulation in diabetic nephropathy. IL-1β/ROS/NF-κB p65 mediates diabetes-associated lipid accumulation in podocytes. The suppression of NLRP3 inflammasome activation may be an effective therapeutic approach to diabetic nephropathy.
Inhibition of NLRP3 inflammasome protects against podocyte damage through suppression of lipid accumulation in diabetic nephropathy. IL-1β/ROS/NF-κB p65 mediates diabetes-associated lipid accumulation in podocytes. The suppression of NLRP3 inflammasome activation may be an effective therapeutic approach to diabetic nephropathy.Oxygen is a critical noncellular component of the bone marrow microenvironment that plays an important role in the development of hematopoietic cell lineages. In this study, we investigated the impact of low oxygen (hypoxia) on ex vivo myeloerythroid differentiation of human cord blood-derived CD34+ hematopoietic stem and progenitor cells. We characterized the culture conditions to demonstrate that low oxygen inhibits cell proliferation and causes a metabolic shift in the stem and progenitor populations. We found that hypoxia promotes erythroid differentiation by supporting the development of progenitor populations. Hypoxia also increases the megakaryoerythroid potential of the common myeloid progenitors and the erythroid potential of megakaryoerythroid progenitors and significantly accelerates maturation of erythroid cells. Specifically, we determined that hypoxia promotes the loss of CD71 and the appearance of the erythroid markers CD235a and CD239. Further, evaluation of erythroid populations revealed a hypoxia-induced increase in proerythroblasts and in enucleation of CD235a+ cells. These results reveal the extensive role of hypoxia at multiple steps during erythroid development. Overall, our work establishes a valuable model for further investigations into the relationship between erythroid progenitors and/or erythroblast populations and their hypoxic microenvironment.
The molecular control of inflammation and epidermal thickening in skin lesions of patients with atopic dermatitis (AD) is not known. Sequestosome 1/p62 is a multifunctional adapter protein implicated in the control of key regulators of cellular homeostasis, such as proinflammatory and mechanistic target of rapamycin signaling.
We sought to determine whether p62 plays a role in the cutaneous and systemic manifestations of an AD-like mouse model.
AD-like skin lesions were induced by deletion of JunB/AP-1, specifically in epidermal keratinocytes (JunB
). The contribution of p62 to pathological changes was determined by inactivation of p62 in JunB
p62
double knockout mice.
Expression of p62 was elevated in skin lesions of JunB
mice, resembling upregulation of p62 in AD and psoriasis. When p62 was inactivated, JunB
-associated defects in the differentiation of keratinocytes, epidermal thickening, skin infiltration by mast cells and neutrophils, and the development of macroscopic skin lesions were significantly reduced.