Cellulose-Conjugated Copper-Oxide Nanoparticles for the Treatment of Ethanol-Induced Gastric Ulcers in Wistar Rats.

Gastric ulcer (GU) is the most common and chronic inflammatory condition mediated by multiple immune cells like neutrophils, macrophages, and lymphocytes with multiple pro-inflammatory cytokine interleukins such as IL-8, IL-10, IL-ß, and interferon-γ (IFN-γ). Copper (Cu) is one of the essential micronutrients mainly found in the liver and brain. It plays a major role in metabolism, enzyme conversion, free radical scavenging, trafficking agents, and many others. Due to its various roles in the biological system, it can also be used as a therapeutic agent in many diseases like colon cancer, bone fracture healing, angiogenesis, as an antibacterial, wound-healing and radiotherapeutic agents. In this study, we used thiol-functionalized cellulose-conjugated copper-oxide nanoparticles (CuI/IIO NPs) synthesized under environmentally friendly conditions. We have evaluated the effects of cellulose-conjugated CuI/IIO NPs against ethanol-induced gastric ulcer in Wistar rats. The cellulose-conjugated CuI/IIO NPs were evaluated against different physical, histochemical, and inflammatory parameters. The NPs promoted mucosal healing by ameliorating ulcerative damage, restoring the histoarchitecture of gastric mucosa, and inhibiting pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß), and other inflammatory biomarkers such as myeloperoxidase (MPO) activity and nitric oxide (NO) levels. The current study's findings suggest that cellulose-conjugated CuI/IIO NPs exerted antiulcer effects on the preclinical rat model and have promising potential as a novel therapeutic agent for the treatment of gastric ulcers.

Thiol-Functionalized Cellulose-Grafted Copper Oxide Nanoparticles for the Therapy of Experimental Colitis in Swiss Albino Mice.

Ulcerative colitis (UC) is a chronic inflammatory disease, which deleteriously affects the lower end of the gastrointestinal tract, i.e., the colon and the rectum. UC affects colonic inflammatory homeostasis and disrupts intestinal barrier functions. Intestinal tissue damage activates the immune system and collectively worsens the disease condition via the production of various cytokines. Ongoing therapeutics of UC have marked limitations like rapid clearance, extensive first-pass metabolism, poor drug absorption, very low solubility, bioavailability, etc. Because of these restrictions, the management of UC demands a rational approach that selectively delivers the drug at the site of action to overcome the therapeutic limiting factors. Metallic nanoparticles (NPs) have good therapeutic efficacy against colitis, but their uses are limited due to adverse effects on the biological system. In this study, we have used biocompatible thiol-functionalized cellulose-grafted copper oxide nanoparticles (C-CuI/IIO NPs) to treat UC. The metal NPs alleviated the colitis condition as evidenced by the colon length and observed physical parameters. Analysis of histopathology demonstrated the recovery of the colon architecture damaged by dextran sulfate sodium-induced colitis. Treatment with C-CuI/IIO NPs reduced the disintegration of goblet cells and the retainment of sulfomucin. Significant downregulation of inflammatory markers like MPO activity, as well as levels of nitrite and TNF-α, was found following C-CuI/IIO NP treatment. The observations from the study suggested that intrarectal treatment of colitis with cellulose-based C-CuI/IIO NPs successfully combated the intestinal inflammatory condition.

A systematic study to unravel the potential of using polysaccharides based organic-nanoparticles versus hybrid-nanoparticles for pesticide delivery.

To daze conventional pesticide release limitations, nanotechnology-mediated pesticide delivery using natural polymers has been actively investigated. However, the lack of information on what are the beneficial/non-beneficial aspects of using hybrid- and organic-nanoparticles (NP) and among the polysaccharides which are better suited concerning pesticide loading efficiency (PLE wt%), entrapment efficiency, and sustained pesticide release (SPR %) has prompted us to investigate this study. In this report, we systematically investigated a series of polysaccharides such as starch (S), cellulose (C), aminocellulose (AC), and sodium carboxymethylcellulose (NaCMC) coated on magnetite NP (MNP, Fe3O4) and complete organic nanocarrier systems (starch and cellulose) that have no MNP part were compared for the PLE wt% and SPR % efficiencies for chlorpyrifos (ChP) insecticide. Overall, all nanocarriers (NCs) have shown good to excellent PLE wt% due to the smaller-sized NP obtained through optimal conditions. However, among the hybrid polysaccharides studied, starch MNP has shown a maximum PLE of 111 wt% in comparison with other polysaccharides (80-94 wt%) coated hybrid-NCs as well as with organic-NCs (81-87 wt%). The use of inorganic support does improve the PLE wt% markedly for starch but not for cellulose derivatives. Similarly, the SPR results of S-NP showed a remarkably better sustained release profile for ChP of 88% in 14 d. In contrast, other unfunctionalized and functionalized celluloses exhibited poor release profiles of 60%-20% for the same period. This study may help the researchers choose the right system for designing and achieving enhanced pesticide efficiency.

Synergistic Effects of Carbon Dots and Palladium Nanoparticles Enhance the Sonocatalytic Performance for Rhodamine B Degradation in the Absence of Light.

Carbon dot (CD) and palladium nanoparticle (Pd NP) composites are semiconducting materials having tremendous applications in catalysis with suitable band gaps. However, their combination with a suitable polymer matrix in sonophotocatalysis has not been explored. Herein, we have synthesized and characterized a new nanohybrid catalyst from a polyamide cross-linked CD-polymer and subsequent deposition of Pd NPs. A sonocatalytic activity of 99% rhodamine B dye degradation was achieved in mere 5 min in the dark. A model catalyst replacing CDs with benzene and other control studies revealed that the synergistic effects of CDs and Pd NPs enhance the sonocatalytic activity of the nanohybrid catalyst. Interestingly, visible light did not influence the activity significantly. Mechanistic investigations suggest that generation of reactive oxygen species on the surface of the CD-polymer initiated by ultrasound, which is further facilitated by Pd NPs, is the key for remarkable catalytic activity (a rate constant of 0.99 min-1). Recyclable heterogeneous catalysts under ambient conditions are promising for exploring sono-assisted dark catalysis for several avenues.

Tuning of cross-Glaser products mediated by substrate-catalyst polymeric backbone interactions.

Tuning of cross-Glaser products using different polymeric backbones supported by copper oxide nano-catalysts has been demonstrated by tweaking the substrate-catalyst interactions under greener conditions. Further, highly reactive magnetically separable and recyclable catalyst with scalability is demonstrated.

Designing of Push-Pull Chromophores with Tunable Electronic and Luminescent Properties Using Urea as the Electron Donor.

Urea-functionalized 4-ethynylbenzenes undergo facile formal [2 + 2] cycloaddition followed by retroelectrocyclization upon reaction with tetracyanoethylene, yielding 1,1,4,4-tetracyanobuta-1,3-dienes-based push-pull chromophores. Unlike the N,N'-dialkylamino group, urea functionalization provides easy access to further functionalization on these chromophores. The resulting chromophores exhibit unexpected white light emissions apart from various inherent properties like intramolecular charge-transfer band and redox behavior.

Osteoactivin, an anabolic factor that regulates osteoblast differentiation and function.

Osteoactivin (OA) is a novel glycoprotein that is highly expressed during osteoblast differentiation. Using Western blot analysis, our data show that OA protein has two isoforms, one is transmembranous and the other is secreted into the conditioned medium of primary osteoblasts cultures. Fractionation of osteoblast cell compartments showed that the mature, glycosylated OA isoform of 115 kDa is found in the membranous fraction. Both OA isoforms (secreted and transmembrane) are found in the cytoplasmic fraction of osteoblasts. Overexpression of EGFP-tagged OA in osteoblasts showed that OA protein accumulates into vesicles for transportation to the cell membrane. We examined OA protein production in primary osteoblast cultures and found that OA is maximally expressed during the third week of culture (last stage of osteoblast differentiation). Glycosylation studies showed that OA isoform of 115 kDa is highly glycosylated. We also showed that retinoic acid (RA) stimulates the mannosylation of OA protein. In contrast, tunicamycin (TM) strongly inhibited N-glycans incorporation into OA protein. The functional role of the secreted OA isoform was revealed when cultures treated with anti-OA antibody, showed decreased osteoblast differentiation compared to untreated control cultures. Gain-of-function in osteoblasts using the pBABE viral system showed that OA overexpression in osteoblast stimulated their differentiation and function. The availability of a naturally occurring mutant mouse with a truncated OA protein provided further evidence that OA is an important factor for terminal osteoblast differentiation and mineralization. Using bone marrow mesenchymal cells derived from OA mutant and wild-type mice and testing their ability to differentiate into osteoblasts showed that differentiation of OA mutant osteoblasts was significantly reduced compared to wild-type osteoblasts. Collectively, our data suggest that OA acts as a positive regulator of osteoblastogenesis.

Expression and function of periostin-isoforms in bone.

Periostin was originally identified in MC3T3-E1 osteoblast-like cells. We have identified an isoform of periostin referred to as periostin-like-factor (PLF). It is homologous to other proteins such as fasciclin I (fas I), MPB70, betaIG-H3, and Algal-CAMs. All of these proteins are implicated in regulating cell adhesion. PLF and the other isoforms of periostin differ in their C-terminal sequences. PLF and periostin differ in two specific regions, between 673 and 699 amino acids (aa) and 785-812 aa. Periostin isoforms are expressed in vivo and in vitro during the stages of osteoblast differentiation and maturation. Their mRNAs are present in pre-osteoblast cells as detected by in situ hybridization, and the proteins are between 86 and 93 kD in size as determined by Western blot analysis. Antisense oligonucleotides and antibodies directed against the isoforms of periostin were used to block the activity of these proteins. In both cases, the levels of osteoblast-specific-differentiation markers were markedly reduced suggesting a role for these proteins in osteoblast differentiation.

Expression of connective tissue growth factor in bone: its role in osteoblast proliferation and differentiation in vitro and bone formation in vivo.

Connective tissue growth factor (CTGF) is a secreted, extracellular matrix-associated signaling protein that regulates diverse cellular functions. In vivo, CTGF is expressed in many tissues with highest levels in the kidney and brain. The purpose of this study was twofold; first, to localize CTGF in normal bone in vivo during growth and repair, and second, to examine CTGF expression and function in primary osteoblast cultures in vitro and test its effect on bone formation in vivo. Northern and Western blot analyses confirmed that CTGF is expressed in normal long bones during the period of growth or modeling. In situ hybridization and immunohistochemical analysis demonstrated intense staining for CTGF mRNA and protein in osteoblasts lining metaphyseal trabeculae. Examination of CTGF expression in the fracture callus demonstrated that it was primarily localized in osteoblasts lining active, osteogenic surfaces. In primary osteoblast cultures, CTGF mRNA levels demonstrated a bimodal pattern of expression, being high during the peak of the proliferative period, abating as the cells became confluent, and increasing to peak levels and remaining high during mineralization. This pattern suggests that CTGF may play a role in osteoblast proliferation and differentiation as previously demonstrated for fibroblasts and chondrocytes. Treatment of primary osteoblast cultures with anti-CTGF neutralizing antibody caused a dose-dependent inhibition of nodule formation and mineralization. Treatment of primary osteoblast cultures with recombinant CTGF (rCTGF) caused an increase in cell proliferation, alkaline phosphatase activity, and calcium deposition, thereby establishing a functional connection between CTGF and osteoblast differentiation. In vivo delivery of rCTGF into the femoral marrow cavity induced osteogenesis that was associated with increased angiogenesis. This study clearly shows that CTGF is important for osteoblast development and function both in vitro and in vivo.