Facile synthesis of bromelain copper nanoparticles to improve the primordial therapeutic potential of copper against acute myocardial infarction in diabetic rats.

Our current investigation comprises the synthesis and pharmacological impact of bromelain copper nanoparticles (BrCuNP) against diabetes mellitus (DM) and associated ischemia/reperfusion (I/R) - induced myocardial infarction. Bromelain is a proteolytic enzyme obtained from Ananas comosus L. Merr., which has blood platelet aggregation inhibiting and arterial thrombolytic potential. Moreover, copper is well-known to facilitate glucose metabolism and strengthen cardiac muscle and antioxidant activity; although, chronic or long-term exposure to high doses of copper may lead to copperiedus. To restrict these potential hazards, we synthesized herbal nano-formulation which convincingly indicated the improved primordial therapeutic potential of copper by reformulating the treatment carrier with bromelain, resulting in facile synthesis of BrCuNP. DM was induced by administration of double cycle repetitive dose of low dose streptozotocin (20 mg/kg, i.p.) in high-fat diet- fed animals. DM and associated myocardial I/R injury were estimated by increased serum levels of total cholesterol, low-density lipoprotein, very low-density lipoprotein, lactate dehydrogenase, creatine kinase myocardial band, cardiac troponin, thiobarbituric acid reactive substances, tumor necrosis factor α, interleukin 6, and reduced serum level of high-density lipoprotein and nitrite/nitrate concentration. However, treatment with BrCuNP ameliorates various serum biomarkers by approving cardioprotective potential against DM- and I/R-associated injury. Furthermore, upturn of histopathological changes were observed in cardiac tissue of BrCuNP-treated rats in comparison to disease models.

Exercise preconditioning and low dose copper nanoparticles exhibits cardioprotection through targeting GSK-3ß phosphorylation in ischemia/reperfusion induced myocardial infarction.

BACKGROUND: Drinking water from copper vessels and aerobic exercise have been the known facts for cardioprotection. Our previous report explored the significant cardioprotective potential of copper and exercise training by increasing phosphorylation of GSK-3ß and anti-oxidant potential. OBJECTIVE: Present study focuses the therapeutic potential of CuNP and exercise training through their molecular interaction with GSK-3ß, inflammatory cytokinin, oxidative stress and necrosis. METHODS: The Myocardial damage was assessed by estimating the serum nitrite/nitrate concentration, increased CKMB, LDH, cTnI level, oxidative stress, inflammatory cytokinin and structural abnormalities in I/R insulted rats. Expression of Akt/pAkt and GSK-3ß/pGSK-3ß was measured by western blotting. RESULT: Treatment with CuNP (1 mg/kg/day, p.o., 4 weeks) and exercise training (swimming, 90 min/4 weeks) either alone or in combination markedly reduced I/R induced myocardial damage by attenuating biochemical and structural alteration. A significant reduction in oxidative stress and inflammatory mediators were observed in CuNP and exercise training treatment against I/R insulted rats. Moreover, improved serum NO bioavailability was observed in CuNP and exercise treated rats. Wortmannin associated blockage of cardioprotection induced by CuNP and exercise training and up-regulation of pAkt and pGSK-3ß in I/R insulted heart confirmed the GSK-3ß phosphorylation potential of CuNP and exercise training and -associated cardioprotection. CONCLUSION: Treatment with CuNP and exercise training either alone or in combination favourably phosphorylate GSK-3ß kinase pathways and further diminish oxidative stress, inflammatory cytokines, apoptosis and increase serum bioavailability of NO in the I/R insulted rats which tends to protect myocardial damage.

Adhesivity-tuned bioactive gelatin/gellan hybrid gels drive efficient wound healing.

Gelatin-based hydrogels have been widely used for wound healing applications. However, increase in ligand density and reduction in pore size with increasing gelatin concentration may delay wound healing by limiting cell infiltration. In this study, we address this shortcoming by combining gelatin with gellan-which is super hydrophilic and non-adhesive to cells. We show that UV crosslinked hybrid gels composed of methacrylated gelatin (GelMA) and methacrylated gellan gum (mGG), possess considerably larger pores and improved mechanical properties compared to GelMA gels. Reduced spreading and reduced formation of focal adhesions on hybrid gels combined with lower contractility and faster detachment upon trypsin-induced de-adhesion suggests that hybrid gels are less adhesive than GelMA gels. Gradual release of fibroblast growth factor (FGF) and silver nanoparticles (AgNPs) incorporated in hybrid gels not only boosts cell migration, but also confers anti-bacterial activity against gram-positive and gram-negative bacteria at concentrations nontoxic to cells. Full thickness wound healing in Wistar rats revealed increased granulation tissue formation in hybrid gels, fastest epithelialization and highest collagen deposition in rats treated with FGF entrapped hybrid gels. Together, our results demonstrate how adhesive tuning and incorporation of bioactive factors can be synergistically combined for achieving complete wound healing.

Mechanical properties of aerospace epoxy composites reinforced with 2D nano-fillers: current status and road to industrialization.

High-performance epoxy composites find application in the aerospace industry. Although epoxy is a high-performance polymer, its fracture toughness is compromised due to its highly cross-linked nature. Nanomaterials such as carbon nanotubes (CNTs), graphene derivatives, and inorganic 2-dimensional (2D) nanomaterials are being explored to improve epoxy composites' mechanical properties. Graphene is one of the most popular 2D nano-reinforcing agents for epoxy composites. Following graphene discovery, the research community's attention was brought to various other few-atom thick 2D nanomaterials. Hence, apart from graphene, inorganic nanosheets such as transition metal dichalcogenides (TMDs), hexagonal boron nitride (hBN), etc., are also being studied as modifiers for enhancing the mechanical performance of epoxy composites. Graphene, TMDs and hBN are known to possess a high aspect ratio, high specific surface area and inherently high mechanical strength and stiffness, contributing to a stronger and tougher composite. Despite that, the challenges associated with these nanomaterials, such as dispersion issues, lack of standardization, underlying health hazards, etc., have hampered their commercialization. It has been long past a decade since the discovery of graphene, yet there are concerns regarding the lab to industry scale-up, and health and environmental hazards associated with nanomaterials for the fabrication of aerospace composites. This review offers a comprehensive literature survey and a perspective into the possible ways of bridging the gaps between the laboratory research and industrialization of 2D nanosheet-filled epoxy composites.

Improving Fracture Toughness of Tetrafunctional Epoxy with Functionalized 2D Molybdenum Disulfide Nanosheets.

In this work, improved fracture toughness of tetra-functional epoxy polymer was obtained using two-dimensional (2H polytype) molybdenum disulfide (MoS2) nano-platelets as a filler. Simultaneous in-situ exfoliation and functionalization of MoS2 were achieved in the presence of cetyltrimethylammonium bromide (CTAB) via sonication. The aim was to improve the dispersion of MoS2 nanoplatelets in epoxy and enhance the interfacial interaction between nanoplatelets and epoxy matrix. Epoxy nanocomposites with CTAB functionalized MoS2 (f-MoS2) nanoplatelets, ranging in content from 0.1 wt% up to 1 wt%, were fabricated. Modified MoS2 improved the fracture properties (81%) of tetrafunctional epoxy nanocomposites. The flexural strength and compressive strength improved by 64% and 47%, respectively, with 0.25 wt% loading of f-MoS2 nanoplatelets compared to neat epoxy. The addition of f-MoS2 nanoplatelets enhanced the thermomechanical properties of epoxy. This work demonstrated the potential of organically modified MoS2 nanoplatelets for improving the fracture and thermal behavior of tetrafunctional epoxy nanocomposites.

Temporal dynamics of pre and post myocardial infarcted tissue with concomitant preconditioning of aerobic exercise in chronic diabetic rats.

The different ailments of heart including myocardial infarction (MI) and ischemic heart diseases are the foremost trigger of high mortality across the world which is instigated by sedentary life style, chronic hyperglycaemia and atherosclerosis. Albeit strenuous exercise itself induces temporary hypoxia which causes myocardial damage and this vitiosus circulus is poorly understood and has been assumed difficult to break. Present investigation targets temporal dynamics of aerobic exercise treatment induced preconditioning against diabetes associated pre- and post- myocardial injury. The persisting high blood sugar level leads to several biochemical alterations at pre- and post-MI phase. Here, we present the assessment of temporal expression of cardiac biomarkers (CKMB, LDH, cTnI and serum nitrite/nitrate), oxidative stress (myocardial TBARS and reduced NBT), inflammatory cytokines (IL-6, TNF-α and IL-10), renal biomarkers (BUN, serum creatinine and microproteinuria) and structural alterations of cardio-renal tissue. Aerobic exercise preconditioning significantly downregulate the pathological events or biomarkers and upsurge the physiological biomarkers at both pre- and post-MI phase. The attenuation or returning of pathological makers to lowest level at different time points endorses the therapeutic management of aerobic exercise against diabetic MI. Furthermore, the temporal expression of various cardio-renal biomarkers pattern elucidates that aerobic exercise preconditioning boost the strength and consolidate the cardiac muscles to work under stress. Despite the presence of traditional knowledge about health benefits of aerobic exercise, it is yet to be brought into the clinical arena. In spite of few impending challenges subjected to additional investigations, aerobic exercise preconditioning shows a high degree of promise.

Insulin analogs: Glimpse on contemporary facts and future prospective.

Insulin remains a predominant life-saving medication for type 1 and type 2 Diabetes Mellites. Natural insulin secretion limits the fluctuation of the narrow and high surge of blood glucose levels. However, imitating the same by external insulin remains a challenge as a variety of insulin analogs (rapid acting, short acting, intermediate acting and long-acting) have different pharmacokinetic (PK) and pharmacodynamic (PD) properties. Inconsistent reduction in overall hyperglycemia level and nocturnal hypoglycemia due to variable absorption time and time action profile predominantly highlights the need of revisiting the PK/PD of insulin analogs as single analog is not yet sufficed to replace internal insulin exogenously. Combination therapy with basal and prandial insulins or intensification of hypoglycemic therapy with premixed insulins are of prime importance in managing diabetes effectively, imitating the natural insulin secretion. Therefore, the knowledge of PK/PD properties might help a practitioner to design, implement and manage insulin replacement therapy effectively and averting adverse events. Present study reports the comparative analysis of PK/PD profile of various insulin analogs based on the concurrent information about clinical aspects. Moreover, study interlinks the major concerns of therapeutic efficacy of insulin analogs with their respective onset of action and duration of effectiveness and reported adverse drug reaction which explore the scope of improvement.

Noncovalently Functionalized Tungsten Disulfide Nanosheets for Enhanced Mechanical and Thermal Properties of Epoxy Nanocomposites.

In the present study, noncovalently functionalized tungsten disulfide (WS2) nanosheets were used as a toughening agent for epoxy nanocomposites. WS2 was modified with branched polyethyleneimine (PEI) to increase the degree of interaction of nanosheets with the epoxy matrix and prevent restacking and agglomeration of the sheets in the epoxy matrix. The functionalization of WS2 sheets was confirmed through Fourier transform infrared spectroscopy and thermogravimetric analysis. The exfoliation of the bulk WS2 was confirmed through X-ray diffraction and various microscopic techniques. Epoxy nanocomposites containing up to 1 wt % of WS2-PEI nanosheets were fabricated. They showed a remarkable improvement in fracture toughness (KIC). KIC increased from 0.94 to 1.72 MPa m-1/2 for WS2-PEI nanosheet loadings as low as 0.25 wt %. Compressive and flexural properties also showed a significant improvement as incorporation of 0.25 wt % of WS2-PEI nanosheets resulted in 43 and 65% increase in the compressive and flexural strengths of epoxy nanocomposites, respectively, compared with neat epoxy. Thermal stability and thermomechanical properties of the WS2-PEI-modified epoxy also showed a significant improvement. The simultaneous improvement in the mechanical and thermal properties could be attributed to the good dispersion of WS2-PEI nanosheets in the matrix, intrinsic high strength and thermal properties of the nanosheets, and improved interaction of the WS2 nanosheets with the epoxy matrix owing to the presence of PEI molecules on the surface of the WS2 nanosheets.