Elucidating the interplay of PPAR gamma inhibition and energy demand in adriamycin-induced cardiomyopathy: In Vitro and In Vivo perspective.

Adriamycin is an anticancer anthracycline drug that inhibits the progression of topoisomerase II activity and causes apoptosis. The effective clinical application of the drug is very much limited by its adverse drug reactions on various tissues. Most importantly, Adriamycin causes cardiomyopathy, one of the life-threatening complications of the drug. Altered expression of PPARγ in adipocytes inhibited the glucose and fatty acids uptake by down regulating GLUT4 and CD36 expression and causes cardiotoxicity. Therefore, the influence of Adriamycin in cardiac ailments was investigated in vivo and in vitro. Adriamycin treated rats showed altered ECG profile, arrhythmic heartbeat with the elevated levels of CRP and LDH. Dysregulated lipid profiles with elevated levels of cholesterol and triglycerides were also observed. Possibilities of cardiac problems due to cardiomyopathy were analyzed through histopathology. Adriamycin treated rats showed no signs for atheromatous plaque formation in aorta but disorganized cardiomyocytes with myofibrillar loss and inflammation in heart tissue, indicative of cardiomyopathy. Reduced levels of antioxidant enzymes confirmed the incidence of oxidative stress. Adriamycin treatment significantly reduced glucose and insulin levels, creating energy demand due to decreased glucose and insulin levels with increased fatty acid accumulation, ultimately resulting in oxidative stress mediated cardiomyopathy. Since PPARs play a vital role in regulating oxidative stress, the effect of Adriamycin on PPARγ was analyzed by western blot. Adriamycin downregulated PPARγ in a dose-dependent manner in H9C2 cells in vitro. Overall, our study suggests that Adriamycin alters glucose and lipid metabolism via PPARγ inhibition that leads to oxidative stress and cardiomyopathy that necessitates a different therapeutic approach.

Mollification of Doxorubicin (DOX)-Mediated Cardiotoxicity Using Conjugated Chitosan Nanoparticles with Supplementation of Propionic Acid.

Doxorubicin is an extensively prescribed antineoplastic agent. It is also known for adverse effects, among which cardiotoxicity tops the list. The possible mechanism underlying doxorubicin (DOX)-mediated cardiotoxicity has been investigated in this study. Further, to reduce the DOX-mediated cardiotoxicity, DOX was conjugated with Chitosan Nanoparticles (DCNPs) and supplemented with propionic acid. Initially, the drug loading efficacy and conjugation of DOX with chitosan was confirmed by UV-Visible Spectroscopy (UV) and Fourier Transform Infrared Spectroscopy (FTIR). The average sizes of the synthesized Chitosan Nanoparticles (CNPs) and DCNPs were measured by Dynamic Light Scattering (DLS) analysis as 187.9 ± 1.05 nm and 277.3 ± 8.15 nm, respectively, and the zeta potential values were recorded as 55.2 ± 0.7 mV and 51.9 ± 1.0 mV, respectively. The size and shape of CNPs and DCNPs were recorded using a High-Resolution Electron Microscopy (HRTEM). The particles measured <30 nm and 33-84 nm, respectively. The toxic effects of DCNPs and propionic acid were evaluated in rat model. The data from the electrocardiogram (ECG), cardiac biomarkers, Peroxisome proliferator-activated receptor gamma (PPARγ) and histological observations indicated evidence of DOX-mediated cardiotoxicity, whereas the administration of DCNPs, as well as Propionic Acid (PA), brought about a restoration to normalcy and offered protection in the context of DOX-induced cardiotoxicity.

Structural elucidation of estrus urinary lipocalin protein (EULP) and evaluating binding affinity with pheromones using molecular docking and fluorescence study.

Transportation of pheromones bound with carrier proteins belonging to lipocalin superfamily is known to prolong chemo-signal communication between individuals belonging to the same species. Members of lipocalin family (MLF) proteins have three structurally conserved motifs for delivery of hydrophobic molecules to the specific recognizer. However, computational analyses are critically required to validate and emphasize the sequence and structural annotation of MLF. This study focused to elucidate the evolution, structural documentation, stability and binding efficiency of estrus urinary lipocalin protein (EULP) with endogenous pheromones adopting in-silico and fluorescence study. The results revealed that: (i) EULP perhaps originated from fatty acid binding protein (FABP) revealed in evolutionary analysis; (ii) Dynamic simulation study shows that EULP is highly stable at below 0.45 Å of root mean square deviation (RMSD); (iii) Docking evaluation shows that EULP has higher binding energy with farnesol and 2-iso-butyl-3-methoxypyrazine (IBMP) than 2-naphthol; and (iv) Competitive binding and quenching assay revealed that purified EULP has good binding interaction with farnesol. Both, In-silico and experimental studies showed that EULP is an efficient binding partner to pheromones. The present study provides impetus to create a point mutation for increasing longevity of EULP to develop pheromone trap for rodent pest management.

Examining and elucidation of human weight cycle model adopting e-cell simulation system.

Cellular rhythms regulate various physiological functions in circadian oscillatory mechanisms. Weight cycling or 'yo-yo' dieting is an evitable process in human, because of subsequent loss and regain of body weight due to irregular diet. Human weight cycle (HWC) is the major factor for causing global epidemic diseases in human beings. Understanding the HWC process would provide potent additional knowledge to prevent obesity. However till date, there is no study dealing with examine the HWC model using virtual cell simulation based on system biological approach. Therefore, the present study was designed to develop a computational HWC model, which was simulated using E-cell system v3.0. The developed model has the cyclic feedback reactions of three significant variables (the consecutive cycles of weight loss in continuous food intake (Q) and regain of body weight (P) at highest threshold point of cognitive restraint (R)) which are obtained by mathematical modelling. The dynamic plot results supported that the PQR variables depicted sustained oscillation with reversible modification due to protein diet. By contrast, the virtual model simulation would provide extensive information on HWC, which might provide knowledge to develop HWC linked with obesity pathway. The presents study concludes that optimization of body weight is essential to prevent the obesity based diseases.

Laser receptive polyelectrolyte thin films doped with biosynthesized silver nanoparticles for antibacterial coatings and drug delivery applications.

We report a simple method to fabricate multifunctional polyelectrolyte thin films to load and deliver the therapeutic drugs. The multilayer thin films were assembled by the electrostatic adsorption of poly (allylamine hydrochloride) (PAH) and dextran sulfate (DS). The silver nanoparticles (Ag NPs) biosynthesized from novel Hybanthus enneaspermus leaf extract as the reducing agent were successfully incorporated into the film. The biosynthesized Ag NPs showed excellent antimicrobial activity against the range of enteropathogens, which could be significantly enhanced when used with commercial antibiotics. The assembled silver nano composite multilayer films showed rupture and deformation when they are exposed to laser. The Ag NPs act as an energy absorption center, locally heat up the film and rupture it under laser treatment. The antibacterial drug, moxifloxacin hydrochloride (MH) was successfully loaded into the multilayer films. The total amount of MH release observed was about 63% which increased to 85% when subjected to laser light exposure. Thus, the polyelectrolyte thin film reported in our study has significant potential in the field of remote activated drug delivery, antibacterial coatings and wound dressings.

Antimicrobial activity of Leucas aspera engineered silver nanoparticles against Aeromonas hydrophila in infected Catla catla.

This research describes green synthesis of silver nanoparticles (AgNPs) utilizing Leucas aspera. The synthesized nanoparticles were characterized by UV-visible spectroscopy (UV-vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infra-red spectroscopy (FTIR) and inductively coupled plasmon optical emission spectroscopy (ICP-OES). UV-vis analysis proved the wavelength of the sample to be 429 nm, resembling the surface resonance peak (SPR) specific for AgNPs. DLS analysis indicated particles with superior stability with an average diameter of 189.3 nm. TEM results showed that the particles were in the size range of 29-45 nm. FTIR prediction indicated the presence of possible polyphenol and protein encapsulates on the AgNPs. Antimicrobial activity of the AgNPs was tested against Aeromonas hydrophila. Catla catla, the model organism used for the experiment was divided into six groups with 15 animals in each group. In vivo analysis of biochemical parameters and histological architecture provided evidence for the antibacterial effect of AgNPs in the fish model.

Hepatocurative activity of biosynthesized silver nanoparticles fabricated using Andrographis paniculata.

The current investigation was aimed to determine the hepatocurative role of silver nanoparticles (AgNPs) synthesized rapidly using Andrographis paniculata. The nanoparticles fabricated at varying temperatures were characterized by UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), fourier transform infra-red spectroscopy (FTIR), energy dispersive X-ray (EDX) and inductively coupled plasma optical emission spectroscopy (ICP-OES) alongside zeta potential measurement. UV-vis spectroscopic readings indicated a prominent peak at 423 nm. TEM analysis indicated that the biosynthesized nanospheres were in the size range of 13-27 nm. EDX spectrum indicated strong signal for AgNPs with 90.1% purity. The total concentration of AgNps was 216.7 mg/L after synthesis as by ICP-OES. Zeta potential was -34.3 mV indicating stable AgNPs. In vitro radical scavenging assay proved strong antioxidant effect of the AgNPs compared to 5% aqueous leaf extract. CCl(4) was used to induce hepatic injury in mice model. The biosynthesized AgNPs at three different doses (25, 50, 100mg/kg BW of the animal) were used for treatment. Silymarin was used as a standard. Low dose (25mg/kg BW) was effective in revival of all biological parameters to near normal in all intoxicated groups indicating the curing effects on CCl(4) induced liver injury.

In vivo antitumor activity of biosynthesized silver nanoparticles using Ficus religiosa as a nanofactory in DAL induced mice model.

Ficus religiosa leaf extract was chosen as a reducing agent to fabricate silver nanoparticles (AgNPs) by a simple, cost-effective and eco-friendly process with the aim of treating Dalton's ascites lymphoma (DAL) in mice model. The formation of synthesized nanoparticles were characterized by UV-visible analysis (UV-vis), Fourier transform infra-red (FT-IR), transmission electron microscopy (TEM), X-ray diffraction (XRD) and zeta potential analyses. A peak at 431nm indicated the surface plasmon resonance of AgNPs. FTIR studies indicated polyphenols and proteins as possible encapsulates. TEM analysis showed particles size in the range of 5-35nm. Healthy Swiss Albino mice (30-35g) were intraperitoneally induced with DAL cells and treated with F. religiosa derived AgNPs at a dose of 50µg/ml. Blood and liver tissues were collected subsequent to dissection and subjected to hematological, biochemical and anticancer assays. Hematological and biochemical analyses revealed revival after treating with F. religiosa derived AgNPs. Antioxidant activity results further proved supportive evidence. The apoptosis inducing effect of AgNPs was observed through acridine orange staining (AO and EB) and DNA fragmentation assay. Anti- angiogenic activity was confirmed by observing vessel development. All these observations indicate that the AgNPs were effective in treatment of DAL.

Mangrove Streptomyces sp. BDUKAS10 as nanofactory for fabrication of bactericidal silver nanoparticles.

Biosynthesis has led to the development of various biomimetic approaches for the fabrication of nanoscale materials. The present study reveals a unique procedure for the biosynthesis of bactericidal silver nanoparticles (AgNPs) using a novel Streptomyces sp. BDUKAS10, an isolate of mangrove sediment. Aqueous silver nitrate (AgNO(3)) solution was treated with cell free supernatant (CFS) of the isolate to synthesize bactericidal silver nanoparticles. Initial characterization was performed by visual observation for color change to intense brown color. UV-visible spectrophotometry (UV-vis) for measuring surface plasmon resonance indicated a maximum absorption peak at 441 nm. Fourier Transform Infrared Spectroscopy (FTIR) analysis provides evidence for proteins as possible reducing, and capping agents. Energy dispersive X-ray (EDAX) spectroscopy analysis showed elemental silver as major signal. Transmission Electron Microscopy (TEM) study indicated spherical silver nanoparticles in the size range of 21-48 nm. Compared to the CFS, the biosynthesized AgNPs exemplified superior bactericidal efficacy towards the tested bacterial strains. Results from this study suggested that Streptomyces sp. BDUKAS10 can be advantageous for the synthesis of AgNPs by extracellular method in the view of sustainable and ecofriendly approach.

Comparative evaluation of antibacterial activity of silver nanoparticles synthesized using Rhizophora apiculata and glucose.

The focus of the study is to compare the antibacterial efficacy of silver nanoparticles (AgNPs) fabricated by exploiting biological (a mangrove plant, Rhizophora apiculata) and chemical means (Glucose). The synthesized nanoparticles were characterised using UV-visible absorption spectrophotometry (UV-vis), Fourier transform Infra-red Spectroscopy (FTIR) and Transmission electron microscopy (TEM). Biologically synthesized silver nanoparticles (BAgNPs) were observed at 423 nm with particle sizes of 19-42 nm. The chemically synthesized silver nanoparticles (CAgNPs) showed a maximum peak at 422 nm with particle sizes of 13-19 nm. An obvious superiority of the antibacterial potency of BAgNPs compared to the CAgNPs as denoted by the zone of inhibition (ZoI) was noted when the nanoparticles were treated against seven different Microbial Type Culture Collection (MTCC) strains. The current study therefore elucidates that the synthesized AgNPs were efficient against the bacterial strains tested.