Sex-related differences in delayed doxorubicin-induced cardiac dysfunction in C57BL/6 mice.

Cancer survivors may experience long-term cardiovascular complications due to chemotherapeutic drugs such as doxorubicin (DOX). The exact mechanism of delayed DOX-induced cardiotoxicity has not been fully elucidated. Sex is an important risk factor for DOX-induced cardiotoxicity. In the current study, we identified sex differences in delayed DOX-induced cardiotoxicity and determined the underlying molecular determinants of the observed sexual dimorphism. Five-week-old male and female mice were administered intraperitoneal injections of DOX (4 mg/kg/week) or saline for 6 weeks. Echocardiography was performed 5 weeks after the last dose of DOX to evaluate cardiac function. Thereafter, mice were sacrificed and gene expression of markers of apoptosis, senescence, and inflammation was measured by PCR in hearts and livers. Proteomic profiling of the heart from both sexes was conducted to determine differentially expressed proteins (DEPs). Only DOX-treated male, but not female, mice demonstrated cardiac dysfunction, cardiac atrophy, and upregulated cardiac expression of Nppb and Myh7. No sex-related differences were observed in DOX-induced expression of most apoptotic, senescence, and pro-inflammatory markers. However, the gene expression of Trp53 was significantly reduced in hearts of DOX-treated female mice only. The anti-inflammatory marker Il-10 was significantly reduced in hearts of DOX-treated male mice only, while the pro-inflammatory marker Il-1α was significantly reduced in livers of DOX-treated female mice only. Gene expression of Tnf-α was reduced in hearts of both DOX-treated male and female mice. Proteomic analysis identified several DEPs after DOX treatment in a sex-specific manner, including anti-inflammatory acute phase proteins. This is the first study to assess sex-specific proteomic changes in a mouse model of delayed DOX-induced cardiotoxicity. Our proteomic analysis identified several sexually dimorphic DEPs, many of which are associated with the anti-inflammatory marker Il-10.

Treatment of Escherichia coli contaminated water with different pulse-powered NTP configurations and analysis for post treatment efficacy.

A cost-effective and energy efficient method for water sterilization is a challenging demand in the present scenario where scarcity of pure water is rising. Non-Thermal Plasma (NTP) finds promising applications in environmental processes and has advantages over conventional water treatment methods. Escherichia coli contaminated water treatment using multiple pin plasma reactor and atmospheric pressure plasma jet reactor was undertaken in this work. High voltage pulsed power was used for generating non-thermal plasma in these reactors and various configurations were tested for treating the contaminated water. The most feasible configuration among these was identified from the treatment efficiency and survival rate plots of E. coli colonies. It was observed that with an exposure of 15 min NTP, 100 percent bacterial removal was achieved using plasma jet reactor configuration. The presence of bacteria after NTP-treated time was also checked and confirmed for complete removal of bacteria. An optimum time of 15 min plasma exposure for 100 ml was found to be effective for complete removal of microorganisms and the sterility was maintained up to 60 min after the treatment. Non-thermal plasma-based treatment of bacteria-contaminated water is found to be promising and could be considered for scale-up and analysis.

Bioinspired gelatin based sticky hydrogel for diverse surfaces in burn wound care.

Proper burn wound management considers patient's compliance and provides an environment to accelerate wound closure. Sticky hydrogels are conducive to wound management. They can act as a preventive infection patch with controlled drug delivery and diverse surface adherence. A hypothesis-driven investigation explores a bioinspired polydopamine property in a gelatin-based hydrogel (GbH) where polyvinyl alcohol and starch function as hydrogel backbone. The GbH displayed promising physical properties with O-H group rich surface. The GbH was sticky onto dry surfaces (glass, plastic and aluminium) and wet surfaces (pork and chicken). The GbH demonstrated mathematical kinetics for a transdermal formulation, and the in vitro and in vivo toxicity of the GbH on test models confirmed the models' healthy growth and biocompatibility. The quercetin-loaded GbH showed 45-50% wound contraction on day 4 for second-degree burn wounds in rat models that were equivalent to the silver sulfadiazine treatment group. The estimates for tensile strength, biochemicals, connective tissue markers and NF-κB were restored on day 21 in the GbH treated healed wounds to imitate the normal level of the skin. The bioinspired GbH promotes efficient wound healing of second-degree burn wounds in rat models, indicating its pre-clinical applicability.

Identification of Alzheimer associated differentially expressed gene through microarray data and transfer learning-based image analysis.

Major factors contribute to mental stress and enhance the progression of late-onset Alzheimer's disease (AD). The factors that lead to neurodegeneration, such as tau protein hyperphosphorylation and increased amyloid-beta production, can be mimicked in animal stress models. The present study identifies differentially expressed genes (DEGs) data and its corresponding predictive image analysis in rat models. The gene expression profile of GSE72062, GSE85162, GSE143951 and GSE85238 was downloaded from NCBI, GEO archive to analyse DEGs. Functional enrichment and pathway relationship networks, gene signal, protein interaction and micro-RNA interaction DEGs networks were constructed and investigated. The image analysis of histopathological slides of rat brain images corresponding to AD microarray-based DEGs profile was undertaken using the convolution neural networks (ConvNets) model. Enrichment of network in terms of GO concluded with 10 DEGs, namely ARHGAP32, GNA11, NR5A1, GNAT3, FOSL1, HELZ2, NMUR2, BDKRB1, RPL3L and RPL39L as potential gene targets to control neurodegeneration and progression of sporadic AD. The image analysis of AD microarray-based DEGs profile builds a successful predictive model of 89% and 61% training and test accuracy with a minimum of 2.480% loss using transfer learning, VGG16 model. Interestingly, the ARHGAP32 gene, a Rho GTPase activating class, was identified to have a functional relationship with two significant genes BCL2 and MMP9, that are well explored in AD. The current investigation upgrades the traditional pre-clinical AD research using microarray data analysis and ConvNets. The model successfully predicts DEG from histopathology slides of rat brain samples, paving the way for image analysis to determine the underlying molecular makeup of the test samples.

Mechanism of streptomyces albidoflavus STV1572a derived 1-heneicosanol as an inhibitor against squalene epoxidase of Trichophyton mentagrophytes.

An increase in incidences of tinea infections paves the way to discover the novel antifungal drugs from unexplored natural resources. The quality of life in patients with tinea infection may be affected by different factors, including morbidity, length of illness, social and demographic factors. The present investigation explores the functional principle of a bioactive compound isolated from actinomycetes, S. albidoflavus STV1572a by in-silico and in-vitro studies. In continuation of our previous reports on the antidermatophytic potential of S. albidoflavus STV1572a, this study progresses with the in-silico molecular docking study of the seven GC-MS discovered ligands, and six dermatophytic modelled targets. Through virtual screening, it was revealed that a docking score -8.8 between 1-heneicosanol and squalene epoxidase favored partially in understanding the mode of action. Further validation of in-silico study was performed by a sterol quantification assay which confirmed the antidermatophytic mechanism of 1-heneicosanol. Taken together, the evidence from this study suggests that 1-heneicosanol has a potential antidermatophytic compound and can be considered for dermatophytic treatment.

Burn injury induces elevated inflammatory traffic: the role of NF-κB.

A burn insult generally sustains a hypovolemic shock due to a significant loss of plasma from the vessels. The burn injury triggers the release of various mediators, such as reactive oxygen species (ROS), cytokines, and inflammatory mediators. Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), stemming from foreign microbial discharge and damaged tissue or necrotic cells from the burn-injured site, enter the systemic circulation, activate toll-like receptors (TLRs), and trigger the excessive secretion of cytokines and inflammatory mediators. Inflammation plays a vital role in remodeling an injured tissue, detoxifying toxins, and helps in the healing process. A transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), contributes to a variety of physiological and pathological conditions, including immune response, cell death, cell survival, and inflammatory processes. During the pathogenesis of a burn wound, upregulation of various cytokines and growth factors lead to undesirable tissue inflammation. Thus, NF-κB, a dominant moderator of inflammation, needs to be altered to prove beneficial to the treatment of burns or other inflammation-associated diseases. This review addresses the relationship between NF-κB and elevated inflammation in a burn condition that could potentially be altered to induce an early wound-healing mechanism of burn wounds.

Plant-derived bioadhesives for wound dressing and drug delivery system.

Synthetic polymers have been widely used in various biomedical applications like drug delivery, wound dressing, etc. They pose a question of bio-compatibility and bio-accumulation, limiting to a minimum class of synthetic polymers to be efficient and versatile. Hence, one cheap and reliant replacement is the use of natural adhesives over the synthetic adhesive polymeric system. The pluripotency of plant could be exploit, making it a perfect candidate for extraction of plant-derived adhesives component for wound dressing and drug delivery system in large-scale production. Current advancement use excipients which influence, the rate of drug release and absorption. Properties like matrix formation and environment responsive gelation can be exploited through these plant-derived components for controlled drug release according to specific therapeutic requirement. This review explores such plant-derived bioactive component: Mucilage and gums, their isolation, and characterization which can be exploited as excipients in the formulation of drug delivery system as well as a wound dressing.