Attenuation of Las/Rhl quorum sensing regulated virulence and biofilm formation in Pseudomonas aeruginosa PAO1 by Artocarpesin.

The emergence of multidrug resistance and increased pathogenicity in microorganisms is conferred by the presence of highly synchronized cell density dependent signalling pathway known as quorum sensing (QS). The QS hierarchy is accountable for the secretion of virulence phenotypes, biofilm formation and drug resistance. Hence, targeting the QS phenomenon could be a promising strategy to counteract the bacterial virulence and drug resistance. In the present study, artocarpesin (ACN), a 6-prenylated flavone was investigated for its capability to quench the synthesis of QS regulated virulence factors. From the results, ACN showed significant inhibition of secreted virulence phenotypes such as pyocyanin (80%), rhamnolipid (79%), protease (69%), elastase (84%), alginate (88%) and biofilm formation (88%) in opportunistic pathogen, Pseudomonas aeruginosa PAO1. Further, microscopic observation of biofilm confirmed a significant reduction in biofilm matrix when P. aeruginosa PAO1 was supplemented with ACN at its sub-MIC concentration. Quantitative gene expression studies showed the promising aspects of ACN in down regulation of several QS regulatory genes associated with production of virulence phenotypes. Upon treatment with sub-MIC of ACN, the bacterial colonization in the gut of Caenorhabditis elegans was potentially reduced and the survival rate was greatly improved. The promising QS inhibition activities were further validated through in silico studies, which put an insight into the mechanism of QS inhibition. Thus, ACN could be considered as possible drug candidate targeting chronic microbial infections.

Effects of gut microbiome and obesity on the development, progression and prevention of cancer (Review).

Cancer is one of the leading causes of death worldwide and it is estimated that the mortality rate of cancer will increase in the coming years. The etiology of the development and progression of cancer is multifactorial. Insights have been gained on the association between the human microbiome and tumor cell malignancy. A number of commensal microbe species are present in the human gut. They serve pivotal roles in maintaining several health and disease conditions, such as inflammatory bowel disease, irritable bowel syndrome, obesity and diabetes. Known major factors involved in cancer development include age, hormone levels, alcohol consumption, diet, being overweight, obesity, and infections, regardless of the type of cancer. Therefore, the present review aims to discuss the relationship between the gut microbiome and obesity­associated malignancies, including colorectal, gastric and liver cancer. Obesity has been reported to contribute to the development of numerous types of cancer primarily caused by high fatty food intake. In addition, obesity­associated microbiome alterations can lead to cancer and its progression. Dysbiosis of the gut microbiota can alter the metabolite profile, whilst increasing the levels of toxins, such as Bacteroides fragilis toxin and colibactin and cytolethal distending toxin, which are responsible for oncogenesis. The present review provides insights into the impact of gut microbiome dysbiosis on the progression of different types of cancers associated with obesity. It also discusses possible strategies for preserving a healthy gut microbiome. Different pre­clinical and clinical models are available for studying cancer development downstream of gut microbiome dysbiosis. Furthermore, the role of metabolites or drugs employed in colorectal, gastric and liver cancer therapy would be discussed.

Cellular senescence in aging: Molecular basis, implications and therapeutic interventions.

Cellular senescence is an irreversible proliferation arrest in response to cellular damage and stress. Although cellular senescence is a highly stable cell cycle arrest, it can influence many physiological, pathological, and aging processes. Cellular senescence can be triggered by various intrinsic and extrinsic stimuli such as oxidative stress, mitochondrial dysfunction, genotoxic stress, oncogenic activation, irradiation and chemotherapeutic agents. Senescence is associated with several molecular and phenotypic alterations, such as senescence-associated secretory phenotype (SASP), cell cycle arrest, DNA damage response (DDR), senescence-associated ß-galactosidase, morphogenesis, and chromatin remodeling. Cellular senescence is a regular physiological event involved in tissue homeostasis, embryonic development, tissue remodeling, wound healing, and inhibition of tumor progression. Mitochondria are one of the organelles that undergo significant morphological and metabolic changes associated with senescence. Recent evidence unraveled that inter-organelle communication regulates cellular senescence, where mitochondria form a highly complex and dynamic network throughout the cytoplasm with other organelles, like the endoplasmic reticulum. An imbalance in organelle interactions may result in faulty cellular homeostasis, which contributes to cellular senescence and is associated with organ aging. Since mitochondrial dysfunction is a common characteristic of cellular senescence and age-related diseases, mitochondria-targeted senolytic or redox modulator senomorphic strategies help solve the complex problems with the detrimental consequences of cellular senescence. Understanding the regulation of mitochondrial metabolism would provide knowledge on effective therapeutic interventions for aging and age-related pathologies. This chapter focuses on the biochemical and molecular mechanisms of senescence and targeting senescence as a potential strategy to alleviate age-related pathologies and support healthy aging.

Bioactive molecules from haloarchaea: Scope and prospects for industrial and therapeutic applications.

Marine environments and salty inland ecosystems encompass various environmental conditions, such as extremes of temperature, salinity, pH, pressure, altitude, dry conditions, and nutrient scarcity. The extremely halophilic archaea (also called haloarchaea) are a group of microorganisms requiring high salt concentrations (2-6 M NaCl) for optimal growth. Haloarchaea have different metabolic adaptations to withstand these extreme conditions. Among the adaptations, several vesicles, granules, primary and secondary metabolites are produced that are highly significant in biotechnology, such as carotenoids, halocins, enzymes, and granules of polyhydroxyalkanoates (PHAs). Among halophilic enzymes, reductases play a significant role in the textile industry and the degradation of hydrocarbon compounds. Enzymes like dehydrogenases, glycosyl hydrolases, lipases, esterases, and proteases can also be used in several industrial procedures. More recently, several studies stated that carotenoids, gas vacuoles, and liposomes produced by haloarchaea have specific applications in medicine and pharmacy. Additionally, the production of biodegradable and biocompatible polymers by haloarchaea to store carbon makes them potent candidates to be used as cell factories in the industrial production of bioplastics. Furthermore, some haloarchaeal species can synthesize nanoparticles during heavy metal detoxification, thus shedding light on a new approach to producing nanoparticles on a large scale. Recent studies also highlight that exopolysaccharides from haloarchaea can bind the SARS-CoV-2 spike protein. This review explores the potential of haloarchaea in the industry and biotechnology as cellular factories to upscale the production of diverse bioactive compounds.

Surveillance and mitigation of soil pollution through metagenomic approaches.

Soil pollution is one of the serious global threats causing risk to environment and humans. The major cause of accumulation of pollutants in soil are anthropogenic activities and some natural processes. There are several types of soil pollutants which deteriorate the quality of human life and animal health. They are recalcitrant hydrocarbon compounds, metals, antibiotics, persistent organic compounds, pesticides and different kinds of plastics. Due to the detrimental properties of pollutants present in soil on human life and ecosystem such as carcinogenic, genotoxic and mutagenic effects, alternate and effective methods to degrade the pollutants are recommended. Bioremediation is an effective and inexpensive method of biological degradation of pollutants using plants, microorganisms and fungi. With the advent of new detection methods, the identification and degradation of soil pollutants in different ecosystems were made easy. Metagenomic approaches are a boon for the identification of unculturable microorganisms and to explore the vast bioremediation potential for different pollutants. Metagenomics is a power tool to study the microbial load in polluted or contaminated land and its role in bioremediation. In addition, the negative ecosystem and health effect of pathogens, antibiotic and metal resistant genes found in the polluted area can be studied. Also, the identification of novel compounds/genes/proteins involved in the biotechnology and sustainable agriculture practices can be performed with the integration of metagenomics.

Soil carries diverse microorganisms which maintain plant and soil health.The different types of recalcitrant soil pollutants affect the ecosystem and human health.Complex pollutants can be degraded through bioremediation using microorganisms/plantsMetagenomic approaches help to explore novel organisms and enzymes involved in bioremediation.

Loss of tRNA methyltransferase 9 and DNA damage response genes in yeast confers sensitivity to aminoglycosides.

tRNA methyltransferase 9 (Trm9)-catalysed tRNA modifications have been shown to translationally enhance the DNA damage response (DDR). Here, we show that Saccharomyces cerevisiae trm9Δ, distinct DNA repair and spindle assembly checkpoint (SAC) mutants are differentially sensitive to the aminoglycosides tobramycin, gentamicin and amikacin, indicating DDR and SAC activation might rely on translation fidelity, under aminoglycoside stress. Further, we report that the DNA damage induced by aminoglycosides in the base excision repair mutants ogg1Δ and apn1Δ is mediated by reactive oxygen species, which induce the DNA adduct 8-hydroxy deoxyguanosine. Finally, the synergistic effect of tobramycin and the DNA-damaging agent bleomycin to sensitize trm9Δ and the DDR mutants mlh1Δ, rad51Δ, mre11Δ and sgs1Δ at significantly lower concentrations compared with wild-type suggests that cells with tRNA modification dysregulation and DNA repair gene defects can be selectively sensitized using a combination of translation inhibitors and DNA-damaging agents.

Polymicrobial Infections and Biofilms: Clinical Significance and Eradication Strategies.

Biofilms are population of cells growing in a coordinated manner and exhibiting resistance towards hostile environments. The infections associated with biofilms are difficult to control owing to the chronicity of infections and the emergence of antibiotic resistance. Most microbial infections are contributed by polymicrobial or mixed species interactions, such as those observed in chronic wound infections, otitis media, dental caries, and cystic fibrosis. This review focuses on the polymicrobial interactions among bacterial-bacterial, bacterial-fungal, and fungal-fungal aggregations based on in vitro and in vivo models and different therapeutic interventions available for polymicrobial biofilms. Deciphering the mechanisms of polymicrobial interactions and microbial diversity in chronic infections is very helpful in anti-microbial research. Together, we have discussed the role of metagenomic approaches in studying polymicrobial biofilms. The outstanding progress made in polymicrobial research, especially the model systems and application of metagenomics for detecting, preventing, and controlling infections, are reviewed.

Metagenomic insights into taxonomic, functional diversity and inhibitors of microbial biofilms.

Microbial cells attached to inert or living surfaces adopt biofilm mode with self-produced exopolysaccharide matrix containing polysaccharides, proteins, and extracellular DNA, for protection from adverse external stimuli. Biofilms in hospitals and industries serve as a breeding ground for drug-resistant pathogens and ARG enrichment that are linked to pathogenicity and also impede industrial production process. Biofilm formation, including virulence and pathogenicity, is regulated through quorum sensing (QS), a means of bacterial cell to cell communication for cooperative physiological processes. Hence, QS inhibition through quorum quenching (QQ) is a feasible approach to inhibit biofilm formation. In contrast, biofilms have beneficial roles in promoting plant growth, biocontrol, and wastewater treatment. Furthermore, polymicrobial biofilms can harbour novel compounds and species of industrial and pharmaceutical interest. Hence, surveillance of biofilm microbiome structure and functional attributes is crucial to determine the extent of the risk it poses and to harness its bioactive potential. One of the most preferred approaches to delineate the microbiome is culture-independent metagenomics. In this context, this review article explores the biofilm microbiome in built and natural settings such as agriculture, household appliances, wastewater treatment plants, hospitals, microplastics, and dental biofilm. We have also discussed the recent reports on discoveries of novel QS and biofilm inhibitors through conventional, metagenomics, and machine learning approaches. Finally, we present biofilm-derived novel metagenome-assembled genomes (MAGs), genomes, and taxa of medical and industrial interest.

Alantolactone modulates the production of quorum sensing mediated virulence factors and biofilm formation in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen in immunocompromised patients and accounts for mortality worldwide. Quorum sensing (QS) and QS mediated biofilm formation of P. aeruginosa increase the severity of infection in the host. New and effective therapeutics are in high demand to eliminate Pseudomonas infections. The current study investigated the quorum quenching and biofilm inhibition properties of alantolactone (ATL) against P. aeruginosa PAO1. The production of key virulence factors and biofilm components were affected in bacteria when treated with sub-MIC of ATL and further validated by qRT-PCR studies. The anti-infective potential of ATL was corroborated in an in vivo model with improved survival of infected Caenorhabditis elegans and reduced bacterial colonization. In silico studies suggested the molecular interactions of ATL to QS proteins as stable. Finally, ATL was explored in the present study to inhibit QS pathways and holds the potential to develop into an effective anti-infective agent against P. aeruginosa.

Oxidative stress alleviating potential of galactan exopolysaccharide from Weissella confusa KR780676 in yeast model system.

In the present study, galactan exopolysaccharide (EPS) from Weissella confusa KR780676 was evaluated for its potential to alleviate oxidative stress using in vitro assays and in vivo studies in Saccharomyces cerevisiae (wild type) and its antioxidant (sod1∆, sod2∆, tsa1∆, cta2∆ and ctt1∆), anti-apoptotic (pep4∆ and fis1∆) and anti-aging (sod2∆, tsa1∆ and ctt1∆)) isogenic gene deletion mutants. Galactan exhibited strong DPPH and nitric oxide scavenging activity with an IC50 value of 450 and 138 µg/mL respectively. In the yeast mutant model, oxidative stress generated by H2O2 was extensively scavenged by galactan in the medium as confirmed using spot assays followed by fluorescencent DCF-DA staining and microscopic studies. Galactan treatment resulted in reduction in the ROS generated in the yeast mutant cells as demonstrated by decreased fluorescence intensity. Furthermore, galactan exhibited protection against oxidative damage through H2O2 -induced apoptosis inhibition in the yeast mutant strains (pep4∆ and fis1∆) leading to increased survival rate by neutralizing the oxidative stress. In the chronological life span assay, WT cells treated with galactan EPS showed 8% increase in viability whereas sod2∆ mutant showed 10-15% increase indicating pronounced anti-aging effects. Galactan from W. confusa KR780676 has immense potential to be used as a natural antioxidant for nutraceutical, pharmaceutical and food technological applications. As per our knowledge, this is the first report on in-depth assessment of in vivo antioxidant properties of a bacterial EPS in a yeast deletion model system.

Betulinic acid mitigates oxidative stress-mediated apoptosis and enhances longevity in the yeast Saccharomyces cerevisiae model.

Betulinic acid (BA), a pentacyclic triterpenoid found in certain plant species, has been reported to have several health benefits including antioxidant and anti-apoptotic properties. However, the mechanism by which BA confers these properties is currently unknown. Saccharomyces cerevisiae, a budding yeast with a short life cycle and conserved cellular mechanism with high homology to humans, was used as a model for determining the role of BA in aging and programmed cell death (PCD). Treatment with hydrogen peroxide (H2O2) exhibited significantly increased (30-35%) survivability of antioxidant (sod1Δ, sod2Δ, cta1Δ, ctt1Δ, and tsa1Δ) and anti-apoptotic (pep4Δ and fis1Δ) mutant strains when cells were pretreated with BA (30 µM) as demonstrated in spot and CFU (Colony forming units) assays. Measurement of intracellular oxidation level using the ROS-specific dye H2DCF-DA showed that all tested BA-pretreated mutants exhibited decreased ROS than the control when exposed to H2O2. Similarly, when mutant strains were pretreated with BA and then exposed to H2O2, there was reduced lipid peroxidation as revealed by the reduced malondialdehyde content. Furthermore, BA-pretreated mutant cells showed significantly lower apoptotic activity by decreasing DNA/nuclear fragmentation and chromatin condensation under H2O2-induced stress as determined by DAPI and acridine orange/ethidium bromide staining. In addition, BA treatment also extended the life span of antioxidant and anti-apoptotic mutants by ∼10-25% by scavenging ROS and preventing apoptotic cell death. Our overall results suggest that BA extends the chronological life span of mutant strains lacking antioxidant and anti-apoptotic genes by lowering the impact of oxidative stress, ROS levels, and apoptotic activity. These properties of BA could be further explored for its use as a valuable nutraceutical.

Evaluating the genetic basiss of anti-cancer property of Taxol in Saccharomyces cerevisiae model.

Taxol has been regarded as one of the most successful anti-cancer drugs identified from natural sources to date. Although Taxol is known to sensitize cells by stabilizing microtubules, its ability to cause DNA damage in peripheral blood lymphocytes and to induce oxidative stress and apoptosis indicates that Taxol may have other modes of cytotoxic action. This study focuses on identifying the additional targets of Taxol that may contribute to its multifaceted cell killing property, using Saccharomyces cerevisiae. We show that yeast oxidative stress response mutants (sod1Δ, tsa1Δ and cta1Δ) and DNA damage response mutants (mre11∆, sgs1∆ and sub1∆) are highly sensitive to Taxol. Our results also show that Taxol increases the level of reactive oxygen species (ROS) in yeast oxidative stress response mutant strains. Further, 4',6-Diamidino-2'-phenylindole (DAPI) and acridine orange/ethidium bromide (AO/EB) staining show that Taxol induces apoptotic features such as nuclear fragmentation and chromatin condensation in DNA repair mutants. On the whole, our results suggest that Taxol's cytotoxic property is attributed to its multifaceted mechanism of action. Yeast S. cerevisiae anti-oxidant and DNA repair gene mutants are sensitive to Taxol compared to wild-type, suggesting yeast model can be used to identify the genetic targets of anti-cancer drugs.

Sesamin and sesamolin rescues Caenorhabditis elegans from Pseudomonas aeruginosa infection through the attenuation of quorum sensing regulated virulence factors.

Pseudomonas aeruginosa is an opportunistic pathogen emerging as a public health threat owing to their multidrug resistance profiles. The quorum sensing systems of P. aeruginosa play a pivotal role in the regulation of virulence and act as the target for the development of alternative therapeutics. The study discussed about anti-quorum sensing and antibiofilm properties of lignans (sesamin and sesamolin) found in Sesamum indicum (L.) against P. aeruginosa. The effect of lignans, sesamin and sesamolin on LasR/RhlR mediated virulence factor production, biofilm formation and bacterial motility were studied. To elucidate the mechanism of action of lignans on QS pathways, QS gene expression and in depth in silico analysis were performed. Both the lignans exerted anti-quorum sensing activity at 75 µg/ml without affecting the growth of bacteria. SA and SO exhibited decreased production of virulence factors such as pyocyanin, proteases, elastase and chitinase. The important biofilm constituents of P. aeruginosa including alginate, exopolysaccharides and rhamnolipids were strongly affected by the lignans. Likewise, plausible mechanism of action of lignans were determined through the down regulation of QS regulated gene expression, molecular docking and molecular simulation studies. The in vitro analysis was supported by C. elegans infection model. SA and SO rescued pre-infected worms within 8 days of post infection and reduced the colonization of bacteria inside the intestine due to the anti-infective properties of lignans. The lignans exhibited profound action on Las pathway rather than Rhl which was elucidated through in vitro and in silico assays. In silico pharmacokinetic analysis portrayed the opportunities to employ ligands as potential therapeutics for human use. The deep insights into the anti-QS, anti-biofilm and mechanism of action of lignans can contribute to the development of novel anti-infectives against pseuodmonal infections.

Bacterial Biofilm Inhibition: A Focused Review on Recent Therapeutic Strategies for Combating the Biofilm Mediated Infections.

Biofilm formation is a major concern in various sectors and cause severe problems to public health, medicine, and industry. Bacterial biofilm formation is a major persistent threat, as it increases morbidity and mortality, thereby imposing heavy economic pressure on the healthcare sector. Bacterial biofilms also strengthen biofouling, affecting shipping functions, and the offshore industries in their natural environment. Besides, they accomplish harsh roles in the corrosion of pipelines in industries. At biofilm state, bacterial pathogens are significantly resistant to external attack like antibiotics, chemicals, disinfectants, etc. Within a cell, they are insensitive to drugs and host immune responses. The development of intact biofilms is very critical for the spreading and persistence of bacterial infections in the host. Further, bacteria form biofilms on every probable substratum, and their infections have been found in plants, livestock, and humans. The advent of novel strategies for treating and preventing biofilm formation has gained a great deal of attention. To prevent the development of resistant mutants, a feasible technique that may target adhesive properties without affecting the bacterial vitality is needed. This stimulated research is a rapidly growing field for applicable control measures to prevent biofilm formation. Therefore, this review discusses the current understanding of antibiotic resistance mechanisms in bacterial biofilm and intensely emphasized the novel therapeutic strategies for combating biofilm mediated infections. The forthcoming experimental studies will focus on these recent therapeutic strategies that may lead to the development of effective biofilm inhibitors than conventional treatments.

Repositioning antispasmodic drug Papaverine for the treatment of chronic myeloid leukemia.

BACKGROUND: Papaverine is a benzylisoquinoline alkaloid from the plant Papaver somniferum (Opium poppy). It is approved as an antispasmodic drug by the US FDA and is also reported to have anti-cancer properties. Here, Papaverine's activity in chronic myeloid leukemia (CML) is explored using Saccharomyces cerevisiae, mammalian cancer cell lines, and in silico studies. METHODS: The sensitivity of wild-type and mutant (anti-oxidant defense, apoptosis) strains of S. cerevisiae to the drug Papaverine was tested by colony formation, spot assays, and AO/EB staining. In vitro cytotoxic effect was investigated on HCT15 (colon), A549 (lung), HeLa (cervical), and K562 (Bcr-Abl positive CML), and RAW 264.7 cell lines; cell cycle, mitochondrial membrane potential, ROS detection analyzed in K562 cells using flow cytometry and apoptotic markers, Bcr-Abl signaling pathways examined by western blotting. Molecular docking and molecular dynamics simulation of Papaverine against the target Bcr-Abl were also carried out. RESULTS: Investigation in S. cerevisiae evidenced Papaverine induces ROS-mediated apoptosis. Subsequent in vitro examination showed that CML cell line K562 was more sensitive to the drug Papaverine. Papaverine induces ROS generation, promotes apoptosis, and inhibits Bcr-Abl downstream signaling. Papaverine acts synergistically with the drug Imatinib. Furthermore, the docking and molecular dynamic simulation studies supported that Papaverine binds to the allosteric site of Bcr-Abl. CONCLUSION: The data presented here have added support to the concept of polypharmacology of existing drugs and natural compounds to interact with more than one target. This study provides a proof-of-concept for repositioning Papaverine as an anti-CML drug.

Astaxanthin protects oxidative stress mediated DNA damage and enhances longevity in Saccharomyces cerevisiae.

Reactive oxygen species (ROS) have long been found to play an important role in oxidative mediated DNA damage. Fortunately, cells possess an antioxidant system that can neutralize ROS. However, oxidative stress occurs when antioxidants are overwhelmed by ROS or impaired antioxidant pathways. This study was carried out to find the protective effect of astaxanthin on the yeast DNA repair-deficient mutant cells under hydrogen peroxide stress. The results showed that astaxanthin enhances the percent cell growth of rad1∆, rad51∆, apn1∆, apn2∆ and ogg1∆ cells. Further, the spot test and colony-forming unit count results confirmed that astaxanthin protects DNA repair mutant cells from oxidative stress. The DNA binding property of astaxanthin studied by in silico and in vitro methods indicated that astaxanthin binds to the DNA in the major and minor groove, and that might protect DNA against oxidative stress induced by Fenton's reagent. The intracellular ROS, 8-OHdG level and the DNA fragmentation as measured by comet tail was reduced by astaxanthin under oxidative stress. Similarly, reduced nuclear fragmentation and chromatin condensation results suggest that astaxanthin might reduce apoptosis. Finally, we show that astaxanthin decreases the accumulation of mutation rate and enhances the longevity of DNA repair-deficient mutants' cells during a chronological lifespan.

Biogenic Silver Nanoparticles Decorated with Methylene Blue Potentiated the Photodynamic Inactivation of Pseudomonas aeruginosa and Staphylococcus aureus.

The persistence of multidrug resistance among microorganisms has directed a mandate towards a hunt for the development of alternative therapeutic modalities. In this context, antimicrobial photodynamic therapy (aPDT) is sprouted as a novel strategy to mitigate biofilms and planktonic cells of pathogens. Nanoparticles (NPs) are reported with unique intrinsic and antimicrobial properties. Therefore, silver NPs (AgNPs) were investigated in this study to determine their ability to potentiate the aPDT of photosensitizer against Staphylococcus aureus and Pseudomonas aeruginosa. Biologically synthesized AgNPs were surface coated with methylene blue (MB) and studied for their aPDT against planktonic cells and biofilms of bacteria. The nano-conjugates (MB-AgNPs) were characterized for their size, shape and coated materials. MB-AgNPs showed significant phototoxicity against both forms of test bacteria and no toxicity was observed in the dark. Moreover, activity of MB-AgNPs was comparatively higher than that of the free MB, which concludes that MB-AgNPs could be an excellent alternative to combat antibiotic resistant bacteria.

Nanoparticle-Mediated Drug Delivery for the Treatment of Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are one of the foremost causes of high morbidity and mortality globally. Preventive, diagnostic, and treatment measures available for CVDs are not very useful, which demands promising alternative methods. Nanoscience and nanotechnology open a new window in the area of CVDs with an opportunity to achieve effective treatment, better prognosis, and less adverse effects on non-target tissues. The application of nanoparticles and nanocarriers in the area of cardiology has gathered much attention due to the properties such as passive and active targeting to the cardiac tissues, improved target specificity, and sensitivity. It has reported that more than 50% of CVDs can be treated effectively through the use of nanotechnology. The main goal of this review is to explore the recent advancements in nanoparticle-based cardiovascular drug carriers. This review also summarizes the difficulties associated with the conventional treatment modalities in comparison to the nanomedicine for CVDs.

Magnolol protects Saccharomyces cerevisiae antioxidant-deficient mutants from oxidative stress and extends yeast chronological life span.

We investigated the protective effect of a natural polyphenol, magnolol, on Saccharomyces cerevisiae cells under oxidative stress, and during aging. Our results showed the sensitivity of S. cerevisiae antioxidant gene deficient mutants (sod1∆, sod2∆, cta1∆, ctt1∆, gtt2∆ and tsa1∆) against hydrogen peroxide (H2O2) and menadione stress was rescued by magnolol as demonstrated in spot and colony forming unit counts. Yeast cells pretreated with magnolol showed decreased intracellular oxidation, lipid peroxidation and an increased level of reduced glutathione. Further, SOD1, CTA1 and GTT2 gene expression was examined by reverse transcription-polymerase chain reaction, and was found that magnolol significantly attenuated the upregulation of SOD1 and CTA1 genes under oxidative stress. Finally, longevity of the wild type and sod1 mutant cells were extended by magnolol, and also enhance stress resistance against oxidant stress during chronological aging.

Astaxanthin supplementation reduces dichlorvos-induced cytotoxicity in Saccharomyces cerevisiae.

This study evaluates the protective effect of astaxanthin against dichlorvos cytotoxicity in yeast Saccharomyces cerevisiae. Dichlorvos induce a dose-dependent cytotoxicity in yeast cells, which is mediated by oxidative stress. Our experimental results showed pre-treatment with astaxanthin enhances cell viability by 20-30% in yeast cells exposed to dichlorvos. A decrease in DCF fluorescence intensity and lipid peroxidation, increased SOD activity, and glutathione levels in astaxanthin-treated cells indicate that astaxanthin protected the cells against dichlorvos-induced oxidative stress. Reduced chromatin condensation and nuclear fragmentation in astaxanthin pre-treated cells also indicate that astaxanthin rescued the cells from dichlorvos-induced apoptosis. Our overall results suggest that dichlorvos induces oxidative stress-mediated cytotoxicity in yeast cells, and that was rescued by astaxanthin pre-treatment.