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.

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.

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.

Bioactive Microbial Metabolites in Cancer Therapeutics: Mining, Repurposing, and Their Molecular Targets.

The persistence and resurgence of cancer, characterized by abnormal cell growth and differentiation, continues to be a serious public health concern critically affecting public health, social life, and the global economy. Hundreds of putative drug molecules of synthetic and natural origin were approved for anticancer therapy in the last few decades. Although conventional anticancer treatment strategies have promising aspects, several factors such as their limitations, drug resistance, and side effects associated with them demand more effort in repositioning or developing novel therapeutic regimens. The rich heritage of microbial bioactive components remains instrumental in providing novel avenues for cancer therapeutics. Actinobacteria, Firmicutes, and fungi have a plethora of bioactive compounds, which received attention for their efficacy in cancer treatment targeting different pathways responsible for abnormal cell growth and differentiation. Yet the full potential remains underexplored to date, and novel compounds from such microbes are reported regularly. In addition, the advent of computational tools has further augmented the mining of microbial secondary metabolites and identifying their molecular targets in cancer cells. Furthermore, the drug-repurposing strategy has facilitated the use of approved drugs of microbial origin in regulating cancer cell growth and progression. The wide diversity of microbial compounds, different mining approaches, and multiple modes of action warrant further investigations on the current status of microbial metabolites in cancer therapeutics. Hence, in this review, we have critically discussed the untapped potential of microbial products in mitigating cancer progression. The review also summarizes the impact of drug repurposing in cancer therapy and discusses the novel avenues for future therapeutic drug development against cancer.

Nanomaterials as Novel Cardiovascular Theranostics.

Cardiovascular diseases (CVDs) are a group of conditions associated with heart and blood vessels and are considered the leading cause of death globally. Coronary heart disease, atherosclerosis, myocardial infarction represents the CVDs. Since CVDs are associated with a series of pathophysiological conditions with an alarming mortality and morbidity rate, early diagnosis and appropriate therapeutic approaches are critical for saving patients' lives. Conventionally, diagnostic tools are employed to detect disease conditions, whereas therapeutic drug candidates are administered to mitigate diseases. However, the advent of nanotechnological platforms has revolutionized the current understanding of pathophysiology and therapeutic measures. The concept of combinatorial therapy using both diagnosis and therapeutics through a single platform is known as theranostics. Nano-based theranostics are widely used in cancer detection and treatment, as evident from pre-clinical and clinical studies. Nanotheranostics have gained considerable attention for the efficient management of CVDs. The differential physicochemical properties of engineered nanoparticles have been exploited for early diagnosis and therapy of atherosclerosis, myocardial infarction and aneurysms. Herein, we provided the information on the evolution of nano-based theranostics to detect and treat CVDs such as atherosclerosis, myocardial infarction, and angiogenesis. The review also aims to provide novel avenues on how nanotherapeutics' trending concept could transform our conventional diagnostic and therapeutic tools in the near future.

Anti-quorum sensing and anti-biofilm activity of 5-hydroxymethylfurfural against Pseudomonas aeruginosa PAO1: Insights from in vitro, in vivo and in silico studies.

Pseudomonas aeruginosa is one of the most common pathogens associated with nosocomial infections and a great concern to immunocompromised individuals especially in the cases of cystic fibrosis, AIDS and burn wounds. The pathogenicity of P. aeruginosa is largely directed by the quorum sensing (QS) system. Hence, QS may be considered an important therapeutic target to combat P. aeruginosa infections. The anti-quorum sensing and anti-biofilm efficacy of aromatic aldehyde, 5-hydroxymethylfurfural (5-HMF) against P. aeruginosa PAO1 were assessed. At the sub-inhibitory concentration, 5-HMF suppressed the production of QS-controlled virulence phenotypes and biofilm formation in P. aeruginosa. It was also able to significantly enhance the survival rate of C. elegans infected with P. aeruginosa. The in silico studies revealed that 5-HMF could serve as a competitive inhibitor for the auto-inducer molecules as it exhibited a strong affinity for the regulatory proteins of the QS-circuits i.e. LasR and RhlR. In addition, a significant down-regulation in the expression of QS-related genes was observed suggesting the ability of 5-HMF in mitigating the pathogenicity of P. aeruginosa.

Synthesis and antimicrobial photodynamic effect of methylene blue conjugated carbon nanotubes on E. coli and S. aureus.

Catheter-related bloodstream infections (CRBSIs) are one of the leading causes of high morbidity and mortality in hospitalized patients. The proper management, prevention and treatment of CRBSIs rely on the understanding of these highly resistant bacterial infections. The emergence of such a challenge to public health has resulted in the development of an alternative antimicrobial strategy called antimicrobial photodynamic therapy (aPDT). In the presence of a photosensitizer (PS), light of the appropriate wavelength, and molecular oxygen, aPDT generates reactive oxygen species (ROS) which lead to microbial cell death and cell damage. We investigated the enhanced antibacterial and antibiofilm activities of methylene blue conjugated carbon nanotubes (MBCNTs) on biofilms of E. coli and S. aureus using a laser light source at 670 nm with radiant exposure of 58.49 J cm-2. Photodynamic inactivation in test cultures showed 4.86 and 5.55 log10 reductions in E. coli and S. aureus, respectively. Biofilm inhibition assays, cell viability assays and EPS reduction assays showed higher inhibition in S. aureus than in E. coli, suggesting that pronounced ROS generation occurred due to photodynamic therapy in S. aureus. Results from a study into the mechanism of action proved that the cell membrane is the main target for photodynamic inactivation. Comparatively higher photodynamic inactivation was observed in Gram positive bacteria due to the increased production of free radicals inside these cells. From this study, we conclude that MBCNT can be used as a promising nanocomposite for the eradication of dangerous pathogens on medical devices.

Green Synthesized Nanomaterials as Theranostic Platforms for Cancer Treatment: Principles, Challenges and the Road Ahead.

With the emergence of nanotechnology, new methods have been developed for engineering various nanoparticles for biomedical applications. Nanotheranostics is a burgeoning research field with tremendous prospects for the improvement of diagnosis and treatment of various cancers. However, the development of biocompatible and efficient drug/gene delivery theranostic systems still remains a challenge. Green synthetic approach of nanoparticles with low capital and operating expenses, reduced environmental pollution and better biocompatibility and stability is a latest and novel field, which is advantageous over chemical or physical nanoparticle synthesis methods. In this article, we summarize the recent research progresses related to green synthesized nanoparticles for cancer theranostic applications, and we also conclude with a look at the current challenges and insight into the future directions based on recent developments in these areas.

Evaluation of in vivo antioxidant potential of Syzygium jambos (L.) Alston and Terminalia citrina Roxb. towards oxidative stress response in Saccharomyces cerevisiae.

Excessive production and restricted elimination of free radicals like superoxide, hydroxyl radical (·OH), anion radical (O2 ·-), and non-radical hydrogen peroxide (H2O2) are related to the development of cancer, arteriosclerosis, arthritis and neurodegenerative diseases. According to a report of World Health Organisation, about 80% of the population living in the developing countries predominantly depends on the traditional medicine for their primary healthcare. Plants possess innate ability to synthesize a wide variety of enzymatic and non-enzymatic antioxidants capable of attenuating ROS-induced oxidative damage. The ethanolic leaf extracts of Syzygium jambos L. and Terminalia citrina Roxb. exhibited a significant in vitro antioxidant activity when compared with natural antioxidant, ascorbic acid. The extracts also provided strong cellular protection against the damaging effects of H2O2 induced oxidative stress in the mutant strains (tsa1Δ and sod1Δ) of Saccharomyces cerevisiae. The GC-MS analysis of the leaf extracts revealed the presence of phytoconstituents majorly constituting of terpenes, vitamin and fatty acids contributing to the antioxidant property. The plant extracts may serve as a potential source of exogenous antioxidants to combat the undesirable effects of oxidative stress.

Functional probes for cardiovascular molecular imaging.

Cardiovascular diseases (CVDs) are a severely threatening disorder and frequently cause death in industrialized countries, posing critical challenges to modern research and medicine. Molecular imaging has been heralded as the solution to many problems encountered in individuals living with CVD. The use of probes in cardiovascular molecular imaging is causing a paradigmatic shift from regular imaging techniques, to future advanced imaging technologies, which will facilitate the acquisition of vital information at the cellular and molecular level. Advanced imaging for CVDs will help early detection of disease development, allow early therapeutic intervention, and facilitate better understanding of fundamental biological processes. To promote a better understanding of cardiovascular molecular imaging, this article summarizes the current developments in the use of molecular probes, highlighting some of the recent advances in probe design, preparation, and functional modification.

Determination of Antioxidant Potential of Selected Wild Edible Mushrooms from India in a Saccharomyces cerevisiae Model System.

Wild edible mushrooms are one of the most fascinating nutraceuticals because of their pleasant texture, peculiar aroma, and tremendous therapeutic potential; they have been used since ancient times. In this study we evaluated the antioxidant potential of 4 wild edible mushrooms-Cantharellus tropicalis, C. cibarius, Lentinus edodes, and Russula delica-collected from Mizoram, India. We performed in vitro and in vivo studies using a Saccharomyces cerevisiae stress response mechanism as the model system. Among the 4 mushrooms, C. cibarius exhibited the most significant antioxidant activity both in vitro and in vivo, followed by L. edodes, R. delica, and C. tropicalis. Gas chromatography-mass spectrometry analysis of methanolic extracts of the mushrooms revealed the presence of substantial amounts of fatty acids, fatty acid esters, and other bioactive constituents. The in vitro antioxidant activity was corroborated by in vivo studies using an S. cerevisiae oxidative stress response mechanism. In spot assays, the C. cibarius methanolic extract showed the highest scavenging potential in wild and mutant (sodlΔ and tsalΔ) strains of S. cerevisiae. These results were confirmed further by determining the level of reactive oxygen species through the use of fluorescent microscopy and intensity studies. The results suggested the efficacy of wild edible mushrooms as prominent therapeutic agents and that they have tremendous nutraceutical properties.

Attenuation of quorum sensing controlled virulence factors and biofilm formation in Pseudomonas aeruginosa by pentacyclic triterpenes, betulin and betulinic acid.

The production of virulence determinants and biofilm formation in numerous pathogens is regulated by the cell-density-dependent phenomenon, Quorum sensing (QS). The QS system in multidrug resistant opportunistic pathogen, P. aeruginosa constitutes of three main regulatory circuits namely Las, Rhl, and Pqs which are closely linked to its pathogenicity and establishment of chronic infections. In spite intensive antibiotic therapy, P. aeruginosa continue to be an important cause of nosocomial infections and also the major cause of mortality in Cystic Fibrosis patients with 80% of the adults suffering from chronic P. aeruginosa infection. Hence, targeting QS circuit offers an effective intervention to the ever increasing problem of drug resistant pathogens. In the present study, the pentacyclic triterpenes i.e. Betulin (BT) and Betulinic acid (BA) exhibited significant attenuation in production of QS-regulated virulence factors and biofilm formation in P. aeruginosa, at the sub-lethal concentration. The test compound remarkably interfered in initial stages of biofilm development by decreasing the exopolysaccharide production and cell surface hydrophobicity. Based on the in vivo studies, the test compounds notably enhanced the survival of Caenorhabditis elegans infected with P. aeruginosa. Furthermore, molecular docking analysis revealed that BT and BA can act as a strong competitive inhibitor for QS receptors, LasR and RhlR. The findings suggest that BT and BA can serve as potential anti-infectives in the controlling chronic infection of P. aeruginosa.

Green synthesis of anisotropic gold nanoparticles using hordenine and their antibiofilm efficacy against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a notorious pathogen that causes biofilm aided infections in patients with cystic fibrosis and burn wounds, resulting in significant mortality in immunocompromised individuals. This study reports a novel one-step biosynthesis of gold nanoparticles using phytocompound, hordenine (HD), as a reducing and capping agent. The synthesis of the anisotropic hordenine-fabricated gold nanoparticles (HD-AuNPs) with an average particle size of 136.87 nm was achieved within 12 h of incubation at room temperature. Both HD and HD-AuNPs exhibited significant antibiofilm activity against P. aeruginosa PAO1, although greater biofilm inhibition was observed for the nanoparticles as compared to hordenine alone. In the microtitre plate assay and tube method, the nanoparticles significantly inhibited the biofilm formation by 73.69 and 78.41%, respectively. The exopolysaccharide production by the test pathogen was arrested by 68.46% on treatment with the nanoparticles. Further, the effect of HD and HD-AuNPs on the biofilm architecture of P. aeruginosa was revealed by light and confocal laser-scanning microscopy micrographs. The overall results of this study suggested the synergistic antibiofilm effect of AuNPs and HD for the treatment of chronic bacterial infections caused by biofilms forming pathogens.

Indolylmethylene benzo[h]thiazolo[2,3-b]quinazolinones: synthesis, characterization and evaluation of anticancer and antimicrobial activities.

A series of novel 10-((1H-indol-3-yl)methylene)-7-aryl-7,10-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-9(6H)-ones (8a-t) have been synthesized in good yields by the reaction of benzo[h]quinazoline-2(1H)-thiones (4a-f) with 2-chloro-N-phenylacetamide (5) followed by Knoevenagel condensation with various indole-3-carbaldehydes (7a-d) under conventional method. All the synthesized compounds were characterized by spectral studies and screened for their in vitro anticancer and antimicrobial activities. Compound 8c has exhibited excellent activity against MCF-7 (breast cancer cell line) than the standard drug Doxorubicin. Compound 8d against both the cancer cell lines, 8q against MCF-7 and 8c, 8h against HepG2 have also shown good activity. Remaining compounds have shown moderate activity against both the cell lines. Antimicrobial activity revealed that, the compound 8q and 8t against Staphylococcus aureus and 8i, 8k, 8l, 8q &8t against Klebsiella pneumoniae have shown equipotent activity on comparing with the standard drug Streptomycin. Remaining compounds have shown significant antibacterial and comparable antifungal activities against all the tested microorganisms.