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Ensete superbum Roxb. Cheesman (wild banana) is a plant traditionally used for the treatment of fever and diarrhea. On a preliminary screening, the ripe peel aqueous extract (PA) exhibited higher cytotoxicity (cell viability of 49% against HCT-15 at 75 µg/ml; and 46% against Caco2 at 50 µg/ml), superior anti-inflammatory (IC 50 of 0.49 µg/ml), and greater anti-mutagenic activity at 500 µg/plate compared to the aqueous extracts of seed (SA), flower (FA) and bract (BA). Therefore, we further evaluated the anti-proliferative activity of PA and its fractions. The ability to inhibit the growth of cell lines (HCT-15 and Caco2) was used for the bio-guided fractionation and isolation of active compounds in PA using chromatographic techniques. Multiple extractions of the PA yielded the peel dioxane fraction (PD), and column fractionation of PD yielded eight compounds, of which three (Compound D-PDD, Compound E-PDE, and Compound G-PDG) possessed higher cytotoxic activity. At 10 µg/ml, the cell viability of HCT-15 was 50.1%, 46.5%, and 61.9%, respectively; Caco2 was 98.2%, 62.9%, and 64.7%, respectively, for PDD, PDE, and PDG. These compounds also showed apoptotic effect as evidenced by measuring the mitochondrial membrane potential, dual staining (acridine orange/ethidium bromide), DNA fragmentation, and the ROS status in colorectal cell lines. The UPLC-HRMS/MS, FTIR, and NMR data revealed the active compounds as quercetin-3-O-rutinoside, 3,5-dimethoxy-4-hydroxybenzoic acid, and 4',5,7-trihydroxyflavone. These findings indicate the anti-proliferative potential of PA, and warrant further investigation of its active principles in the amelioration of colorectal cancer in in vivo models. PRACTICAL APPLICATION: The potential of an underutilized crop as a source of therapeutic agents for colon cancer was established, as the study showed a high cytotoxic activity of wild bananas against HCT-15 and Caco2 cell lines. Bioactivity guided fractionation of peel fraction identified the active compounds present in wild banana, and their anticancer activity was attributed to the induction of cell death. The study indicated that wild banana has the potential to inhibit the growth of colon cancer cells., (© 2021 Institute of Food Technologists®.)

Oral cavity squamous cell carcinoma (OCSCC) is the most common malignancy of the oral cavity. The substantial risk factors for OCSCC are the consumption of tobacco products, alcohol, betel quid, areca nut, and genetic alteration. However, technological advancements have occurred in treatment, but the survival decreases with late diagnosis; therefore, new methods are continuously being investigated for treatment. In addition, the rate of secondary tumor formation is 3-7% yearly, which is incomparable to other malignancies and can lead to the disease reoccurrence. Oral cavity cancer (OCC) arises from genetic alterations, and a complete understanding of the molecular mechanism involved in OCC is essential to develop targeted treatments. This review aims to update the researcher on oral cavity cancer, risk factors, genetic alterations, molecular mechanism, classification, diagnostic approaches, and treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A sparse number of available antifungal drugs, therapeutic side effects, and drug resistance are major challenges in current antifungal therapy to treat Candida albicans-associated infections. Here, we describe two food-derived yeasts, Saccharomyces cerevisiae and Issatchenkia occidentalis, that inhibit virulence traits of C. albicans, including hyphal morphogenesis, biofilm formation, and adhesion to intestinal epithelial cells. These yeasts also protect the model host Caenorhabditis elegans from C. albicans infection. We demonstrate that the protective activity is primarily retained in the secretome of the beneficial yeasts, and the protection they provide as a physical barrier is negligible. S. cerevisiae aro8 aro9 mutant analysis demonstrate that phenylethanol and tryptophol are necessary for protection, and experiments with commercially procured compounds indicate that they are sufficient to inhibit C. albicans virulence. We propose food-derived yeasts as an alternative or combination therapy to conventional antifungal therapy for C. albicans infection. IMPORTANCE The gut microbiome, primarily established by food, is complex and contributes to the health of the host. Molecular mechanisms that regulate microbial interactions and host health remain unclear. Here, we show that the pathogen C. albicans interacts with food-derived beneficial yeasts in the gut of the microscopic worm, C. elegans, forming a simple microbiome. C. albicans can colonize the worm gut, compromising the worm's health, and exposure to the food-derived yeasts ameliorates this effect protecting the nematode host. We identify small molecules from food-derived yeasts that are necessary and sufficient to inhibit multiple virulence traits of C. albicans and protect the nematode host. The nematode gut faithfully recapitulates a mammalian intestine. This could be an effective alternative or combination therapy for C. albicans infection.

Nanoparticles (NPs) synthesized by laser ablation in distilled water were used to study their biological effect on normal and cancer cells. Parameters such as cell morphology, cell proliferation and viability were examined for treated cell lines, and the effect was represented in terms of cells cytotoxicity using standard procedures. The study reveals the higher cytotoxic effect of nanoparticles on cancerous cells of breast, melanoma and colon origin compared to normal fibroblast cells NIH- 3T3. Furthermore, DNA fragmentation assay results demonstrated the apoptosis mediated cell death in nanoparticle-treated cancer cells. The distinct role of nanoparticles in normal and cancer cells of different origin showed that nanoparticles were specific to cause cytotoxicity in particular cancer cells type. NPs exhibit cytotoxic effects in cancer cells by inducing apoptosis. These studies provide fundamental evidence for the easy, simple and safe mode of nanoparticles synthesis and their application in cancer cells death.

Systemic infections of Candida species pose a significant threat to public health. Toxicity associated with current therapies and emergence of resistant strains present major therapeutic challenges. Here, we report exploitation of the probiotic properties of two novel, food-derived yeasts, Saccharomyces cerevisiae (strain KTP) and Issatchenkia occidentalis (strain ApC), as an alternative approach to combat widespread opportunistic fungal infections. Both yeasts inhibit virulence traits such as adhesion, filamentation, and biofilm formation of several non- albicans Candida species, including Candida tropicalis , Candida krusei , Candida glabrata , and Candida parapsilosis as well as the recently identified multidrug-resistant species Candida auris They inhibit adhesion to abiotic surfaces as well as cultured colon epithelial cells. Furthermore, probiotic treatment blocks the formation of biofilms of individual non- albicans Candida strains as well as mixed-culture biofilms of each non- albicans Candida strain in combination with Candida albicans The probiotic yeasts attenuated non- albicans Candida infections in a live animal. In vivo studies using Caenorhabditis elegans suggest that exposure to probiotic yeasts protects nematodes from infection with non- albicans Candida strains compared to worms that were not exposed to the probiotic yeasts. Furthermore, application of probiotic yeasts postinfection with non- albicans Candida alleviated pathogenic colonization of the nematode gut. The probiotic properties of these novel yeasts are better than or comparable to those of the commercially available probiotic yeast Saccharomyces boulardii , which was used as a reference strain throughout this study. These results indicate that yeasts derived from food sources could serve as an effective alternative to antifungal therapy against emerging pathogenic Candida species. IMPORTANCE Non- albicans Candida -associated infections have emerged as a major risk factor in the hospitalized and immunecompromised patients. Besides, antifungal-associated complications occur more frequently with these non- albicans Candida species than with C. albicans Therefore, as an alternative approach to combat these widespread non- albicans Candida -associated infections, here we showed the probiotic effect of two yeasts, Saccharomyces cerevisiae (strain KTP) and Issatchenkia occidentalis (ApC), in preventing adhesion and biofilm formation of five non- albicans Candida strains, Candida tropicalis , Candida krusei , Candida glabrata , Candida parapsilosis , and Candida auris The result would influence the current trend of the conversion of conventional antimicrobial therapy into beneficial probiotic microbe-associated antimicrobial treatment., (Copyright © 2019 Kunyeit et al.)

Targeted degrading Aspergillus niger-derived prolyl endopeptidase (AN-PEP) is promising in gluten hydrolysis because it specifically cleaves the proline-rich sites in gluten. The current study aims to understand the safety aspects of AN-PEP hydrolysed low immunoreactive wheat flours by testing immune responses using cell line and animal models. In the AN-PEP hydrolysed wheat flour (AN-PEP HWF) gliadin extract, there was no increase in the levels of zonulin-1 (Zo-1) and pro-inflammatory cytokines (IL-6 and IL-8) but a significant increase was noted in the control wheat flour (CWF) gliadin-treated Caco-2 cells. The Zo-1 localization in Caco-2 cells was significantly noted in the reacted positive fluorescence cells that were treated with the control wheat flour. Further, a safety evaluation of HWF was carried out in gluten-sensitized BALB/c mice. Mouse anti-gliadin (IgG, IgA and IgE) antibodies were significantly generated in the CWF treated animals rather than the AN-PEP HWF groups. The serum pro-inflammatory (IL-1β, IL-4, IL-6, IL-15, TNF-α and IFN-γ) markers were observed in significant levels in CWF challenged mice and a similar trend was observed in ex-vivo splenocyte cells. A small intestine histopathological sectioning revealed that there are no abnormalities or structural changes in AN-PEP HWF challenged mice., (Copyright © 2019. Published by Elsevier Ltd.)

Aims: This study aimed at characterizing the adhesion and immune-stimulatory properties of native probiotic Lactobacillus fermentum (MCC 2759 and MCC 2760) and Lactobacillus delbrueckii MCC 2775., Methods and Results: Adhesion of the strains was assessed in Caco-2 and HT-29 cell lines. Expression of adhesion and immune markers were evaluated in Caco-2 cells by real-time qPCR. The cultures displayed >80% of adhesion to both cell lines and also induced the expression of mucin-binding protein (mub) gene in the presence of mucin, bile and pancreatin. Adhesion was mediated by carbohydrate and proteinaceous factors. The cultures stimulated the expression of inflammatory cytokines in Caco-2 cells. However, pro-inflammatory genes were down-regulated upon challenge with lipopolysaccharide and IL-10 was up-regulated by the cultures. Cell wall extract of L. fermentum MCC 2760 induced the expression of IL-6 by 5·47-fold, whereas crude culture filtrate enhanced the expression of IL-10 by 14·87-fold compared to LPS control., Conclusions: The bacterial cultures exhibited strong adhesion and anti-inflammatory properties., Significance and Impact of the Study: This is the first report to reveal the role of adhesion markers of L. fermentum and L. delbrueckii by qPCR. The strain-specific anti-inflammatory property of native cultures may be useful to alleviate inflammatory conditions and develop a target-based probiotic., (© 2018 The Society for Applied Microbiology.)

Gluten-related diseases such as wheat allergy, celiac disease, and gluten intolerance are widespread around the globe to genetically predisposed individuals. The present study aims to develop a wheat-gluten induced BALB/c murine model for addressing wheat-gluten related disorders by sensitizing the wheat gluten through the route of intraperitoneal and oral challenge in prolonged days. During the sensitization, the sera were collected for specific antigliadin antibodies response and proinflammatory markers quantification. Ex vivo primary cells and organs were collected for subsequent analysis of inflammatory profile. Prolonging sensitization of gluten can moderate the antigen-specific inflammatory markers such as IL-1β, IL-4, IL-15, IL-6, IFN-γ and TNF-α levels in mice sera. However, ex vivo primary cells of splenocytes (SPLs) and intestinal epithelial lymphocytes (IELs) significantly increased the IL-6, IL-15, IL-1β, and IL-4 levels in G+ (gliadin and gluten) treated cells. Histopathology staining of jejunum sections indicates enterocyte degeneration in the apical part of villi and damage of tight junctions in G+ (gliadin and gluten) sensitized murine model. Immunohistochemistry of embedded jejunum sections showed significant expression of positive cells of IL-15, tTG and IL-4 in G+ sensitized murine model. In contrast, all markers of gluten-related disorders are expressed exclusively such as tTG, ZO-1, IL-15, IL-6, IL-4, and intestinal inflammation was mediated by iNOS, COX-2, TLR-4 and NF- k Bp50 signaling mechanism in G+ sensitized mice.

Sesamol, the phenolic degradation product of sesamolin, although recognised for its anti-inflammatory effects, has low bioavailability. In this manuscript, we attempted to improve its bioavailability by encapsulation in mixed phosphatidylcholine micelles. Sesamol could be solubilised and entrapped in phosphatidylcholine mixed micelles (PCS) with 96.8% efficiency (particle size 3.0±0.06nm). Fluorescence spectra of PCS revealed lower relative fluorescence intensity (RFI 112) compared to 'free' sesamol (FS) (RFI 271). The bioaccessibility, transport across a monolayer of cells and cellular uptake of PCS was 8.58%, 1.5-fold and 1.2-fold better, respectively, compared to FS. The anti-inflammatory effects of FS and PCS were compared using LPS treated RAW 264.7 cell line and lipoxygenase inhibition. PCS effected downregulation of iNOS protein expression (27%), NO production (20%), ROS (32%) and lipoxygenase inhibition (IC 50 =31.24μM) compared to FS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aflatoxin B 1 (AFB 1 ) is one of the predominant mycotoxin contaminant in food and feed, causing oxidative stress and hepatotoxicity. Ginger phenolics have been reported for its antioxidant potential and hepatoprotective activity. The present study investigated the protective effects of phenolics rich ginger extract (GE) against AFB 1 induced oxidative stress and hepatotoxicity, in vitro and in vivo. The phenolic acid profiles of GE showed 6-gingerol and 6-shogaol as predominant components. Pretreatment of HepG2 cells with GE significantly inhibited the production of intracellular reactive oxygen species (ROS), DNA strand break, and cytotoxicity induced by AFB 1 . A comparable effect was observed in in vivo. Male Wistar rats were orally treated with GE (100 and 250mg/kg) daily, with the administration of AFB 1 (200μg/kg) every alternative day for 28days. Treatment with GE significantly reduced AFB 1 induced toxicity on the serum markers of liver damage. In addition, GE also showed significant hepatoprotective effect by reducing the lipid peroxidation and by enhancing the antioxidant enzymes activities. These results combined with liver histopathological observations indicated that GE has potential protective effect against AFB 1 induced hepatotoxicity. Additionally, administration of GE up-regulated Nrf2/HO-1 pathway, which further proved the efficiency of GE to inhibit AFB 1 induced hepatotoxicity., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: The laying hen model of spontaneous epithelial ovarian cancer (EOC) is unique in that it is the only model that enables observations of early events in disease progression and is therefore also uniquely suited for chemoprevention trials. Previous studies on the effect of dietary flaxseed in laying hens have revealed the potential for both amelioration and prevention of ovarian cancer. The objective of this study was to assess the effect of flaxseed on genes and pathways that are dysregulated in tumors. We have used a bioinformatics approach to identify these genes, followed by qPCR validation, immunohistochemical localization, and in situ hybridization to visualize expression in normal ovaries and tumors from animals fed a control diet or a diet containing 10% flaxseed., Results: Bioinformatic analysis of ovarian tumors in hens led to the identification of a group of highly up-regulated genes that are involved in the embryonic process of branching morphogenesis. Expression of these genes coincides with expression of E-cadherin in the tumor epithelium. Levels of expression of these genes in tumors from flax-fed animals are reduced 40-60%. E-cadherin and miR200 are both up-regulated in tumors from control-fed hens, whereas their expression is decreased 60-75% in tumors from flax-fed hens. This does not appear to be due to an increase in ZEB1 as mRNA levels are increased five-fold in tumors, with no significant difference between control-fed and flax-fed hens., Conclusions: We suggest that nutritional intervention with flaxseed targets the pathways regulating branching morphogenesis and thereby alters the progression of ovarian cancer.

Background: An effective way to control cancer is by prevention. Ovarian cancer is the most lethal gynecological malignancy. Progress in the treatment and prevention of ovarian cancer has been hampered due to the lack of an appropriate animal model and absence of effective chemo-prevention strategies. The domestic hens spontaneously develop ovarian adenocarcinomas that share similar histological appearance and symptoms such as ascites and metastasis with humans. There is a link between chronic inflammation and cancer. Prostaglandin E2 (PGE2) is the most pro-inflammatory ecoisanoid and one of the downstream products of two isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. PGE2 exerts its effects on target cells by coupling to four subtypes of receptors which have been classified as EP1-4. Fish oil is a source of omega-3 fatty acids (OM-3FAs) which may be effective in prevention of ovarian cancer. Our objective was to assess the potential impact of fish oil on expression of COX enzymes, PGE2 concentration, apoptosis and proliferation in ovaries of laying hens., Methods: 48 white Leghorn hens were fed 50, 100, 175, 375 and 700 mg/kg fish oil for 21 days. The OM3-FAs and omega-6 fatty acids contents of egg yolks were determined by Gas Chromatography. Proliferation, apoptosis, COX-1, COX-2 and prostaglandin receptor subtype 4 (EP4) protein and mRNA expression and PGE2 concentration in ovaries were measured by PCNA, TUNEL, Western blot, quantitative real-time qPCR and ELISA, respectively., Results: Consumption of fish oil increased the incorporation of OM-3FAs into yolks and decreased both COX-1 and COX-2 protein and mRNA expression. In correlation with COXs down-regulation, fish oil significantly reduced the concentrations of PGE2 in ovaries. EP4 protein and mRNA expression in ovaries of hens was not affected by fish oil treatment. A lower dose of fish oil increased the egg laying frequency. 175 and 700 mg/kg fish oil reduced proliferation and 700 mg/kg increased apoptosis in hen ovaries., Conclusions: Our findings suggest that the lower doses of fish oil reduce inflammatory PG and may be an effective approach in preventing ovarian carcinogenesis. These findings may provide the basis for clinical trials utilizing fish oil as a dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer.

The transcriptional repressors Snail and Slug contribute to cancer progression by mediating epithelial-mesenchymal transition (EMT), which results in tumor cell invasion and metastases. We extend this current understanding to demonstrate their involvement in the development of resistance to radiation and paclitaxel. The process is orchestrated through the acquisition of a novel subset of gene targets that is repressed under conditions of stress, effectively inactivating p53-mediated apoptosis, while another subset of targets continues to mediate EMT. Repressive activities are complemented by a concurrent derepression of specific genes resulting in the acquisition of stem cell-like characteristics. Such cells are bestowed with three critical capabilities, namely EMT, resistance to p53-mediated apoptosis, and a self-renewal program, that together define the functionality and survival of metastatic cancer stem cells. EMT provides a mechanism of escape to a new, less adverse niche; resistance to apoptosis ensures cell survival in conditions of stress in the primary tumor; whereas acquisition of "stemness" ensures generation of the critical tumor mass required for progression of micrometastases to macrometastases. Our findings, besides achieving considerable expansion of the inventory of direct genes targets, more importantly demonstrate that such elegant cooperative modulation of gene regulation mediated by Snail and Slug is critical for a cancer cell to acquire stem cell characteristics toward resisting radiotherapy- or chemotherapy-mediated cellular stress, and this may be a determinative aspect of aggressive cancer metastases.

The cellular mechanisms underlying the increasing aggressiveness associated with ovarian cancer progression are poorly understood. Coupled with a lack of identification of specific markers that could aid early diagnoses, the disease becomes a major cause of cancer-related mortality in women. Here we present direct evidence that the aggressiveness of human ovarian cancer may be a result of transformation and dysfunction of stem cells in the ovary. A single tumorigenic clone was isolated among a mixed population of cells derived from the ascites of a patient with advanced ovarian cancer. During the course of the study, yet another clone underwent spontaneous transformation in culture, providing a model of disease progression. Both the transformed clones possess stem cell-like characteristics and differentiate to grow in an anchorage-independent manner in vitro as spheroids, although further maturation and tissue-specific differentiation was arrested. Significantly, tumors established from these clones in animal models are similar to those in the human disease in their histopathology and cell architecture. Furthermore, the tumorigenic clones, even on serial transplantation continue to establish tumors, thereby confirming their identity as tumor stem cells. These findings suggest that: (a) stem cell transformation can be the underlying cause of ovarian cancer and (b) continuing stochastic events of stem and progenitor cell transformation define the increasing aggression that is characteristically associated with the disease.

Objectives: The transcriptional factors Snail and Slug have been reported to be important in cell migration during development and also during tumor metastasis. Their expression and role in ovarian cancer, hitherto unexplored, was examined to understand the molecular events in ovarian cancer metastases since the latter is responsible for the high degree of mortality associated with the disease., Methods: Ectopic expression of mSnail and mSlug in the epithelial ovarian cancer cell line SKOV3 was carried out and stable clones were selected. These were used to examine specific repression of the adherens, tight and desmosomal junction components by the two transcription factors. Furthermore, functional implications with respect to enhanced migration of cells, tumorigenecity and metastasis were also studied., Results: The ectopic expression of Snail or Slug resulted in epithelial-mesenchymal transition (EMT), enhanced motility, invasiveness and tumorigenecity in the cell line SKOV3. In addressing the mechanism by which Snail and Slug lead to loss of intercellular adhesion, specific repression of adherens junction components (E-cadherin and betacatenin), tight junction components (Occludin and ZO-1) and desmosomal junction components (Dsg2) were observed. Snail suppresses expression of adherens and tight junction components, while Slug suppresses expression of all the three junction components; concertedly, bringing down the intercellular adhesion between cells. Further activation of these transcriptional factors in hypoxic conditions revealed a rapid upregulation of Slug expression as an immediate reaction that probably triggers off a signaling cascade leading to Snail expression., Conclusions: These results indicate distinct roles of the transcriptional factors Snail and Slug during ovarian cancer metastasis and cell survival through mediation of EMT.