Cancer Insurgence Research Articles

Nanotechnology and Cancer Bioelectricity: Bridging the Gap Between Biology and Translational Medicine.

Bioelectricity is the electrical activity that occurs within living cells and tissues. This activity is critical for regulating homeostatic cellular function and communication, and disruptions of the same can lead to a variety of conditions, including cancer. Cancer cells are known to exhibit abnormal electrical properties compared to their healthy counterparts, and this has driven researchers to investigate the potential of harnessing bioelectricity as a tool in cancer diagnosis, prognosis, and treatment. In parallel, bioelectricity represents one of the means to gain fundamental insights on how electrical signals and charges play a role in cancer insurgence, growth, and progression. This review provides a comprehensive analysis of the literature in this field, addressing the fundamentals of bioelectricity in single cancer cells, cancer cell cohorts, and cancerous tissues. The emerging role of bioelectricity in cancer proliferation and metastasis is introduced. Based on the acknowledgement that this biological information is still hard to access due to the existing gap between biological findings and translational medicine, the latest advancements in the field of nanotechnologies for cellular electrophysiology are examined, as well as the most recent developments in micro- and nano-devices for cancer diagnostics and therapy targeting bioelectricity.

Molecular dissection of a hyper-aggressive CBFB-MYH11/FLT3-ITD–positive acute myeloid leukemia

Acute Myeloid Leukaemia (AML) is a haematological malignancy showing a hypervariable landscape of clinical outcomes and phenotypic differences, explainable by heterogeneity at the cellular and molecular level. Among the most common genomic alterations, CBFB-MYH11 rearrangement and FLT3-ITD gene mutations, have opposite clinical significance and are unfrequently associated. We present here a Molecular Case Report in which these two events co-exist an ultra-aggressive phenotype resulting in death in 4 days from hospital admittance. Somatic and germline Whole Exome Sequencing analysis was performed to uncover other putative driver mutations, de-novo genomic structural events or germline clusters increasing cancer insurgence. Only three mutations in LTK, BCAS2 and LGAS9 were found, unlikely causative of the exhibited phenotype, prompting to additional investigation of the rare CBFB-MYH11/ FLT3-ITD scenario.

The role of fetal programming in human carcinogenesis - May the Barker hypothesis explain interindividual variability in susceptibility to cancer insurgence and progression?

The growing incidence of cancers is pushing oncologists to find out new explanations other than the somatic mutation theory, based on the accumulation of DNA mutations. In particular, the embryo-fetal exposure to an increasing number of environmental factors during gestation might represent a trigger able to influence the susceptibility of the newborn to develop cancer later in life. This idea agrees with the fetal programming theory, also known as the Barker hypothesis. Here the role of insulin-like growth factors, thymosin beta-4, and epigenome are discussed as mediators of cancer in prenatal human development. The role of epigenetic factors that during gestation increase the predisposition to develop cancer and the similarities in the gene expression (like MMP9, OPN, TP53 and CDKN2A) between embryonic development and cancer are key factors. Likewise, maternal obesity might be able to re-program embryo-fetal development with long-term changes, including an increased risk to develop neuroblastoma and acute leukemia. Birth weight alone and birth weight corrected for gestational age are proposed as important variables capable of predicting the vulnerability to develop cancers. According to the findings here reported, we hypothesize that cancer prevention should start during gestation by improving the quality of maternal diet. In conclusion, the Barker hypothesis should be applied to cancer as well. Therefore, the identification of the epigenetic factors of cancer appears mandatory, so that the cancer prevention might start in the womb before birth.

Another Look at Dietary Polyphenols: Challenges in Cancer Prevention and Treatment.

Cancer is a pathology that impacts in a profound manner all over the world. The election strategy against cancer often uses chemotherapy and radiotherapy, which, more often than not, can present many side effects and are not always considered reliable efficacy. By contrast, it is widely known that a diet rich in fruit and vegetables has a protective effect against cancer insurgence and development. Polyphenols are generally believed to be responsible for those beneficial actions, at least partially. In this review, we highlight the metabolic interaction between polyphenols and our metabolism and discuss their potential for anticancer prevention and therapy.

From Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immune Response to Cancer Onset via Molecular Mimicry and Cross-Reactivity.

Background and Objectives Whether exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may predispose to the risk of cancer in individuals with no prior cancers is a crucial question that remains unclear. To confirm/refute possible relationships between exposure to the virus and ex novo insurgence of tumors, this study analyzed molecular mimicry and the related cross-reactive potential between SARS-CoV-2 spike glycoprotein (gp) antigen and human tumor-suppressor proteins. Materials and Methods Tumor-associated proteins were retrieved from UniProt database and analyzed for pentapeptide sharing with SARS-CoV-2 spike gp by using publicly available databases. Results An impressively high level of molecular mimicry exists between SARS-CoV-2 spike gp and tumor-associated proteins. Numerically, 294 tumor-suppressor proteins share 308 pentapeptides with the viral antigen. Crucially, the shared peptides have a relevant immunologic potential by repeatedly occurring in experimentally validated epitopes. Such immunologic potential is of further relevancy in that most of the shared peptides are also present in infectious pathogens to which, in general, human population has already been exposed, thus indicating the possibility of immunologic imprint phenomena. Conclusion This article described a vast peptide overlap between SARS-CoV-2 spike gp and tumor-suppressor proteins, and supports autoimmune cross-reactivity as a potential mechanism underlying prospective cancer insurgence following exposure to SARS-CoV-2. Clinically, the findings call for close surveillance of tumor sequelae that possibly could result from the current coronavirus pandemic.

P2X7 Variants in Oncogenesis.

The P2X7 receptor for extracellular ATP is a well-established mediator of tumoral development and progression both in solid cancers and hematological malignancies. The human P2X7 gene is highly polymorphic, and several splice variants of the receptor have been identified in time. P2X7 single-nucleotide polymorphisms (SNPs) have been broadly analyzed by studies relating them to pathologies as different as infectious, inflammatory, nervous, and bone diseases, among which cancer is included. Moreover, in the last years, an increasing number of reports concentrated on P2X7 splice variants’ different roles and their implications in pathological conditions, including oncogenesis. Here, we give an overview of established and recent literature demonstrating a role for human P2X7 gene products in oncological conditions, mainly focusing on current data emerging on P2X7 isoform B and nfP2X7. We explored the role of these and other genetic variants of P2X7 in cancer insurgence, dissemination, and progression, as well as the effect of chemotherapy on isoforms expression. The described literature strongly suggests that P2X7 variants are potential new biomarkers and therapeutical targets in oncological conditions and that their study in carcinogenesis deserves to be further pursued.

Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach.

Alterations in DNA repair pathways are one of the main drivers of cancer insurgence. Nevertheless, cancer cells are more susceptible to DNA damage than normal cells and they rely on specific functional repair pathways to survive. Thanks to advances in genome sequencing, we now have a better idea of which genes are mutated in specific cancers and this prompted the development of inhibitors targeting DNA repair players involved in pathways essential for cancer cells survival. Currently, the pivotal concept is that combining the inhibition of mechanisms on which cancer cells viability depends is the most promising way to treat tumorigenesis. Numerous inhibitors have been developed and for many of them, efficacy has been demonstrated either alone or in combination with chemo or radiotherapy. In this review, we will analyze the principal pathways involved in cell cycle checkpoint and DNA repair focusing on how their alterations could predispose to cancer, then we will explore the inhibitors developed or in development specifically targeting different proteins involved in each pathway, underscoring the rationale behind their usage and how their combination and/or exploitation as adjuvants to classic therapies could help in patients clinical outcome.

Genotype-phenotype relations of the von Hippel-Lindau tumor suppressor inferred from a large-scale analysis of disease mutations and interactors.

Familiar cancers represent a privileged point of view for studying the complex cellular events inducing tumor transformation. Von Hippel-Lindau syndrome, a familiar predisposition to develop cancer is a clear example. Here, we present our efforts to decipher the role of von Hippel-Lindau tumor suppressor protein (pVHL) in cancer insurgence. We collected high quality information about both pVHL mutations and interactors to investigate the association between patient phenotypes, mutated protein surface and impaired interactions. Our data suggest that different phenotypes correlate with localized perturbations of the pVHL structure, with specific cell functions associated to different protein surfaces. We propose five different pVHL interfaces to be selectively involved in modulating proteins regulating gene expression, protein homeostasis as well as to address extracellular matrix (ECM) and ciliogenesis associated functions. These data were used to drive molecular docking of pVHL with its interactors and guide Petri net simulations of the most promising alterations. We predict that disruption of pVHL association with certain interactors can trigger tumor transformation, inducing metabolism imbalance and ECM remodeling. Collectively taken, our findings provide novel insights into VHL-associated tumorigenesis. This highly integrated in silico approach may help elucidate novel treatment paradigms for VHL disease.

Enigmatic Ladies of the Rings: How Cohesin Dysfunction Affects Myeloid Neoplasms Insurgence.

The genes of the cohesin complex exert different functions, ranging from the adhesion of sister chromatids during the cell cycle, DNA repair, gene expression and chromatin architecture remodeling. In recent years, the improvement of DNA sequencing technologies allows the identification of cohesin mutations in different tumors such as acute myeloid leukemia (AML), acute megakaryoblastic leukemia (AMKL), and myelodysplastic syndromes (MDS). However, the role of cohesin dysfunction in cancer insurgence remains elusive. In this regard, cells harboring cohesin mutations do not show any increase in aneuploidy that might explain their oncogenic activity, nor cohesin mutations are sufficient to induce myeloid neoplasms as they have to co-occur with other causative mutations such as NPM1, FLT3-ITD, and DNMT3A. Several works, also using animal models for cohesin haploinsufficiency, correlate cohesin activity with dysregulated expression of genes involved in myeloid development and differentiation. These evidences support the involvement of cohesin mutations in myeloid neoplasms.

Melatonin and Hippo Pathway: Is There Existing Cross-Talk?

Melatonin is an indolic hormone that regulates a plethora of functions ranging from the regulation of circadian rhythms and antioxidant properties to the induction and maintenance of tumor suppressor pathways. It binds to specific receptors as well as to some cytosolic proteins, leading to several cellular signaling cascades. Recently, the involvement of melatonin in cancer insurgence and progression has clearly been demonstrated. In this review, we will first describe the structure and functions of melatonin and its receptors, and then discuss both molecular and epidemiological evidence on melatonin anticancer effects. Finally, we will shed light on potential cross-talk between melatonin signaling and the Hippo signaling pathway, along with the possible implications for cancer therapy.

Chromatin Accessibility Studied by Slow Scan FCS in the Eukaryotic Nucleus

DNA is one of the most important biological macromolecules, since it harbors the genetic information of the cell. In order to fit in eukaryotic cell nucleus, DNA is highly compacted and packed by histones in chromatin. Chromatin compaction has recently been shown to be related to cell epigenetic states[1] and levels of commitment [2]. It seems also to be involved in important processes like senescence and cancer [3,4]: it could be interesting to study chromatin degree of compaction in relation to cancer insurgence and progression.Fluorescence Correlation Spectroscopy (FCS) is a technique able to probe chromatin accessibility in living cells by measuring fast diffusion of molecules like EGFP in the range between microseconds to milliseconds. Here, in order to quantify local chromatin accessibility, we sample several positions within the nucleus by performing a slow orbital scan. The slow scan allows us to ignore the motion of the scanner and analyze the data as in single point FCS without losing temporal resolution. To extract the diffusion properties in distinct sub-nuclear compartments, we sort the sampled points based on the intensity value measured in the same or in another channel (e.g. Hoechst 33342) prior to averaging. In this way we can rapidly compare, for instance, the diffusion properties inside heterochromatin and euchromatin. We discuss the advantages and limitations of the method, and its application for comparing chromatin accessibility in cellular models of different cancer stages.[1] Boettiger A. et al., Nature, 2016 Jan; 418-22[2] Ricci M. et al., Cell, 2015 Mar; 1145-58.[3] Di Micco R. et al., Nat Cell Biol, 2011 Mar; 292-302[4] Sulli G. et al., Nat Rev Cancer, 2012 Oct; 709-20[5] Dross N. et al., PLoS One. 2009; e5041.

Abstract 2367: Tumor-infiltrating (TINKs) and tumor-associated (TANKs) natural killer cells: a new player in the inflammatory orchestration of tumor angiogenesis in colon cancer

Abstract Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide and a prevailing cause of cancer-related mortality. Several factors increase the risk of developing the tumor, including age, inflammatory bowel disease, personal and/or family history of colorectal tumors (adenoma or adenocarcinoma), and environmental factors. In spite of the extensive evidence indicating a role for inflammation in both colon cancer insurgence and progression, there is relatively little information concerning the role of inflammatory cells in CRC progression. Natural Killer (NK) cells are effectors lymphocytes of innate immunity that can potentially control tumors by their cytotoxic activity. Several immune cells within the tumors, like macrophages, neutrophils, myeloid-derived suppressor (MSDCs) cells and dendritic cells (DCs) have been reported to acquire an altered phenotype that reflects attenuation of anti-tumor activity and enhancement of pro-tumor activities, including angiogenesis. We recently identified a peculiar NKs subset infiltrating Non Small Cell Lung Cancer (NSCLC), that we termed TINKs, described as CD56brightCD16- NKs, able to produce large amount of VEGF, PlGF and IL-8 and induce angiogenesis in vitro. We therefore extended our studies on CRC TINKs and TANKs. NK cell were isolated from blood and tissue (adjacent-normal/tumour) samples from patients with CRC then phenotipically and functionally characterized for surface antigen expression and cytokine profiling by multiparametric flow cytometry. Finally, functional studies were performed on human umbelical vein cells (HUVECs), using conditioned media (CM) derived from isolated NKs. We found that the CD56brightCD16- NK cells predominate in both the tumors and adjacent tissues derived from colo-rectal carcinoma (CRC) samples and that are able to release substantial amounts of pro-angiogenic factors, including VEGF, PlGF and IL-8, exert low cytotoxic activities and induce migration of and capillary-like structure formation of endothelial cells in vitro. When we look at the molecular mechanisms involved in TINK and TANK angigoenic switch, we fould out that TGFβ1, an abundant cytokine within the tumor microenvironent, strongly up-regulates VEGF and PlGF release by peripheral blood NK cells from healthy age-matched donors. Taken together, the “switched” phenotype and function of tumor infiltrating NK cells acquire a broad implications in the role of immune response against tumors, ranging from a deficient control of cancer to an altered crosstalk with other relevant players of both innate ad acquired immune response. This places NK cells as a new player in the inflammatory orchestration of tumor angiogenesis. Citation Format: Antonino Bruno, Barbara Bassani, Silvia Zanellato, Sara Canali, Lorenzo Dominioni, Luigi Boni, Cassinotti Elisa, Giulia David, Katiuscia Dallaglio, Lorenzo Mortara, Douglas M. Noonan, Adriana Albini. Tumor-infiltrating (TINKs) and tumor-associated (TANKs) natural killer cells: a new player in the inflammatory orchestration of tumor angiogenesis in colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2367. doi:10.1158/1538-7445.AM2015-2367

Nuclear DICKKOPF-1 as a biomarker of chemoresistance and poor clinical outcome in colorectal cancer.

Sporadic colorectal cancer (CRC) insurgence and progression depend on the activation of Wnt/β-catenin signaling. Dickkopf (DKK)-1 is an extracellular inhibitor of Wnt/β-catenin signaling that also has undefined β-catenin-independent actions. Here we report for the first time that a proportion of DKK-1 locates within the nucleus of healthy small intestine and colon mucosa, and of CRC cells at specific chromatin sites of active transcription. Moreover, we show that DKK-1 regulates several cancer-related genes including the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) and Ral-binding protein 1-associated Eps domain-containing 2 (REPS2), which are involved in detoxification of chemotherapeutic agents. Nuclear DKK-1 expression is lost along CRC progression; however, it remains high in a subset (15%) of CRC patients (n = 699) and associates with decreased progression-free survival (PFS) after chemotherapy administration and overall survival (OS) [adjusted HR, 1.65; 95% confidence interval (CI), 1.23-2.21; P = 0.002)]. Overexpression of ALDH1A1 and REPS2 associates with nuclear DKK-1 expression in tumors and correlates with decreased OS (P = 0.001 and 0.014) and PFS. In summary, our findings demonstrate a novel location of DKK-1 within the cell nucleus and support a role of nuclear DKK-1 as a predictive biomarker of chemoresistance in colorectal cancer.

Green Tea and Anticancer Perspectives: Updates from Last Decade

Green tea is the most widely consumed beverage besides water and has attained significant attention owing to health benefits against array of maladies, e.g., obesity, diabetes mellitus, cardiovascular disorders, and cancer insurgence. The major bioactive molecules are epigallocatechin-3-gallate, epicatechin, epicatechin-3-gallate, epigallocatechin, etc. The anticarcinogenic and antimutagenic activities of green tea were highlighted some years ago. Several cohort studies and controlled randomized trials suggested the inverse association of green tea consumption and cancer prevalence. Cell culture and animal studies depicted the mechanisms of green tea to control cancer insurgence, i.e., induction of apoptosis to control cell growth arrest, altered expression of cell-cycle regulatory proteins, activation of killer caspases, and suppression of nuclear factor kappa-B activation. It acts as carcinoma blocker by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation, and metastasis. However, results generated from some research interventions conducted in different groups like smokers and nonsmokers, etc. contradicted with aforementioned anticancer perspectives. In this review paper, anticancer perspectives of green tea and its components have been described. Recent findings and literature have been surfed and arguments are presented to clarify the ambiguities regarding anticancer perspectives of green tea and its component especially against colon, skin, lung, prostate, and breast cancer. The heading of discussion and future trends is limelight of the manuscript. The compiled manuscript provides new avenues for researchers to be explored in relation to green tea and its bioactive components.

Watermelon lycopene and allied health claims.

Presently, functional foods and nutraceuticals are gaining immense importance in the prevention of various maladies through dietary regimen module. Consumption of fruits and vegetables based diet has pursuit a range of bioactive components, especially phytochemicals targeting life threatening ailments. In this context, lycopene is an extensively studied antioxidant potentially present in watermelon, tomato, pink guava etc. Watermelon is one of the unique sources having readily available cis-isomeric lycopene. The distinctive aroma of watermelon is imparted by medium- and short-chain fatty acids along with geranial, ß-ionone and neral. Its consumption has been escalated owing to rich nutritional profile and allied health benefits. It is effective in reducing the extent of cancer insurgence, cardiovascular disorders, diabetes and macular diseases. The structural characteristics, physiochemical properties and therapeutic effects of lycopene are the limelight of the manuscript. However, further research investigations are still needed to address the health enhancing potential of watermelon lycopene.

WNT-pathway components as predictive markers useful for diagnosis, prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer

The key role of the Wnt/β-catenin signaling in colorectal cancer (CRC) insurgence and progression is now recognized and several therapeutic strategies targeting this pathway are currently in developing. Wnt/β-catenin signaling not only dominates the early stages of sporadic colorectal cancer (SCC), but could also represent the connection between inflammatory bowel diseases (IBD) and increased risk of developing SCC. The knowledge on the sequential molecular events of Wnt-signaling cascade in IBD and during colorectal carcinogenesis, might provide new diagnostic/prognostic markers and could be helpful for optimizing the treatment protocols, thus improving the efficacy of Wnt-targeting therapies. We performed a comparative evaluation of the expression of some crucial molecules participating to Wnt signaling in an animal model of chemically-induced CRC and in human tissues obtained from patients suffering from IBD or at sequential stages of SCC. Specifically, we analyzed upstream events of Wnt signaling including β-catenin nuclear translocation and loss of E-cadherin and APC functions, and downstream events including c-Myc and Cyclin-D1 expression. We demonstrated that these crucial components of the Wnt/β-catenin pathway, when evaluated by immunohistochemistry using a multiparametric approach that includes the analyses of both expression and localization, could be potent markers for diagnosis, prevention and therapy in IBD and SCC, also possessing a predictive value for responsiveness to Wnt-targeting therapies. Furthermore, we showed that the animal model of chemically-induced CRC mimics the molecular events of Wnt signaling during IBD and SCC development in humans and may therefore be suitable for testing chemopreventive or therapeutic drugs targeting this pathway.

Immunity: Plants as Effective Mediators

In the domain of nutrition, exploring the diet–health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.

Aqueous Garlic Extract; Natural Remedy to Improve Haematological, Renal and Liver Status

Functional foods are gaining popularity worldwide owing to the consumer’s preference towards the consumption of natural and safe products in dietary modifications. Garlic (Allium sativum L., Liliaceae.) is an essential vegetable that have been widely utilized as seasoning, flavouring, culinary and in herbal remedies. Garlic is well known to acquire an array of phytochemicals. These bioactive molecules are playing pivotal role in maintaining human health and having potential to reduce various ailments like diabetes, cholesterol, cardiovascular diseases and cancer insurgence. Considering the aim, in vivo study was conducted using New Zeeland type rabbits, providing aqueous garlic extract for a period of 28 days. Accordingly, four groups (G0, G1, G2 and G3) were designed and provide different doses of extract (control, 3, 6 and 9 mL/kg b.w). Functional garlic extract containing water soluble active components resulted in significant reduction in RBC (6.94 ± 0.47 (106/mm3 in G2) while WBC improve (16.97 ± 1.70) in G2. Haemoglobin and haematocrit, packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration were also modulated well in G2 as compare to other groups. Regarding the total protein, maximum was recorded (7.23 ± 0.58) in G2 while lowest was (6.72 ± 0.15g/L) in G0. Albumin, globulin and electrolytes like Sodium (Na) and potassium (K) exhibited significant difference by using different concentration of aqueous garlic extract. Moreover, liver functioning test, urea, creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) also showed significant modulation using the aqueous garlic extract.From the present investigation, it is deduced that garlic preparations like aqueous extract is effective against various maladies because of its functional and nutraceutical aspects.

Aqueous garlic extract attenuates hypercholesterolemic and hyperglycemic perspectives; rabbit experimental modeling

Functional and nutraceutical foods are gaining popularity worldwide due to the consumer trend towards natural cure by means of dietary modifications. In 20th Century, nutritionists of the Western world focused mainly on the identification, isolation and purification of nutrients essential for human growth and development. Garlic (Allium sativum), is one of the most essential vegetables providing health benefits due to array of bioactive compounds. These bioactive moieties are responsible for curing various lifestyle related disorders like hyperlipidemia, diabetes, obesity and cancer insurgence. In this context, aqueous garlic extraction was carried out followed by in vivo modeling. Efficacy study was conducted by providing aqueous garlic extract along with basal diet on rabbits for a period of 28 days. Accordingly, four groups were made providing different concentrations of aqueous garlic extract (control, 3, 6 and 9 mL/kg body weight). Functional garlic extract containing water soluble active compounds resulted in significant reduction in total cholesterol and LDL level indicating their effectiveness against hypercholesterolemic perspectives and allied discrepancies. Likewise, serum glucose level was also substantially reduced by aqueous garlic extract. From the present investigation, it was deduced that different concentrations of aqueous garlic extract were effective against hypercholesterolemia and hyperglycemia. Key words: Functional food, nutraceutical foods, aqueous garlic extract, hypercholesterolemia, hyperglycemic perspectives.

Selected Functional Foods for Potential in Disease Treatment and Their Regulatory Issues

The significant association between diet and human health broadens the consumer concept to look at food not only for its basic nutrition but also for allied health benefits. Nevertheless, a large segment of the population is still reluctant to buy functional foods due to ambiguities related to their health claims. This review highlighted the role of functional foods against various physiological threats, like cardiovascular disorders, diabetes, oxidative stress, cancer insurgence, and immune dysfunction. Recent developments in dietary supplements are also the limelight of the article. The discussion also encapsulated the role and responsibilities of regulatory agencies, such as the Food and Agriculture Organization, the Codex Alimentarius Commission, and the International Alliance of Dietary Food Supplement Association, in harmonizing the legislations regarding the risk assessment and health claims of functional foods.