Search Results (1,288)

Background: Protein hydrolysates from insects are recognized for their biological activities. Black soldier fly larvae (BSFL) have drawn attention due to their antioxidant protein hydrolysates. However, research on bioactive peptides derived from these hydrolysates, particularly their cancer chemopreventive potential, remains limited. This study aims to evaluate the antioxidant, anti-inflammatory, antimutagenic, and anticancer activities of BSFL-derived bioactive peptides and explore the molecular mechanisms. Methods: Alkali-soluble BSFL protein (ASBP) was extracted and hydrolyzed using Alcalase and bromelain under optimized conditions. Antioxidant activity was assessed via FRAP, ABTS, and DPPH assays. The hydrolysate with the highest antioxidant activity was fractionated into molecular weight (MW) groups (>30, 10, and <3 kDa). The bioactivity of fractionated peptides was evaluated through antioxidant, anti-inflammatory (nitric oxide production in RAW 264.7 cells), antimutagenic (Ames test), and anticancer (CCK-8 assay on HCT 116, COLO205, Cw-2, and Caco-2 cells) assays. Mechanistic insights were obtained via microarray and Western blot analyses. Peptides were identified by LC-MS/MS. Results: The ASBP-Alcalase hydrolysate (ASBP-AH) showed optimal antioxidant activity at 3% (w/w) for 4 h. The ASBP-AH 30 (MW > 30 kDa) fraction exhibited the highest antioxidant capacity. In contrast, the ASBP-AH3 (MW < 3 kDa) fraction exhibited significant antimutagenic effects, reduced nitric oxide production, and decreased COLO205 cell viability. Treatment with ASBP-AH3 at its LC₅₀ dose modulated the SKP2/p21/cyclin D1 pathways. Mostly peptides from ASBP-AH3 were composed of hydrophobic and charged amino acids. Conclusions: BSFL-derived bioactive peptides exhibit potential as multifunctional agents for cancer chemoprevention. In vivo studies are required to explore their clinical applications. Full article

Allyl isothiocyanate (AITC) is a low-molecular-weight natural chemical predominantly obtained from the autolysis of sinigrin, a glucosinolate found in cruciferous vegetables like mustard, horseradish, and wasabi. AITC has sparked widespread interest due to its various biological actions, which include strong antioxidant, anti-inflammatory, antibacterial, and anticancer capabilities. This compound offers promising potential in several fields, particularly in food preservation, medicine, and enhancing food quality through natural means. AITC’s effectiveness against a broad spectrum of microorganisms, including foodborne pathogens and spoilage agents, makes it an attractive natural alternative to synthetic preservatives. The potential to extend the shelf life of perishable foods makes AITC an important tool for food production, meeting rising customer demand for natural additives. In addition to its antimicrobial effects, AITC demonstrates significant anti-inflammatory activity, reducing levels of pro-inflammatory cytokines and modulating key signaling pathways, which could make it valuable in managing chronic inflammatory conditions. Furthermore, emerging research highlights its potential in cancer prevention and treatment, as AITC has been demonstrated to induce apoptosis and inhibit cell increase in several cancer cell lines, offering a natural approach to chemoprevention. This review delves into the chemical structure, metabolism, and bioavailability of freshly produced AITC, providing a comprehensive overview of its beneficial properties. Challenges related to AITC’s volatility, dosage optimization, and regulatory considerations are also discussed, alongside future research directions to enhance the stability and efficacy of AITC-based formulations. The findings underscore AITC’s role as a versatile bioactive compound with known potential to support human health and the sustainable food industry. Full article

The Qidong Liver Cancer Institute (QDLCI) and the Qidong Cancer Registry were established in 1972 with input from doctors, other medical practitioners, and non-medical investigators arriving from urban centers such as Shanghai and Nanjing. Medical teams were established to quantify the extent of primary liver cancer in Qidong, a corn-growing peninsula on the north side of the Yangtze River. High rates of liver cancer were documented and linked to several etiologic agents, including aflatoxins. Local corn, the primary dietary staple, was found to be consistently contaminated with high levels of aflatoxins, and bioassays using this corn established its carcinogenicity in ducks and rats. Observational studies noted a positive association between levels of aflatoxin in corn and incidence of liver cancer across townships. Biomarker studies measuring aflatoxin B₁ and its metabolite aflatoxin M₁ in biofluids reflected the exposures. Approaches to decontamination of corn from aflatoxins were also studied. In 1993, investigators from Johns Hopkins University were invited to visit the QDLCI to discuss chemoprevention studies in some townships. A series of placebo-controlled clinical trials were conducted using oltipraz (a repurposed drug), chlorophyllin (an over-the-counter drug), and beverages prepared from 3-day-old broccoli sprouts (rich in the precursor phytochemical for sulforaphane). Modulation of biomarkers of aflatoxin DNA and albumin adducts established proof of principle for the efficacy of these agents in enhancing aflatoxin detoxication. Serendipitously, by 2012, aflatoxin exposures quantified using biomarker measurements documented a many hundred-fold reduction. In turn, the Cancer Registry documents that the age-standardized incidence rate of liver cancer is now 75% lower than that seen in the 1970s. This reduction is seen in Qidongese who have never received the hepatitis B vaccination. Aflatoxin mitigation driven by economic changes switched the dietary staple of contaminated corn to rice coupled with subsequent dietary diversity leading to lower aflatoxin exposures. This 50-year effort to understand the etiology of liver cancer in Qidong provides the strongest evidence for aflatoxin mitigation as a public health strategy for reducing liver cancer burden in exposed, high-risk populations. Also highlighted are the challenges and successes of international team science to solve pressing public health issues. Full article

Nicotinamide (NAM), the amide form of vitamin B3, is a precursor to essential cofactors nicotinamide adenine dinucleotide (NAD⁺) and NADPH. NAD⁺ is integral to numerous cellular processes, including metabolism regulation, ATP production, mitochondrial respiration, reactive oxygen species (ROS) management, DNA repair, cellular senescence, and aging. NAM supplementation has demonstrated efficacy in restoring cellular energy, repairing DNA damage, and inhibiting inflammation by suppressing pro-inflammatory cytokines release. Due to its natural presence in a variety of foods and its excellent safety profile—even at high doses of up to 3 g/day—NAM is extensively used in the chemoprevention of non-melanoma skin cancers and the treatment of dermatological conditions such as blistering diseases, atopic dermatitis, rosacea, and acne vulgaris. Recently, its anti-aging properties have elevated NAM’s prominence in skincare formulations. Beyond DNA repair and energy replenishment, NAM significantly impacts oxidative stress reduction, cell cycle regulation, and apoptosis modulation. Despite these multifaceted benefits, the comprehensive molecular mechanisms underlying NAM’s actions remain not fully elucidated. This review consolidates recent research to shed light on these mechanisms, emphasizing the critical role of NAM in cellular health and its therapeutic potential. By enhancing our understanding, this work underscores the importance of continued exploration into NAM’s applications, aiming to inform future clinical practices and skincare innovations. Full article

Background and aims: Ginsenoside compound K (CK), a saponin metabolite of ginseng, exerts anticancer effects; however, its molecular mechanisms of action in lung cancer remain unclear. We investigated the involvement of silent information regulator 6 (SIRT6) and poly (ADP-ribose) polymerase 1 (PARP-1) in the anticancer effects of CK in lung cancer. Methods and Results: CK induced PARP-1 activation-mediated parthanatos via sequestosome-1/p62-mediated SIRT6 degradation and inhibited the proliferation of H460 cells. Although CK reduced procaspase-8 levels, no significant apoptotic cleavage of procaspase-3 or PARP-1 was observed. Furthermore, CK upregulated p27, p21, phospho-p53, and gamma-H2AX levels. CK increased LC3-II levels in a p62-independent manner, but p62 was upregulated by autophagy inhibition, indicating that p62 is involved in CK-induced autophagy. CK-treated cells showed typical features of parthanatos, including PARP-1 hyperactivation, intracellular redistribution of poly ADP-ribose and pro-apoptotic factors, and chromatin fragmentation. SIRT6 was degraded in a CK concentration- and time-dependent manner. SIRT6 protein was upregulated by PARP-1 inhibition, nicotinamide adenine dinucleotide (NAD)+ supplementation, antioxidants, and p62 knockdown, but was decreased by autophagy blockade. PARP-1 activation was negatively correlated with SIRT6 levels, indicating that SIRT6 and PARP-1 activation play complementary roles in CK-induced growth inhibition. Immunofluorescence staining, fractionation studies, and immunoprecipitation were used to confirm the colocalization and interaction between p62 and SIRT6. Conclusions: PARP-1 activation is promoted by p62-mediated SIRT6 degradation, which plays an important role in CK-induced growth inhibition. Therefore, SIRT6 is a potential biomarker for the chemopreventive effect of CK in lung cancer cells, but further studies on SIRT6 are needed for the clinical application of CK. Full article

Scientific research on stilbenes is conducted for their chemopreventive and therapeutic properties. In experimental studies, natural and synthetic trans-stilbenes exhibit antioxidant, anti-inflammatory, cardioprotective, and anticancer effects. The antitumor activity of some natural and synthetic stilbenes is associated with their interaction with cytochrome P450 family 1, which leads to the inhibition of procarcinogen activation. In the present study, three-dimensional quantitative structure–activity relationship analysis (3D-QSAR) was performed on a series of forty-one trans-stilbene derivatives to identify the most significant features of the molecules responsible for their CYP1B1 inhibitory activity. The developed 3D-QSAR model presented a cross-validated correlation coefficient Q² of 0.554. The model’s predictive ability was confirmed by external validation (r² = 0.808). The information provided by 3D-QSAR analysis is expected to be valuable for the rational design of novel CYP1B1 inhibitors. Full article

(1) Background: Advances in food processing practices and health care are some of the most significant advances in modern daily life. The goal of this study is to evaluate the safety of potassium and sodium nitrates and nitrites when they are used as fertilizers in agriculture and food additives, as well as the known conversion of nitrate to nitrite in humans. (2) Methods: Various bioassays were conducted to investigate the effects of nitrates and nitrites in the Drosophila melanogaster genetic tester system. These assays focused on the modulation of degenerative processes at the molecular, cellular, individual, and population levels. Additionally, we assessed the chemopreventive potential and the ability to induce DNA strand breaks in HL-60 tumour cells. (3) Results: All nitrate and nitrite concentrations tested were shown to not be toxic or genotoxic in Drosophila since none of the compounds reached the LD₅₀ and significant genetic mutation. A positive or null protective capacity against a toxic agent was found for nitrates, not for nitrites, showing that sodium nitrite has a synergistic effect when combined with the oxidant toxin hydrogen peroxide; and a nutraceutical potential in the lifespan only for sodium nitrate to improve the quality of life in 5 days at ADI concentration. The in vitro results in human leukemia cells showed a chemopreventive potential only for potassium nitrate and sodium nitrite due to reducing the viability of HL-60 cells growth to 18% and 29%, respectively, compared to the controls at ADI (acceptable daily intake) concentrations. However, neither of these showed DNA damage or methylation modifications. (4) Conclusions: The tested compounds were shown to be safe to use during in vivo and in vitro tests when used at the extrapolated ADI concentrations. Full article

While a balanced diet can fulfill most nutritional needs, optimizing the composition of specific foods like broccoli can amplify their health benefits. Background/Objectives: Broccoli (Brassica oleracea L. Italica group) is a widely consumed cruciferous vegetable valued for its gastrointestinal and immune health benefits. However, the individual contributions and interactions of broccoli glucosinolates, as they hydrolyze into bioactive isothiocyanates, remain poorly understood. Methods: This study investigated mixtures of four major aliphatic glucosinolates—glucoraphanin, gluconapin, progoitrin, and sinigrin—in individual and combinational models to assess their effects on human colorectal cell proliferation. Results: Combination index analysis revealed moderate to strong antagonistic interactions among these glucosinolates, with the most significant antagonism observed during enzymatic hydrolysis by myrosinase. Mixture analysis identified an optimal glucosinolate ratio including glucoraphanin (81–84%), gluconapin (9–19%), and others (0–7%) to maximize their antiproliferative effects (adjusted R² > 0.80). This optimal profile was achievable within the target broccoli mapping population. Testing the near-optimal VB067 isogenic broccoli line showed a 44% increase in antiproliferative activity compared to the initial breeding parent or an average sister line. Conclusions: This study highlights the potential of leveraging nutrient–nutrient interactions to guide molecular breeding and produce functional varieties of cruciferous vegetables with optimized health benefits. Full article

Colorectal cancer (CRC) is one of the major reasons for cancer-related deaths around the world. Constitutive activation of WNT pathway, due to APC gene mutation, is the characteristic feature of most human colon tumors. Familial adenomatous polyposis (FAP) patients inherit APC mutations and pose an absolute risk of developing CRC in their lifetime. The genetically modified APC mouse models have paved the way to study various aspects of the hereditary human CRC, including biochemical, molecular, and histological aspects. Preclinical and clinical data suggest that certain dietary supplements, NSAIDs, natural products, and chemically synthesized compounds, can help in intercepting CRC incidence and progression by modulating various hallmarks of cancer. In this review, we have provided a summary of promising natural and synthetic agents that demonstrated chemopreventive efficacy against CRC in the FAP-mimicking APC^Min/+ mouse model. Full article

Olive oil and table olives are considered staples of the Mediterranean diet and have been associated with various health benefits. Literature reports that the final composition of the olive drupe is greatly affected by varietal and agronomic factors, each contributing to a different degree. To that end, the objective of the study was the evaluation of the contribution of different agronomic conditions applied to two Greek olive varieties (Koroneiki, Mastoidis) using a holistic approach of in vitro methods. The findings highlight the importance of the application of a combination of agronomic techniques for each variety, as marked by the differences found in the antioxidant radical-scavenging and reducing power assays. Furthermore, the results obtained from the measurement of redox biomarkers (GSH, ROS, TBARS) in cell lines (EA.hy926, HepG2, MKN45) treated with olive samples demonstrate the capacity of the samples to induce redox imbalance, either by protecting normal cells from damage, or by inducing oxidative damage in cancer cell lines, with the Athinolia samples exhibiting greater antioxidant potential at lower concentrations. This particular finding could have further applications in possible chemo-preventive approaches facilitated by antioxidant compounds of natural origins. Full article

Women carrying pathogenic/likely pathogenic (P/LP) variants in moderate- or high-penetrance genes have an increased risk of developing breast cancer. However, most P/LP variants associated with breast cancer risk show incomplete penetrance. Age, gender, family history, polygenic risk, lifestyle, reproductive, hormonal, and environmental factors can affect the expressivity and penetrance of the disease. However, there are gaps in translating how individual genomic variation affects phenotypic presentation. The expansion of criteria for genetic testing and the increasing utilization of comprehensive genetic panels may enhance the identification of individuals carrying P/LP variants linked to hereditary breast cancer. Individualized risk assessment could facilitate the implementation of personalized risk-reduction strategies for these individuals. Preventive interventions encompass lifestyle modifications, chemoprevention, enhanced surveillance through breast imaging, and risk-reducing surgeries. This review addresses the current literature’s inconsistencies and limitations, particularly regarding risk factors and the intensity of preventive strategies for women with P/LP variants in moderate- and high-penetrance genes. In addition, it synthesizes the latest evidence on risk assessment and primary and secondary prevention in women at high risk of breast cancer. Full article

Background: Inflammatory bowel diseases (IBDs) have been associated with a higher risk of colorectal cancer (CRC) development and chronic colonic inflammation seems to have a critical role in the pathogenesis of CRC in patients suffering from IBD. In respect to that, surveillance colonoscopy at regular intervals is recommended in patients with colitis. Objective: This review aims to explore the chemopreventive potential of a range of agents, including mesalazine, thiopurines, anti-TNF agents, statins, ursodeoxycholic acid, aspirin, folic acid, and nutraceuticals. Results: These agents target inflammation, oxidative stress, and oncogenic pathways, thereby offering the potential to reduce the risk of CRC in patients with IBD. Anti-TNF agents, such as infliximab and adalimumab, not only reduce colonic inflammation, but also play a protective role against CRC by lessening the carcinogenic effects associated with prolonged inflammatory processes. Furthermore, mesalazine and thiopurines have demonstrated established efficacy, while newer biologics, including interleukin inhibitors, show promising advancements. Although nutraceuticals and dietary interventions require further clinical validation, they offer additional possibilities for non-pharmacological prevention. Conclusion: Despite progress, knowledge gaps persist regarding the long-term safety, optimal dosing, and combined use of these agents. A significant reduction in the incidence of CRC in patients with IBD could be achieved by advancing chemoprevention and personalizing strategies. Full article

Dirofilaria immitis and Angiostrongylus vasorum are major parasitic nematodes of dogs. Many environmental and phenological changes have recently modified their geographic patterns in many countries; thus, this study has updated the distribution of D. immitis and A. vasorum in dog populations of selected regions of Central and Southern Italy. Also, collateral data on other endoparasites affecting the study population have been collected. Blood and fecal samples collected from 2000 dogs were tested using Knott’s test and copromicroscopy (i.e., Baermann’s and fecal flotation tests), respectively. Binomial logistic regression was performed to evaluate statistically significant associations between positivity for D. immitis and/or A. vasorum and potential risk factors. Overall, 35 (1.7%) and 62 (3.1%) dogs were positive for microfilariae of D. immitis and first stage larvae (L1) of A. vasorum, respectively, while 3 (0.1%) were co-infected by both nematodes. Microfilariae of Dirofilaria repens were found in 148 (7.4%) dogs, while at the flotation, eggs of Ancylostomatidae, Trichuris vulpis, and ascarids were found in the feces of 323 (16.5%), 249 (12.4%), and 172 (8.6%), dogs, respectively. Overall, 217 (10.8%) and 44 (2.2%) dogs were positive for eggs of Capillaria aerophila and Capillaria boehmi. The presence of cardiorespiratory clinical signs or non-specific signs, history of travel, and an age of >4 years old were significantly associated with positivity for D. immitis, while A. vasorum was significantly recorded in dogs with cardiorespiratory signs, or with a history of mollusk ingestion or permanent outdoor housing. These results confirm that D. immitis is enzootic in the investigated regions of Central and Southern Italy, even where it was rare/undetected until recently. Indeed, although some dogs positive for D. immitis had a history of travel in enzootic areas, the majority of them were never moved, indicating that they acquired the parasite in the region where they live. Additionally, A. vasorum is stably enzootic in the study areas, as also are other extraintestinal nematodes (i.e., D. repens and C. aerophila) that are more frequently detected today than in the past. A high level of vigilance and routine parasitological screening are necessary, considering the high prevalence of intestinal parasites in owned dogs that are also co-infected by respiratory parasites. The implementation of chemoprevention against D. immitis in dogs living in the examined area should be encouraged. Full article

It has been known since the early days of the discovery of aflatoxin B1 (AFB1) that there were large species differences in susceptibility to AFB1. It was also evident early on that AFB1 itself was not toxic but required bioactivation to a reactive form. Over the past 60 years there have been thousands of studies to delineate the role of ~10 specific biotransformation pathways of AFB1, both phase I (oxidation, reduction) and phase II (hydrolysis, conjugation, secondary oxidations, and reductions of phase I metabolites). This review provides a historical context and substantive analysis of each of these pathways as contributors to species differences in AFB1 hepatoxicity and carcinogenicity. Since the discovery of AFB1 as the toxic contaminant in groundnut meal that led to Turkey X diseases in 1960, there have been over 15,000 publications related to aflatoxins, of which nearly 8000 have addressed the significance of biotransformation (metabolism, in the older literature) of AFB1. While it is impossible to give justice to all of these studies, this review provides a historical perspective on the major discoveries related to species differences in the biotransformation of AFB1 and sets the stage for discussion of other papers in this Special Issue of the important role that AFB1 metabolites have played as biomarkers of exposure and effect in thousands of human studies on the toxic effects of aflatoxins. Dr. John Groopman has played a leading role in every step of the way—from initial laboratory studies on specific AFB1 metabolites to the application of molecular biomarkers in epidemiological studies associating dietary AFB1 exposure with liver cancer, and the design and conduct of chemoprevention clinical trials to reduce cancer risk from unavoidable aflatoxin exposures by alteration of specific AFB1 biotransformation pathways. This article is written in honor of Dr. Groopman’s many contributions in this area. Full article