Exosomal Dynamics and Brain Redox Imbalance: Implications in Alzheimer's Disease Pathology and Diagnosis.

Oxidative burden plays a central role in Alzheimer's disease (AD) pathology, fostering protein aggregation, inflammation, mitochondrial impairment, and cellular dysfunction that collectively lead to neuronal injury. The role of exosomes in propagating the pathology of neurodegenerative diseases including AD is now well established. However, recent studies have also shown that exosomes are crucial responders to oxidative stress in different tissues. Thus, this offers new insights and mechanistic links within the complex pathogenesis of AD through the involvement of oxidative stress and exosomes. Several studies have indicated that exosomes, acting as intracellular communicators, disseminate oxidatively modified contents from one cell to another, propagating the pathology of AD. Another emerging aspect is the exosome-mediated inhibition of ferroptosis in multiple tissues under different conditions which may have a role in neurodegenerative diseases as well. Apart from their involvement in the pathogenesis of AD, exosomes enter the bloodstream serving as novel noninvasive biomarkers for AD; some of the exosome contents also reflect the cerebral oxidative stress in this disease condition. This review highlights the intricate interplay between oxidative stress and exosome dynamics and underscores the potential of exosomes as a novel tool in AD diagnosis.

Unveiling the dynamic relationship of viruses and/or symbiotic bacteria with plant resilience in abiotic stress.

In the ecosphere, plants interact with environmental biotic and abiotic partners, where unbalanced interactions can induce unfavourable stress conditions. Abiotic factors (temperature, water, and salt) are primarily required for plants healthy survival, and any change in their availability is reflected as a stress signal. In certain cases, the presence of infectious pathogens such as viruses, bacteria, fungi, protozoa, nematodes, and insects can also create stress conditions in plants, leading to the emergence of disease or deficiency symptoms. While these symptoms are often typical of abiotic or biotic stress, however, there are instances where they can intensify under specific conditions. Here, we primarily summarize the viral interactions with plants during abiotic stress to understand how these associations are linked together during viral pathogenesis. Secondly, focus is given to the beneficial effects of root-associated symbiotic bacteria in fulfilling the basic needs of plants during normal as well as abiotic stress conditions. The modulations of plant functional proteins, and their occurrence/cross-talk, with pathogen (virus) and symbiont (bacteria) molecules are also discussed. Furthermore, we have highlighted the biochemical and systematic adaptations that develop in plants due to bacterial symbiosis to encounter stress hallmarks. Lastly, directions are provided towards exploring potential rhizospheric bacteria to maintain plant-microbes ecosystem and manage abiotic stress in plants to achieve better trait health in the horticulture crops.

Polymer-mediated nanoformulations: a promising strategy for cancer immunotherapy.

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

Chitosan-PEI passivated carbon dots for plasmid DNA and miRNA-153 delivery in cancer cells.

These days carbon dots have been developed for multiple biomedical applications. In the current study, the transfection potential of synthesized carbon dots from single biopolymers such as chitosan, PEI-2kDa, and PEI-25kDa (CS-CDs, PEI2-CDs, and PEI25-CDs) and by combining two biopolymers (CP2-CDs and CP25-CDs) through a bottom-up approach have been investigated. The characterization studies revealed successful synthesis of fluorescent, positively charged carbon dots <20 nm in size. Synthesized carbon dots formed a stable complex with plasmid DNA (EGFP-N1) and miRNA-153 that protected DNA/miRNA from serum-induced degradation. In-vitro cytotoxicity analysis revealed minimal cytotoxicity in cancer cell lines (A549 and MDA-MB-231). In-vitro transfection of EGFP-N1 plasmid DNA with PEI2-CDs, PEI25-CDs and CP25-CDs demonstrated that these CDs could strongly transfect A549 and MDA-MB-231 cells. The highest EGFP-N1 plasmid transfection efficiency was observed with PEI2-CDs at a weight ratio of 32:1. PEI25-CDs polyplex showed maximum transfection at a weight ratio of 8:1 in A549 at a weight ratio of 16:1 in MDA-MB-231 cells. CP25-CDs exhibited the highest transfection at a weight ratio of 16:1 in both cell lines. The in-vitro transfection of target miRNA, i.e., miR-153 in A549 and MDA-MB-231 cells with PEI2-CDs, PEI25-CDs, and CP25-CDs suggested successful transfer of miR-153 into cells which induced significant cell death in both cell lines. Importantly, CS-CDs and CP2-CDs could be tolerated by cells up to 200 µg/mL concentration, while PEI2-CDs, PEI25-CDs, and CP25-CDs showed non-cytotoxic behavior at low concentrations (25 µg/mL). Together, these results suggest that a combination of carbon dots synthesized from chitosan and PEI (CP25-CDs) could be a novel vector for transfection nucleic acids that can be utilized in cancer therapy.

Sustainable Nanoparticles from Stephania glabra and Analysis of Their Anticancer Potential on 2D and 3D Models of Prostate Cancer.

In pursuit of a novel effective treatment for prostate cancer, methanolic extract of Stephania glabra tubers (Sg-ME) was utilized to fabricate silver (Sg-AgNP), copper oxide (Sg-CuONP), and silver-copper bimetallic nanoparticles (Sg-BNP). The characterization of the nanoparticles confirmed spherical shape with average diameters of 30.72, 32.19, and 25.59 nm of Sg-AgNP, Sg-CuONP, and Sg-BNP, respectively. Interestingly, these nanoparticles exhibited significant cytotoxicity toward the prostate cancer (PC3) cell line while being non-toxic toward normal cells. The nanoparticles were capable of inducing apoptosis in PC3 cells by enhancing reactive oxygen species (ROS) generation and mitochondrial depolarization. Furthermore, the shrinkage of 3D prostate tumor spheroids was observed after 4 days of treatment with these green nanoparticles. The 3D model system was less susceptible to nanoparticles as compared to the 2D model system. Sg-BNP showed the highest anticancer potential on 2D and 3D prostate cancer models.

Exosomal miRNAs as Next-generation Therapy Vehicles in Breast Cancer.

The second most pervasive cancer affecting the survival of women across the world is breast cancer. One of the biggest challenges in breast cancer treatment is the chemoresistance of cancer cells to various medications after some time. Therefore, highly specific blood-based biomarkers are required for early breast cancer diagnosis to overcome chemoresistance and improve patient survival. These days, exosomal miRNAs have attracted much attention as early diagnostic blood-based biomarkers because of their high stability, secretion from malignant tumor cells, and excellent specificity for different breast cancer subtypes. In addition, exosomal miRNAs regulate cell proliferation, invasion, metastasis, and apoptosis by binding to the 3'UTR of their target genes and limiting their production. This review focuses on the functions of exosomal miRNAs in tumorigenesis via targeting multiple signaling pathways as well as chemosensitivity and resistance mechanisms. In addition, the growing pieces of evidence discussed in this review suggest that circulating exosomal miRNAs could be utilized as potential next-generation therapeutic target vehicles in the treatment of breast cancer.

Nanoformulations of quercetin for controlled delivery: a review of preclinical anticancer studies.

One of the well-studied older molecules, quercetin, is found in large quantities in many fruits and vegetables. Natural anti-oxidant quercetin has demonstrated numerous pharmacological properties in preclinical and clinical research, including anti-inflammatory and anti-cancer effects. Due to its ability to control cell signaling pathways, including NF-κB, p53, activated protein-1 (AP-1), STAT3, and epidermal growth response-1 (Egr-1), which is essential in the initiation and proliferation of cancer, it has gained a lot of fame as an anticancer molecule. Recent research suggests that using nanoformulations can help quercetin to overcome its hydrophobicity while also enhancing its stability and cellular bioavailability both in vitro and in vivo. The main aim of this review is to focus on the comprehensive insights of several nanoformulations, including liposomes, nano gels, micelles, solid lipid nanoparticles (SLN), polymer nanoparticles, gold nanoparticles, and cyclodextrin complexes, to transport quercetin for application in cancer.

Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances.

Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy.

Potential of novel dual Z-scheme carbon quantum dots decorated MnIn2S4/CdS/Bi2S3 heterojunction for environmental applications.

In this work, CQDs decorated MnIn2S4/CdS/Bi2S3 heterojunction was prepared successfully by hydrothermal technique for photocatalytic disinfection of Escherichia coli (E. coli) and mineralization of methyl orange (MO) dye. The charge transferal route and mineralization process in CQDs-MnIn2S4/CdS/Bi2S3 heterojunction were comprehensively investigated by advanced spectroscopic techniques. The improved visible-light activity and enhanced photo-generated charge transferal efficacy caused dual Z-scheme CQDs-MnIn2S4/CdS/Bi2S3 heterojunction to achieve boosted photodegradation ability. The catalytic degradation trend was followed as CQDs-MnIn2S4/CdS/Bi2S3 > MnIn2S4 > CdS > Bi2S3. The dye was mineralized within 180 min under visible light irradiation. The effect of reaction parameters, pH effect, catalyst dosage, and H2O2 addition on MO degradation was also investigated. The degradation rate was maximal at pH 4 with a pseudo-first-order rate constant, 0.0438 min-1. The assessment of antibacterial properties revealed that CQDs-MnIn2S4/CdS/Bi2S3 composite effectively inactivated E. coli under visible light. Scavenging experiments, transient photocurrent response, and electron spin resonance spectroscopy suggested that •[Formula: see text] and holes were the dominant reactive species. The Z-scheme heterojunction is recyclable up to ten photocatalytic cycles according to recycling experiments. This research indicates the importance of dual Z-scheme CQDs decorated MnIn2S4/CdS/Bi2S3 heterojunction in wastewater remediation.

Novel Biocompatible Green Silver Nanoparticles Efficiently Eliminates Multidrug Resistant Nosocomial Pathogens and Mycobacterium Species.

Bacterial infection is a major crisis of 21st era and the emergence of multidrug resistant (MDR) pathogens cause significant health problems. We developed, green chemistry-based silver nanoparticles (G-Ag NPs) using Citrus pseudolimon fruit peel extract. G-Ag NPs has a spherical shape in the range of ~ 40 nm with a surface charge of - 31 Mv. This nano-bioagent is an eco-friendly tool to combat menace of MDR. Biochemical tests prove that G-Ag NPs are compatible with human red blood cells and peripheral blood mononuclear cells. There have been many reports on the synthesis of silver nanoparticles, but this study suggests a green technique for making non-cytotoxic, non-hemolytic organometallic silver nanoparticles with a high therapeutic index for possible use in the medical field. On the same line, G-Ag NPs are very effective against Mycobacterium sp. and MDR strains including Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, and Acinetobacter baumannii isolated from patient samples. Based on it, we filed a patent to Indian Patent Office (reference no. 202111048797) which can revolutionize the prevention of biomedical device borne infections in hospital pre/post-operated cases. This work could be further explored in future by in vivo experimentation with mice model to direct its possible clinical utility. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01061-0.

Aberrant protein glycosylation: Implications on diagnosis and Immunotherapy.

Glycosylation-mediated post-translational modification is critical for regulating many fundamental processes like cell division, differentiation, immune response, and cell-to-cell interaction. Alterations in the N-linked or O-linked glycosylation pattern of regulatory proteins like transcription factors or cellular receptors lead to many diseases, including cancer. These alterations give rise to micro- and macro-heterogeneity in tumor cells. Here, we review the role of O- and N-linked glycosylation and its regulatory function in autoimmunity and aberrant glycosylation in cancer. The change in cellular glycome could result from a change in the expression of glycosidases or glycosyltransferases like N-acetyl-glucosaminyl transferase V, FUT8, ST6Gal-I, DPAGT1, etc., impact the glycosylation of target proteins leading to transformation. Moreover, the mutations in glycogenes affect glycosylation patterns on immune cells leading to other related manifestations like pro- or anti-inflammatory effects. In recent years, understanding the glycome to cancer indicates that it can be utilized for both diagnosis/prognosis as well as immunotherapy. Studies involving mass spectrometry of proteome, site- and structure-specific glycoproteomics, or transcriptomics/genomics of patient samples and cancer models revealed the importance of glycosylation homeostasis in cancer biology. The development of emerging technologies, such as the lectin microarray, has facilitated research on the structure and function of glycans and glycosylation. Newly developed devices allow for high-throughput, high-speed, and precise research on aberrant glycosylation. This paper also discusses emerging technologies and clinical applications of glycosylation.

GLUT inhibitor WZB117 induces cytotoxicity with increased production of amyloid-beta peptide in SH-SY5Y cells preventable by beta-hydroxybutyrate: implications in Alzheimer's disease.

BACKGROUND: Inhibitors of glucose transporters are being explored as potential anti-cancer drugs. Decreased cerebral glucose utilization with reduced levels of several glucose transporters is also an important pathogenic signature of neurodegeneration of Alzheimer's disease, but its exact role in the pathogenesis of this disease is not established. We explored in an experimental model if inhibitors of glucose transporters could lead to altered amyloid-beta homeostasis, mitochondrial dysfunction, and neuronal death, which are relevant in the pathogenesis of Alzheimer's disease. METHODS: SH-SY5Y cells (human neuroblastoma cell line) were exposed to an inhibitor (WZB117) of several types of glucose transporters. We examined the effects of glucose hypometabolism on SH-SY5Y cells in terms of mitochondrial functions, production of reactive oxygen species, amyloid-beta homeostasis, and neural cell death. The effect of ß-hydroxybutyrate in ameliorating the effects of WZB117 on SH-SY5Y cells was also examined. RESULTS: We observed that exposure of SH-SY5Y cells to WZB117 caused mitochondrial dysfunction, increased production of reactive oxygen species, loss of cell viability, increased expression of BACE 1, and intracellular accumulation of amyloid ß peptide (Aß42). All the effects of WZB117 could be markedly prevented by co-treatment with ß-hydroxybutyrate. Cyclosporine A, a blocker of mitochondrial permeability transition pore (mPTP) activation, could not prevent cell death caused by WZB117. CONCLUSION: Results in this neuroblastoma model have implications for the pathogenesis of Alzheimer's disease and warrant further explorations of WZB117 in primary cultures of neurons and experimental animal models.

Biodegradable PEG-PCL Nanoparticles for Co-delivery of MUC1 Inhibitor and Doxorubicin for the Confinement of Triple-Negative Breast Cancer.

Combating triple-negative breast cancer (TNBC) is still a problem, despite the development of numerous drug delivery approaches. Mucin1 (MUC1), a glycoprotein linked to chemo-resistance and progressive malignancy, is unregulated in TNBC. GO-201, a MUC1 peptide inhibitor that impairs MUC1 activity, promotes necrotic cell death by binding to the MUC1-C unit. The current study deals with the synthesis and development of a novel nano-formulation (DM-PEG-PCL NPs) comprising of polyethylene glycol-polycaprolactone (PEG-PCL) polymer loaded with MUC1 inhibitor and an effective anticancer drug, doxorubicin (DOX). The DOX and MUC1 loaded nanoparticles were fully characterized, and their different physicochemical properties, viz. size, shape, surface charge, entrapment efficiencies, release behavior, etc., were determined. With IC50 values of 5.8 and 2.4 nm on breast cancer cell lines, accordingly, and a combination index (CI) of < 1.0, DM-PEG-PCL NPs displayed enhanced toxicity towards breast cancer cells (MCF-7 and MDA-MB-231) than DOX-PEG-PCL and MUC1i-PEG-PCL nanoparticles. Fluorescence microscopy analysis revealed DOX localization in the nucleus and MUC1 inhibitor in the mitochondria. Further, DM-PEG-PCL NPs treated breast cancer cells showed increased mitochondrial damage with enhancement in caspase-3 expression and reduction in Bcl-2 expression.In vivo evaluation using Ehrlich Ascites Carcinoma bearing mice explicitly stated that DM-PEG-PCL NPs therapy minimized tumor growth relative to control treatment. Further, acute toxicity studies did not reveal any adverse effects on organs and their functions, as no mortalities were observed. The current research reports for the first time the synergistic approach of combination entrapment of a clinical chemotherapeutic (DOX) and an anticancer peptide (MUC1 inhibitor) encased in a diblock PEG-PCL copolymer. Incorporating both DOX and MUC1 inhibitors in PEG-PCL NPs in the designed nanoformulation has provided chances and insights for treating triple-negative breast tumors. Our controlled delivery technology is biodegradable, non-toxic, and anti-multidrug-resistant. In addition, this tailored smart nanoformulation has been particularly effective in the therapy of triple-negative breast cancer. Supplementary Information: The online version contains supplementary material available at 10.1007/s10924-022-02654-4.

Immunotherapeutics in lung cancers: from mechanistic insight to clinical implications and synergistic perspectives.

BACKGROUND: Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. METHODS AND RESULTS: The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. CONCLUSIONS: In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.

Molecular mechanisms behind ROS regulation in cancer: A balancing act between augmented tumorigenesis and cell apoptosis.

ROS include hydroxyl radicals (HO.), superoxide (O2..), and hydrogen peroxide (H2O2). ROS are typically produced under physiological conditions and play crucial roles in living organisms. It is known that ROS, which are created spontaneously by cells through aerobic metabolism in mitochondria, can have either a beneficial or detrimental influence on biological systems. Moderate levels of ROS can cause oxidative damage to proteins, DNA and lipids, which can aid in the pathogenesis of many disorders, including cancer. However, excessive concentrations of ROS can initiate programmed cell death in cancer. Presently, a variety of chemotherapeutic drugs and herbal agents are being investigated to induce ROS-mediated cell death in cancer. Therefore, preserving ROS homeostasis is essential for ensuring normal cell development and survival. On account of a significant association of ROS levels at various concentrations with carcinogenesis in a number of malignancies, further studies are needed to determine the underlying molecular mechanisms and develop the possibilities for intervening in these processes.

Anticancer potential of oroxylin A: from mechanistic insight to synergistic perspectives.

Oroxylin A (OA), a well-known constituent of the root of Scutellariae plants, has been used in ethnomedicine already for centuries in treating various neoplastic disorders. However, only recent molecular studies have revealed the different mechanisms behind its action, demonstrating antiproliferative, anti-inflammatory, and proapoptotic effects, restricting also the spread of cancer cells to distant organs. A variety of cellular targets and modulated signal transduction pathways regulated by OA have been determined in diverse cells derived from different malignant tissues. In this review article, these anticancer activities are thoroughly described, representing OA as a potential lead structure for the design of novel more potent anticancer medicines. In addition, co-effects of this natural compound with conventional anticancer agents are analyzed and the advantages provided by nanotechnological methods for more efficient application of OA are discussed. In this way, OA might represent an excellent example of using ethnopharmacological knowledge for designing modern medicines.

The exploitation of enzyme-based cancer immunotherapy.

Cancer immunotherapy utilizes the immune system and its wide-ranging components to deliver anti-tumor responses. In immune escape mechanisms, tumor microenvironment-associated soluble factors and cell surface-bound molecules are mainly accountable for the dysfunctional activity of tumor-specific CD8+ T cells, natural killer (NK) cells, tumor associated macrophages (TAMs) and stromal cells. The myeloid-derived suppressor cells (MDSCs) and Foxp3+ regulatory T cells (Tregs), are also key tumor-promoting immune cells. These potent immunosuppressive networks avert tumor rejection at various stages, affecting immunotherapies' outcomes. Numerous clinical trials have elucidated that disruption of immunosuppression could be achieved via checkpoint inhibitors. Another approach utilizes enzymes that can restore the body's potential to counter cancer by triggering the immune system inhibited by the tumor microenvironment. These immunotherapeutic enzymes can catalyze an immunostimulatory signal and modulate the tumor microenvironment via effector molecules. Herein, we have discussed the immuno-metabolic roles of various enzymes like ATP-dephosphorylating ectoenzymes, inducible Nitric Oxide Synthase, phenylamine, tryptophan, and arginine catabolizing enzymes in cancer immunotherapy. Understanding the detailed molecular mechanisms of the enzymes involved in modulating the tumor microenvironment may help find new opportunities for cancer therapeutics.

The Colloquy between Microbiota and the Immune System in Colon Cancer: Repercussions on the Cancer Therapy.

Colorectal cancer is the second leading cause of cancer deaths worldwide and has engrossed researchers' attention toward its detection and prevention at early stages. Primarily associated with genetic and environmental risk factors, the disease has also shown its emergence due to dysbiosis in microbiota. The microbiota not only plays a role in modulating the metabolisms of metastatic tissue but also has a keen role in cancer therapy. The immune cells are responsible for secreting various chemokines and cytokines, and activating pattern recognition receptors by different microbes can lead to the trail by which these cells regulate cancer. Furthermore, mixed immune reactions involving NK cells, tumor-associated macrophages, and lymphocytes have shown their connection with the microbial counterpart of the disease. The microbes like Bacteroides fragilis, Fusobacterium nucleatum, and Enterococcus faecalis and their metabolites have engendered inflammatory reactions in the tumor microenvironment. Hence the interplay between immune cells and various microbes is utilized to study the changing metastasis stage. Targeting either immune cells or microbiota could not serve as a key to tackling this deadly disorder. However, harnessing their complementation towards the disease can be a powerful weapon for developing therapy and diagnostic/prognostic markers. In this review, we have discussed various immune reactions and microbiome interplay in CRC, intending to evaluate the effectiveness of chemotherapy and immunotherapy and their parallel relationship.

Gut Microbiota-Assisted Synthesis, Cellular Interactions and Synergistic Perspectives of Equol as a Potent Anticancer Isoflavone.

It is well known that, historically, plants have been an important resource of anticancer agents, providing several clinically approved drugs. Numerous preclinical studies have shown a strong anticancer potential of structurally different phytochemicals, including polyphenolic constituents of plants, flavonoids. In this review article, suppressing effects of equol in different carcinogenesis models are unraveled, highlighting the mechanisms involved in these anticancer activities. Among flavonoids, daidzein is a well-known isoflavone occurring in soybeans and soy products. In a certain part of population, this soy isoflavone is decomposed to equol under the action of gut microflora. Somewhat surprisingly, this degradation product has been shown to be more bioactive than its precursor daidzein, revealing a strong and multifaceted anticancer potential. In this way, it is important to bear in mind that the metabolic conversion of plant flavonoids might lead to products that are even more efficient than the parent compounds themselves, definitely deserving further studies.