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Immunization approaches are designed to stimulate the immune system and eliminate the tumor. Studies indicate that cancer immunization combined with certain chemotherapeutics and immunostimulatory agents can improve outcomes. Chemotherapeutics-based immunogenic cell death makes the tumor more recognizable by the immune system. In situ vaccination (ISV) utilizes established tumors as antigen sources and directly applies an immune adjuvant to the tumor to reverse a cold tumor microenvironment to a hot one. Immunogenic cell death and ISV highlight for the immune system the tumor antigens that are recognizable by immune cells and support a T-cell attack of the tumor cells. This review presents the concept of immunogenic apoptosis and ISV as a powerful platform for cancer immunization.

The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.

Cauliflower Mosaic Virus (CaMV) is a plant Pararetrovirus with a double-stranded DNA genome distributed worldwide. This study analyzed migration, evolution, and synonymous codon pattern of CaMV and the factors that shape it. We extracted genomic sequences of 121 isolates of CaMV, which were reported from various regions-hosts, from the NCBI database. The evolution of viruses has been widely studied by analyzing their nucleotides and coding regions/codons using different methods. Analysis of the CaMV phylogenetic tree shows that it divides most of the sequences into two main groups: Group I includes Irananin, Japanese, and American-European subgroups, and Group II includes Grecian, Turkish, and Iranian subgroups. Analysis of effective codon count, and relative codon deoptimization index, showed that natural selection is a major driving force in CaMV. Furthermore, Relative synonymous codon usage (RSCU) and neutrality analyses show that CaMV prefers A-ending codons and that one codon, namely GGA, was overrepresented. Analysis of dinucleotide composition demonstrates that nucleotide A was the most abundant in the CaMV coding sequences, and that the most frequent nucleotide at the third position of the codon was A3S. In CaMV, host adaptation was highest for Brassica oleracea and lowest for Raphanus sativus. Therefore the CaMV codon pattern is mostly shaped by the need to escape antiviral responses associated with host dinucleotides and translational efficiency. These values indicate that the study provides useful information on the codon usage analysis of CaMV and can be used to understand host adaptation to the virus environment and its evolution. This is the first study on codon usage bias of CaMV in the world.

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Red beetroot (Beta vulgaris) contains Betanin as its major betacyanin, possessing wide proapoptotic effects. This study aimed to investigate the anticancer and pro-papoptotic effects of beetroot hydro-alcoholic extract (BHE) and betanin, on colorectal cancer cell lines. BHE and betanin were used to treat Caco-2 and HT-29 colorectal cancer cells. MTT assay, DAPI staining, and FACS-flow cytometry tests were used to determine the half-maximal inhibitory concentration (IC50) and apoptosis-inducing evaluations. Intended genes were assessed by real-time polymerase chain reaction (RT-PCR). The IC50 for HT-29 and Caco-2 cell lines were 92 µg/mL, 107 µg/mL for BHE, and 64 µg/mL, 90 µg/mL for betanin at 48 h, respectively. BHE and betanin significantly inhibited the growth of both cancer cell lines time and dose-dependently. DAPI staining and flow cytometry results revealed significant apoptosis symptoms in treated cancerous cell lines. The expression level of proapoptotic genes (BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) in treated HT-29 and Caco-2 cells was higher than in untreated and normal cells. In contrast, the anti-apoptotic gene (Bcl-2) was significantly downregulated. BHE and betanin effectively inhibited cancer cell proliferation and induced apoptosis via the modification of effective genes.

Nowadays despite conventional methods in colon cancer treatment, targeting vital molecular pathways and induction of various forms of cell death by safe probiotic components like exopolysaccharides (EPSs) are of great importance and are considered as potential therapeutic agents. This study aimed to investigate the inhibitory effect of the EPS of L. paracasei on different colon cancer cell lines (SW-480, HT-29, and HCT-116). For this purpose, several cellular and molecular experiments including MTS assay, DAPI staining, Annexin V/PI assay, quantitative real-time PCR (qPCR) and some important ferroptosis-related assays were performed. Based on the findings, L. paracasei EPS can induce apoptosis confirmed by all apoptosis-related assays and could not act through ferroptosis pathways. L. paracasei EPS could hinder the Akt1, mTOR, and Jak-1 mRNAs, and induces apoptosis through down-regulation of the anti-apoptotic gene (Bcl-2), up-regulation of pro-apoptotic genes (BAX, caspase-3, 8). The exploited EPS of an indigenous probiotic strain with anticancer potential with low/insignificant cytotoxicity to normal cells is proposed for future applications in molecular-targeted therapy of colon cancer treatment. Furthermore, in vivo and clinical trials should be performed to evaluate the applicability of this component besides conventional methods to increase the survival rate of colon cancer patients.

The aim of the present study was to synthesize ZnO-TiO2/Au (Zn/Ti weight ratio of 1/1, the concentration of gold of 5–15 wt%) nanostructures using zinc acetate, titanium isopropoxide, and hydrogen tetra chloroauric through the sol-gel method. Physicochemical in vitro antifungal properties along with the morphological characterization are investigated via MIC, MFC, and ROS tests. All synthesized nanoparticles showed that A. flavus growth inhibition of ZnO-TiO2/Au (MIC = 0.625 μg/ml) showed higher antifungal activity against A. flavus at 15 wt% of Au than ZnO-TiO2 nanostructures (MIC = 78 μg/ml). Based on our findings, all of ZnO-TiO2/Au samples showed higher ROS production, which led to the induction of oxidative stress which is the reason of higher fungicide effect of Au-containing samples. In conclusion, the obtained Au-doped samples with enhanced chemical reactivity have a great potential for antifungal properties. Therefore, this work indicated ZnO-TiO2/Au has good potential with excellent clinical applications.

Background: Preclinical and clinical studies show that local and systemic antitumor efficacy is achievable by in situ vaccination (ISV) using plant virus nanoparticles in which immunostimulatory reagents are directly administered into the tumor rather than systemically. Aim: To investigate a minimally studied plant virus nanoparticle, alfalfa mosaic virus (AMV), for ISV treatment of 4T1, the very aggressive and metastatic murine triple-negative breast cancer model. Materials & methods: AMV nanoparticles were propagated and characterized. Their treatment impact on in vivo tumors were analyzed using determination of inherent immunogenicity, cytokine analysis, western blotting analysis and immunohistochemistry methodologies. Results: AMV used as an ISV significantly slowed down tumor progression and prolonged survival through immune mechanisms (p

This study aimed to screen alpha-amylase producing microorganisms from honey as a low water activity medium, a suitable source for selecting stable and cost-beneficial bacterial enzyme production systems. Plackett–Burman method was used to select twelve effective factors including pH, inoculum size, temperature, time, corn starch, KH2PO4, peptone, MgSO4, CaCl2, NaCl, glycerin, and yeast extract concentrations on bacterial alpha-amylases production yield. The Box–Behnken method was utilized to optimize the level of selected significant factors. The stability of bacterial alpha-amylases was also determined in low pH and high-temperature conditions. In addition, in silico study was used to create the alpha-amylase structure and study the stability in high-temperature and low water available condition. Among all isolated and characterized microorganisms, Bacillus megaterium produced the highest amount of alpha-amylases. The in silico data showed the enzyme 3D structure similarity to alpha-amylase from Halothermothrix orenii and highly negative charge amino acids on its surface caused the enzyme activity and stability in low water conditions. Based on Box–Behnken results, the temperature 35 °C, pH 6 and starch 40 g/l were determined as the optimum level of significant factors to achieve the highest alpha-amylases unit (101.44 U/ml). This bacterial alpha-amylases enzyme showed stability at pH 5 and a range of temperatures from 40 to 60 °C that indicates this enzyme may possess the potential for using in industrial processes.

Colon cancer is one of the most prevalent cancers, and intestinal microbial community plays a pivotal role in colorectal tumor genesis. Probiotics as live microorganisms may be able to exert an anticancer effect in colon cancer. The aim of this study was to isolate and identify Lactobacillus spp. from traditional dairy products with probiotic properties and to investigate their anticancer effects through ErbB-2 and ErbB-3 gene expression in colon cancer cells. The isolated lactobacilli from yogurt and cheese samples were molecularly identified by blasting of 16-23s rDNA region PCR sequenced products. The probiotic properties, including acid and bile tolerance, antimicrobial activity, and antibiotic susceptibility, were assayed. The proliferation inhibition effects of lactobacilli secretion metabolites with probiotic potential on colon cancer cell lines (HT-29 and caco-2) were analyzed using MTT assay. The real-time PCR was used for assessment of ErbB-2 and ErbB-3 gene expression after being treated with probiotics. Four species of bacteria with the most probiotic properties, including Lactobacillus casei, Lactobacillus paracasei, Lactobacillus rhamnosus, and Lactobacillus plantarum, were characterized and their effects on different human cell lines were taken into consideration. Total bacterial secretions significantly reduced the viability of HT-29 and caco-2 cancer cells compared with untreated controls. The metabolites secreted by bacteria downregulated the expression of ErbB-2 and ErbB-3 genes in colon cancer cells. The present study indicated that probiotic bacteria isolated from traditional dairy products exert anticancer effect on colon cancer cells through the downregulation of ErbB-2 and ErbB-3 gene expression.

The current study intended to evaluate two types of biorecognition element (BRE), namely recombinant antibody fragments and M13 bacteriophage-displayed antibody fragments, where protein L and electrostatic interactions were used to respectively conjugated antibodies and bacteriophages on AuNPs. The functionalization process was examined by DLS to monitor the changes in the size and zeta potential. The formation of the BRE-G17-Gly immunological complexes was manifested by aggregation (confirmed by FE-SEM) and color change from red to dark blue visible to the naked eye. Local refractive index variations of functionalized AuNPs were monitored by a UV - vis spectrophotometer, showing increasing size and decreasing zeta potential in all stages. The calibration plot was developed in the concentration range 1-5 µg/mL and the limit of detection (LOD) was 1 µg/mL. The LSRP nanobiosensor in combination with the phage-based BRE was an affordable and simple approach, as it was able to eliminate the time-consuming and costly step of extracting antibodies. Contrary to the traditional immunoassays, this method does not require additional amplification, e.g., enzymatic, to read the result. The proposed LSPR nanobiosensor model can be adapted to detect a wide range of pathogens, viruses, and biomarkers in the shortest possible time.

The effective treatment of glioma through conventional chemotherapy is proved to be a great challenge in clinics. The main reason is due to the existence of two physiological and pathological barriers respectively including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) that prevent most of the chemotherapeutics from efficient delivery to the brain tumors. To address this challenge, an ideal drug delivery system would efficiently traverse the BBB and BBTB and deliver the therapeutics into the glioma cells with high selectivity. Herein, a targeted delivery system was developed based on nanostructured lipid carriers (NLCs) modified with two proteolytically stable D-peptides, D8 and RI-VAP (Dual NLCs). D8 possesses high affinity towards nicotine acetylcholine receptors (nAChRs), overexpressed on brain capillary endothelial cells (BCECs), and can penetrate through the BBB with high efficiency. RI-VAP is a specific ligand of cell surface GRP78 (csGRP78), a specific angiogenesis and cancer cell-surface marker, capable of circumventing the BBTB with superior glioma-homing property. Dual NLCs could internalize into BCECs, tumor neovascular endothelial cells, and glioma cells with high specificity and could penetrate through in vitro BBB and BBTB models with excellent efficiency compared to non-targeted or mono-targeted NLCs. In vivo whole-animal imaging and ex vivo imaging further confirmed the superior targeting capability of Dual NLCs towards intracranial glioma. When loaded with Bortezomib (BTZ), Dual NLCs attained the highest therapeutic efficiency by means of superior in vitro cytotoxicity and apoptosis and prolonged survival rate and efficient anti-glioma behavior in intracranial glioma bearing mice. Collectively, the designed targeting platform in this study could overcome multiple barriers and effectively deliver BTZ to glioma cells, which represent its potential for advanced brain cancer treatment with promising therapeutic outcomes.

The tumor microenvironment (TME) within and around a tumor is a complex interacting mixture of tumor cells with various stromal cells, including endothelial cells, fibroblasts, and immune cells. In the early steps of tumor formation, the local microenvironment tends to oppose carcinogenesis, while with cancer progression, the microenvironment skews into a protumoral TME and the tumor influences stromal cells to provide tumor-supporting functions. The creation and development of cancer are dependent on escape from immune recognition predominantly by influencing stromal cells, particularly immune cells, to suppress antitumor immunity. This overall process is generally called immunoediting and has been categorized into three phases; elimination, equilibrium, and escape. Interaction of tumor cells with stromal cells in the TME is mediated generally by cell-to-cell contact, cytokines, growth factors, and extracellular vesicles (EVs). The least well studied are EVs (especially exosomes), which are nanoparticle-sized bilayer membrane vesicles released by many cell types that participate in cell/cell communication. EVs carry various proteins, nucleic acids, lipids, and small molecules that influence cells that ingest the EVs. Tumor-derived extracellular vesicles (TEVs) play a significant role in every stage of immunoediting, and their cargoes change from immune-activating in the early stages of immunoediting into immunosuppressing in the escape phase. In addition, their cargos change with different treatments or stress conditions and can be influenced to be more immune stimulatory against cancer. This review focuses on the emerging understanding of how TEVs affect the differentiation and effector functions of stromal cells and their role in immunoediting, from the early stages of immunoediting to immune escape. Consideration of how TEVs can be therapeutically utilized includes different treatments that can modify TEV to support cancer immunotherapy.

Background: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Fruit and vegetables have some active compounds such as flavonoids and polyphenols that protect against malignancies through their antioxidative, anti-inflammatory, anti-proliferative, neuro, and hepatoprotective properties. Red beetroot (Beta vulgaris) contains red (betacyanins) and yellow (betaxanthins) pigments known as betalains. Betanin makes up 75-95% of the total betacyanins, possessed a wide range of favorable biological effects such as chemopreventive, anticarcinogenic, anti-tumorogenic, antiangiogenic, and proapoptotic effects. Methods: Red beetroot hydro-alcoholic extract and betanin were used to treat Caco-2 and HT-29 colorectal cancer cells, as well as KDR/293 normal epithelial cells. The half-maximal inhibitory concentration (IC50) was determined by prescreening MTT tests in the range of 20 to 140 µg/ml at 24 and 48 h. The cytotoxicity and apoptosis-inducing evaluations were performed via MTT assay, DAPI staining, and FACS-flow cytometry tests using determined times and doses. Moreover, the expression level of six important genes involving in the apoptosis pathway (Bcl-2, BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) were determined using the real-time polymerase chain reaction (RT-PCR) method.Results: The IC50 doses for HT-29 and Caco-2 cell lines were determined to be about 92 μg/mL, 107 μg/mL for beetroot hydro-alcoholic extract, and 64 μg/mL, 90 μg/mL for betanin at 48 h, respectively. Our findings showed that beetroot extract and betanin significantly inhibit the growth of HT-29 and Caco-2 cell lines, time and dose-dependently, without considerable adverse effects on KDR/293 normal cells. Moreover, DAPI staining and flow cytometry results revealed significant apoptosis symptoms in treated cancerous cell lines. The expression level of pro-apoptotic genes involved in intrinsic and extrinsic apoptosis pathways (BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) in treated HT-29 and Caco-2 cells was higher than untreated and normal cells, whereas the anti-apoptotic gene (Bcl-2) was downregulated. Conclusion: Beetroot hydro-alcoholic extract and betanin significantly inhibited cell proliferation and induced cell apoptosis (intrinsic and extrinsic pathways) via modification of effective genes in both colorectal cancer cell lines with no significant cytotoxic effects on KDR/293 normal cells. The mechanism of the anticancer effects of red beetroot extract and betanin needs to be further studied.

Protease is a kind of enzyme with different applications in medicine and industry. The limitation of the enzymes in industry is lack of tolerance for harsh conditions (high temperature, pH, and low water condition). This study intends to evaluate in silico study and screen the alkaline serine protease producing bacteria from honey and optimize the production of low water active alkaline serine protease. Plackett–Burman method was applied to improve effective factors on protease production, including pH, inoculum size, temperature, time, soybean protein, KH2PO4, MgSO4, CaCl2, NaCl, Glycerin and glucose concentration. Further, the Box–Behnken method was used to optimize the significant level of selected factors. Besides, in silico study was utilized to create the enzyme structure and investigate the stability in harsh conditions. The results showed that the highest protease production belongs to Bacillus sp. Khoz1 closed Bacillus safensis, Also temperature, glucose and soybean protein concentration were three significant factors for protease production and the optimized level for them were 35 °C, 0.5 g/l, and 38.32 g/l, respectively. The microorganism was able to produce protease until 98.36 U/ml and it was 98.68% similar to B. safensis. The stability of microbial alkaline serine protease was also determined in high pH and temperature conditions. The best stable condition for isolated protease was pH 9 and temperature at 50 °C. The in silico data showed that this protease has similar 3D structure to Bacillus subtilis Subtilisin E and highly charge amino acids on its surface were that caused this enzyme still activate and stable in low water condition.

The paper in hand seeks to evaluate the tumor-suppressive and apoptotic effects of L. paracasei X12 in 1, 2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. The rats were divided into three groups (n = 8-12 per group); L. paracasei X12 was administrated to these animals for forty weeks. The findings of this study indicated that L. paracasei X12 administration prevented severe weight loss in DMH-treated rats. It was also determined that L. paracasei X12 administration could prevent the neoplasia incidence, cell proliferation and it also could suppress the tumors’ growth. Additionally, a significant improvement was observed in apoptosis indexes and cell proliferation in probiotic-treated rats. In conclusion, this study provides insights into the therapeutic potential of L. paracasei X12 with emphasis on the issue that modulation of apoptosis pathway could leave beneficial effects in the prevention and suppression of colorectal cancer (CRC). However, further studies are in support to clarify the mechanisms involved in the tumor-suppressive effect of probiotics.

According to the latest statistics, cancer is expected to account for nearly 1800000 new cases and about 607000 deaths in the US in 2019. Approximately 40% of people with cancer survive. This means that life expectancy is a little more than 1 in 3. Therefore, it is essential to detect this malignancy in early stage and predict therapeutic responses in patients in order to enhance the efficiency of treatment, decrease side-effects and optimize the cure process. One of the best solutions for early cancer diagnosis and management is tracking tumor markers. Cancerous or noncancerous cells produce these substances in response to cancer or some specific conditions. Although, onco-biomarkers are generated in normal situations, their concentration is much higher in the presence of tumors. These materials which most of them are proteins can be spotted in body fluids such as blood, serum and urine. An increased level of an oncobiomarker may be associated with the presence of cancer, however, it is not a definite indicator. For that reason, a combination of biomarkers and other diagnostic tests are always preferred. Due to the high cost, low speed and intricate instrumental requirements of existing assays such as enzyme linked immuno-sorbent assay, fluorescence and radiometric immunoassay for measurement of biomarkers, there is an extreme need for more inexpensive, swift, simple and portable detection methods. In recent years, the popularity of electrochemical biosensors are increasing in diagnostic fields. Significant improvements in electrochemical techniques, biological instrumentation and nanotechnology have paved the way for the emergence of novel platforms for detection of tumor markers. Importance of measurement of biomarkers by electrochemical-based affinity biosensors for early cancer diagnosis and monitoring have been emphasized by numerous articles. The main purpose of the present review is to give researchers a general idea of the recent studies about early cancer detection by EC-based biosensing devices, being pursued globally.

Purpose: This study aimed to improve the pharmacokinetic behavior of polyunsaturated fatty acids (PUFAs) oxidation to enhance oxidative stability for inhibiting formation of toxic hydroperoxides, develops off-flavors and shortens shelf-life. Methods: Nanostructured lipid carrier (NLC) co-encapsulating omega-3 fish oil and α-tocopherol was successfully prepared by melt blending and hot sonication method to enhance the oxidative stability of the fish oil. Encapsulation efficiency (EE) and in vitro release, the oxidative stability of prepared nanoparticles (NPs) were measured using detection of peroxide value (PV) and thiobarbituric acid (TBA) during 40 days. Results: Electron microscopy and particle size analysis showed dispersed and homogenous NPs with an average diameter of 119 nm. Sustained oil release at a physiologic pH, and longterm stability in terms of the size, zeta, and dispersity of NPs was achieved after 75 days of storage. The omega-3 fish oil co-encapsulated with α-tocopherol in the NLC possessed better oxidative stability compared with the all other formulations. Also, it was found that the NLC as an encapsulation method was more successful to inhibit the formation of the primary oxidation products than the secondary oxidation products. Conclusion: Generally, these findings indicated that co-encapsulation of fish oil and α-tocopherol within the NLC can be a suitable delivery system in order to enrich foodstuffs, in particular clear beverages.

Several scientific evidences have revealed probiotics implications on human health. A wide range of lactic acid bacteria (LAB) have been extensively studied for their ability to produce extracellular polysaccharides (EPSs), which are repeating units of mono/oligosaccharides with various chemical compositions and properties. Despite the conventional belief regarding probiotics that states bacteria must be alive to exert their beneficial effects, mounting evidence opened up new perspectives on health-promoting effects of bacterial-derived molecules/metabolites. Employing EPSs seems safer alternative in complicated disorders like cancer and immune related diseases. EPSs have potential applications in textiles, cosmetology, wastewater treatment, food, and pharmaceutical industries, but little is known about their function therefore the present review aims to discuss the health-promoting properties of EPSs produced by LAB. Antioxidant, antiviral, antitumor and immunomodulating activity, with focus on the mechanisms involved, are discussed in the study. Ever-growing number of researches indicate that EPSs beneficiary effects have a promising future ahead.

Thousands of billions of dollars have been disbursed worldwide for the diagnosis and therapy of disease. Nanobioscience combined with sensing technology has facilitated the pathway to diagnosis by introducing a novel, highly sensitive and selective detection system known as the nanobiosensor to reduce the overall cost of treatment. Among the many types of biosensors, optical ones are more easily developed because of their low cost, rapid construction, small size, high performance, high sensitivity and selectivity, high signal-to-noise ratio, flexible geometry, and portability properties. This study reviews and discusses nanobiosensors and electrochemical biosensors with the main focus on colorimetric, fluorometric, luminometric, fiber optic, and surface plasmon resonance-based optical biosensors and an emphasis on their applications in medical diagnosis.

This study aimed to synthesis ZnO, TiO

A growing literature indicates several health benefits of theanine, a major nonprotein derivative amino acid special to tea, and a nonedible mushroom. This study aimed to systematically review the scientific evidence regarding the anticarcinogen and anticancer effects of natural theanine. A systematic search for the relevant articles published until January 2021 on MEDLINE, Scopus, and Web of Knowledge was conducted. Out of 377 initial records, 14 in vitro, ex vivo, and in vivo studies met our inclusion criteria. Most of the included in vitro and ex vivo studies reported beneficial effects of theanine on the proliferation, apoptosis, metastasis, migration, and invasion in various cancer cell lines. The in vivo studies also supported the potential impacts of theanine on cancer incidence or progression. Theanine exerted its anticancer function by inhibiting EGFR, VEGFR, Met, and Akt/mTOR, JAK2/STAT3, and ERK/NFκB pathways, as well as activating the intrinsic apoptosis pathway and caspase-independent programmed cell death. In conclusion, the results indicated moderate apoptotic, antimetastatic, antimigration, and anti-invasion effects, along with the mild antiproliferative influence of theanine on cancer. Further studies are necessary to ascertain the effectiveness of theanine on the prevention and suppression of cancer and shed light upon the attributable mechanisms in the in vivo condition.

This study aimed to investigate the effect of theobromine on dimethylhydrazine (DMH)-induced colon cancer. Male Wistar rats were divided into four groups and injected with saline (negative control) or 30 mg/kg DMH (other three groups) two times a week for 12 weeks. The negative control and DMH-treated control rats were treated with water and the other two groups with theobromine, at the dose of 100 or 200 mg/kg, two weeks before and during the period of injection. Both doses of theobromine reduced the volume and number of tumors, the number of aberrant crypts, and the expression of p-Akt, p-GSk3β, and cyclinD1, and also increased the expression of APC tumor suppressor. A significant reduction in the expression of β-catenin was observed in the rats treated with the high dose of theobromine. The results indicated that theobromine may be an effective chemopreventive agent for colon cancer by inhibition of the Akt/GSk3β/β-catenin pathway.

Some evidence suggests that caffeine, theophylline, and theobromine, as natural methylxanthines (MTXs), possess anti-cancer effects. We systematically reviewed the animal and human studies investigating the effect of (or association between) dietary natural MTXs on (and) colorectal cancer (CRC) and performed a meta-analysis of epidemiological studies. Relevant studies were identified by searching MEDLINE, Embase, Scopus, and Web of Knowledge through September 2020. The overall relative risk (RR) and confidence interval (CI) were determined using a random-effects model. Eight animal and eight epidemiological investigations met our inclusion criteria. Animal studies indicated detrimental effects of high levels of caffeine intake on the initiation and promotion of CRC, while showing beneficial or non-significant effects at lower doses. The meta-analysis of six epidemiological studies found no association between dietary caffeine intake and the risk of CRC (RR = 0.98 (95% CI = 0.88–1.10)). Subgroup analysis revealed a direct association between caffeine intake and risk of CRC only in the studies with a moderate risk of bias and a lack of adjustment for smoking. The results of the only epidemiological study investigating the association between the serum levels of MTXs and the risk of CRC showed an inverse association. In conclusion, some animal studies underlined the beneficial effects of caffeine, at regular doses consumed by humans, on CRC. However, current epidemiological evidence does not support an association between caffeine intake and the risk of CRC.

Background: Betanin makes up 75-95% of the total betacyanins, possessed a wide range of favorable biological effects such as chemopreventive, anticarcinogenic, anti-tumorogenic, antiangiogenic, and proapoptotic effects. Methods: Hydro-alcoholic extract of red beetroot and betanin were used to treat Caco-2 and HT-29 colorectal cancer cells, as well as KDR-293 normal epithelial cells. The half-maximal inhibitory concentration (IC50) was determined by prescreening MTT tests in the range of 20 to 140 µg/ml at 24 and 48 h. The cytotoxicity and apoptosis-inducing evaluations were performed via MTT assay, DAPI staining, and FACS-flow cytometry tests using determined time and doses. Results: The IC50 doses for HT-29 and Caco-2 cell lines were determined to be about 92 μg/mL, 107 μg/mL for beetroot hydro-alcoholic extract and 64 μg/mL, 90 μg/mL for betanin at 48 h, respectively. Our findings showed that beetroot hydro-alcoholic extract and betanin significantly inhibit the growth of HT-29 and Caco-2 cell lines, time, and dose-dependently, without considerable adverse effects on KDR/293 normal cells. Moreover, DAPI staining and flow cytometry results revealed significant apoptosis symptoms in treated cancerous cell lines. Conclusion: Betanin effectively inhibited cell growth in both colorectal cancer cell lines with no significant cytotoxic effects on the KDR/293 normal cells. The mechanism of the anticancer effects of red beetroot hydro-alcoholic extract and betanin needs to be further studied.

In this research, four novel and sensitive immunosensors for electrochemical determination of G17-Gly were designed based on signal amplification and tailor-made recombinant antibody technology. Anti-G17-Gly antibody fragments (i.e. scFv and VL specific to the N- and C-terminal of G17-Gly) were immobilized onto a polymeric nanocomposite comprising poly cetyl trimethyl ammonium bromide (P(CTAB)) as the conductive matrix, chitosan (CS) as a biocompatible agent and gold nanoparticles (AuNPs) as the signal amplification element. The high surface area provided by AuNPs and the small size of scFv/VL establish the basis for immobilizing a high amount of the anti-G17-Gly on the surface of the electrode for detecting G17-Gly in human plasma samples. Under optimal conditions, the designed immunosensors provide an excellent analytical capability for detecting and determining G17-Gly in human plasma samples with a linear range from 0.5 mM to 0.05 pM and a LLOQ of 0.05 pM. The sensitivity order of the immunosensors was Ag/2-mercaptoethanol/phage displaying scFv/P(CTAB–CS)–AuNP/GE, Ag/2-mercaptoethanol/phage displaying VL/P(CTAB–CS)–AuNP/GE, Ag/BSA/scFv/P(CTAB–CS)–AuNP/GE, and Ag/BSA/VL/P(CTAB–CS)–AuNP/GE. The aforementioned characteristics demonstrate that the proposed immune-devices can be used in biological and clinical diagnosis as reliable tools for identifying different oncobiomarkers.