In silico design of potential Mcl-1 peptide-based inhibitors.

CONTEXT: BIM (Bcl-2 interacting mediator of apoptosis)-derived peptides that specifically target over-expressed Mcl-1 (myeloid cell leukemia-1) protein and induce apoptosis are potentially anti-cancer agents. Since the helicity of BIM-derived peptides has a crucial role in their functionality, a range of strategies have been used to increase the helicity including the introduction of unnatural residues and stapling methods that have some drawbacks such as the accumulation in the liver. To avoid these drawbacks, this study aimed to design a more helical peptide by utilizing bioinformatics algorithms and molecular dynamics simulations without exploiting unnatural residues and stapling methods. MM-PBSA results showed that the mutations of A4fE and A2eE in analogue 5 demonstrate a preference towards binding with Mcl-1. As evidenced by Circular dichroism results, the helicity increases from 18 to 34%, these findings could enhance the potential of analogue 5 as an anti-cancer agent targeting Mcl-1. The applied strategies in this research could shed light on the in silico peptide design. Moreover, analogue 5 as a drug candidate can be evaluated in vitro and in vivo studies. METHODS: The sequence of the lead peptide was determined using the ApInAPDB database and PRALINE program. Contact finder and PDBsum web server softwares were used to determine the contact involved amino acids in complex with Mcl-1. All identified salt bridge contributing residues were unaltered to preserve the binding affinity. After proposing novel analogues, their secondary structures were predicted by Cham finder web server software and GOR, Neural Network, and Chou-Fasman algorithms. Finally, molecular dynamics simulations run for 100 ns were done using the GROMACS, version 5.0.7, with the CHARMM36 force field. MM-PBSA was used to assess binding affinity specificity in targeting Mcl-1 and Bcl-xL (B-cell lymphoma extra-large).

Immunotherapeutic effect of photothermal-mediated exosomes secreted from breast cancer cells.

Aim: Exosomal damage-associated molecular patterns can play a key role in immunostimulation and changing the cold tumor microenvironment to hot. Materials & methods: This study examined the immunostimulation effect of photothermal and hyperthermia-treated 4T1 cell-derived exosomes on 4T1 cell-induced breast tumors in BALB/c animal models. Exosomes were characterized for HSP70, HSP90 and HMGB-1 before injection into mice and tumor tissues were analyzed for IL-6, IL-12 and IL-1ß, CD4 and CD8 T-cell permeability, and PD-L1 expression. Results: Thermal treatments increased high damage-associated molecular patterns containing exosome secretion and the permeability of T cells to tumors, leading to tumor growth inhibition. Conclusion: Photothermal-derived exosomes showed higher damage-associated molecular patterns than hyperthermia with a higher immunostimulation and inhibiting tumor growth effect.

This research explored the impact of using tiny dying cancer cell-derived particles known as exosomes to activate the immune system to fight against breast tumors in animal models. These exosomes contain specific molecules that can trigger the immune response and alter the environment surrounding the tumor. Researchers applied two different treatments, photothermal and hyperthermia, to kill the cancer cells and obtain these exosomes. Both treatments involved using heat to kill the cells. The study revealed that exosomes derived through the photothermal method exhibited higher levels of these immune-activating molecules compared with those obtained through hyperthermia. Upon injecting these exosomes into the animal models, they enhanced the ability of the immune cells to enter the tumors, resulting in a reduction in tumor growth. Overall, the findings indicate that using exosomes obtained through the photothermal method may be more effective in stimulating the immune system to fight against cancer and inhibiting tumor growth, as opposed to using exosomes obtained through hyperthermia.

In vitro siRNA-mediated GPX4 and AKT1 silencing in oxaliplatin resistance cancer cells induces ferroptosis and apoptosis.

Oxaliplatin is a member of platinum-based chemotherapy drugs frequently used in colorectal cancer (CRC). However, resistance to oxaliplatin causes tumor progression and metastasis. Akt1 and Gpx4 are essential regulator genes of apoptosis and ferroptosis pathways. Inhibition of these genes might eradicate oxaliplatin resistance in resistant CRC cells. We compared two cell death strategies to reverse drug resistance in Caco-2 and HT-29 oxaliplatin-resistant cell lines. We used the AKT1-specific siRNA to induce apoptosis. Also, GPX4-specific siRNA and FIN56 were utilized to generate ferroptosis. The effect of these treatments was assessed by reactive oxygen species (ROS) formation, cell viability, and protein expression level assays. Besides, the expression of GPX4, CoQ10, and NRF2 was assessed in both cell lines after treatments. Correctly measuring the expression of these responsible genes and proteins confirms the occurrence of different types of cell death. In addition, the ability of Akt1/ GPX4 siRNA in resensitizing HT-29 and Caco-2 oxaliplatin resistance cells was evaluated. Our finding showed that the upregulation of GPX4/siRNA caused a reduction in GPX4 and CoQ10 expressions in both cell lines. However, the expression level of NRF2 showed the same level in our cell lines, so we observed a downregulation of NRF2 in resistant CRC cell lines. Cell viability assay indicated that induction of ferroptosis by GPX4/siRNA or FIN56 and apoptosis by Akt1/siRNA in resistant cell lines could reverse the oxaliplatin resistance. We concluded that downregulation of Akt1 or Gpx4 could increase the efficacy of oxaliplatin to overcome the resistance compared to FIN56.

Anticancer properties of red beetroot hydro-alcoholic extract and its main constituent; betanin on colorectal cancer cell lines.

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.

Combining in situ vaccination and immunogenic apoptosis to treat cancer.

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 immune system recognizes and attacks tumors, but often the tumor is able to protect itself by generating a local immune suppressive environment that reduces antitumor immune response. Therapies such as immune checkpoint blockade antibodies are meant to overcome immune suppression and enable an effective antitumor immune response; however, many patients do not respond to immune checkpoint blockade therapy. Further immune manipulations are needed to improve the response to immune-based cancer treatments. Approaches that reverse the tumor-mediating immune suppression can be effective. This review discusses combining two such approaches, generating immunogenic cell death of tumor cells and treating recognized tumors with immune stimulatory reagents, called in situ vaccination or intratumoral immunotherapy.

ApInAPDB: a database of apoptosis-inducing anticancer peptides.

ApInAPDB (Apoptosis-Inducing Anticancer Peptides Database) consists of 818 apoptosis-inducing anticancer peptides which are manually collected from research articles. The database provides scholars with peptide related information such as function, binding target and affinity, IC50 and etc. In addition, GRAVY (grand average of hydropathy), net charge at pH 7, hydrophobicity and other physicochemical properties are calculated and presented. Another category of information are structural information includes 3D modeling, secondary structure prediction and descriptors for QSAR (quantitative structure-activity relationship) modeling. In order to facilitate the browsing process, three types of user-friendly searching tools are provided: top categories browser, simple search and advanced search. Overall ApInAPDB as the first database presenting apoptosis-inducing anticancer peptides can be useful in the field of peptide design and especially cancer therapy. Researchers can freely access the database at http://bioinf.modares.ac.ir/software/ApInAPDB/ .

Green Synthesis of Near-Infrared Copper-Doped Carbon Dots from Alcea for Cancer Photothermal Therapy.

Heteroatom-doped carbon dots (CDs) with optical absorbance in the near-infrared (NIR) region can provide an opportunity for selective cancer photothermal therapy (PTT). Here, an eco-friendly, simple, cost-efficient, and one-step hydrothermal method was developed to synthesize copper-doped CDs (Cu-doped CDs). The Alcea extract as the carbon source was combined with CuSO4 as the dopant. Microscopic and spectroscopic analyses showed that spherical and monodisperse Cu-doped CDs (Cu-dCDs) with sizes below 10 nm have bright fluorescence with photoluminescence quantum yields of 11.1%. Cu-dCDs exhibited an excellent single absorbance peak at 800 nm and strong emission at 460 nm when excited at 370 nm. In vitro low cytotoxicity and the Cu-dCD-mediated cell PTT with the photothermal conversion efficiency (39.3%) show that cell internalization of Cu-doped CDs under an 800 nm NIR laser can induce cell thermal death.

Enhanced BBB and BBTB penetration and improved anti-glioma behavior of Bortezomib through dual-targeting nanostructured lipid carriers.

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.

Tumor-Derived Extracellular Vesicles in Cancer Immunoediting and Their Potential as Oncoimmunotherapeutics.

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.

Alfalfa mosaic virus nanoparticles-based in situ vaccination induces antitumor immune responses in breast cancer model.

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 < 0.001). Conclusion: Mechanistic studies show that ISV with AMV increases costimulatory molecules, inflammatory cytokines and immune effector cell infiltration and downregulates immune-suppressive molecules.

Cell surface GRP78: An emerging imaging marker and therapeutic target for cancer.

As one of the deadliest diseases, cancer frequently resists existing therapeutics because they do not target all cells within a progressing tumor, for example both tumor stem and proliferating cells. This frequently results in enrichment of invasive and metastatic drug-resistant tumor cells subpopulations, cancer recurrence and eventually, patient mortality. Thus, there is an urgent need to identify specific markers, by which the targeted imaging and/or therapeutic "guided missile"-like agents can specifically detect and/or eradicate all cancer cells within a heterogeneous tumor, while leaving the normal cells intact. As a member of heat shock protein 70 (HSP70) superfamily, glucose regulated protein 78 (GRP78) has been documented as a molecular chaperone in the endoplasmic reticulum (ER) which mainly responds to ER stresses in normal cells. There is over-expression of GRP78 on the surface of cancer cells and angiogenic endothelial cells, which makes it a promising target for different types of peptides and antibodies that can be employed for targeted cancer therapy or imaging. In this review, we discuss the biological processes, functional importance and translocation mechanisms of cell surface GRP78 (csGRP78) in tumor cells. As a cancer biomarker, we also review the potential applications of csGRP78 targeted therapy and imaging and finally we suggest a brief roadmap ahead of csGRP78 targeting for targeted theranostic implications.

Recent progress on developing of plasmon biosensing of tumor biomarkers: Efficient method towards early stage recognition of cancer.

Cancer is the second most extended disease with an improved death rate over the past several time. Due to the restrictions of cancer analysis methods, the patient's real survival rate is unknown. Therefore, early stage diagnosis of cancer is crucial for its strong detection. Bio-analysis based on biomarkers may help to overcome the problem Biosensors with high sensitivity and specificity, low-cost, high analysis speed and minimum limit of detection are practical alternatives for laboratory tests. Surface plasmon resonance (SPR) is reaching a maturity level sufficient for their application in detection and determination cancer biomarkers in clinical samples. This review discusses main concepts and performance characteristics of SPR biosensor. Mainly, it focuses on newly emerged enhanced SPR biosensors towards high-throughput and ultrasensitive screening of cancer biomarkers such as PSA, α-fetoprotein, CEA, CA125, CA 15-3, HER2, ctDNA, ALCAM, hCG, VEGF, TNF, Interleukin, IFN-γ, CD24, CD44, Ferritin, COLIV using labeling processes with focusing on the future application in biomedical research and clinical diagnosis. This article reviews current status of the field, showcasing a series of early successes in the application of SPR for clinical bioanalysis of cancer related biomolecules and detailing a series of considerations regarding sensing schemes, exposing issues with analysis in biofluids, while providing an outlook of the challenges currently associated with plasmonic materials, bioreceptor selection, microfluidics, and validation of a clinical bioassay for applying SPR biosensors to clinical samples. Research opportunities are proposed to further advance the field and transition SPR biosensors from research proof-of-concept stage to actual clinical usage.

Effects of quercetin loaded nanostructured lipid carriers on the paraquat-induced toxicity in human lymphocytes.

Paraquat (PQ) as a herbicide and an environmental pollutant with increasing importance due to its toxicity to humans and animals. This study aimed to evaluate the protective and antioxidant activity of quercetin loaded Nanostructured Lipid Carriers (QNLC) against toxicity induced by PQ. Blood lymphocytes were prepared using Ficoll polysaccharide and subsequently by gradient centrifugation. The QNLC was prepared using an ultra-sonication method, which was characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The viability, reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosome membrane integrity, Bax and Bcl2 gene expression were evaluated in human isolated lymphocytes. The results showed spherical QNLCs with nano-size range (52.7 nm) and high drug encapsulation efficiency (98.5% -96%). The results also indicated that PQ induced cell death, as well as ROS production, decreased by QNLC in human lymphocytes. Also, QNLC meaningfully restored MMP reduction, lysosomal membrane destabilization, and lipid peroxidation and were capable of preventing PQ-treated change in Bax and Bcl2 gene expression. We report that QNLC, have a significantly higher capacity to prevent PQ-induced toxicity than Q itself. It is suggested that the QNLC is a promising antioxidant for drug delivery to be used as a therapeutic and prophylactic agent for PQ poisoning.

Application of Probiotics in Folate Bio-Fortification of Yoghurt.

Folate deficiency is a public health concern affecting all age groups worldwide. The available evidence reveals that adding probiotic bacteria to the yoghurt starter cultures during yoghurt production process under fermentation conditions increases the folate content of yoghurt. The present study was conducted to measure two folate derivatives, i.e., 5-methyltetrahydrofolate and 5-formyltetrahydrofolate, in bio-fortified yoghurt samples including (1) yoghurt containing Streptococcus thermophilus and Lactobacillus bulgaricus, (2) probiotic yoghurt containing Lactobacillus acidophilus LA-5 and Bifidobacterium lactis BB-12, (3) probiotic yoghurt containing native strains of Lactobacillus plantarum 15HN, (4) probiotic yoghurt containing native strains of Lactococcus lactis 44Lac, and (5) probiotic yoghurt containing commercial strains of Lactobacillus plantarum LAT BY PL. During storage at 4 °C for 21 days, the highest levels of 5-methyltetrahydrofolate and 5-formyltetrahydrofolate, which were statistically significant, were detected in the yoghurt made using Lact. plantarum 15HN. Moreover, the highest total folate concentration (1487 ± 96.42 µg/L) was specified in the yoghurt containing Lact. plantarum 15HN on the 7th day. It can be conjectured that this product can be suggested as a proper alternative to synthetic folic acid and may not have the side effects of using synthetic folic acid overdoses.

Prophylactic effects of secretion metabolites of dairy lactobacilli through downregulation of ErbB-2 and ErbB-3 genes on colon cancer cells.

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.

Natural low- and high-density lipoproteins as mighty bio-nanocarriers for anticancer drug delivery.

Lipoproteins (LPs) are a set of naturally occurring bio-nanoparticles consisting of Apo-LPs, phospholipids, a highly hydrophobic core of cholesteryl esters and triglycerides that participate mainly in the targeted transport of cholesteryl esters and other hydrophobic molecules through the bloodstream. They also are able to recognize specific receptors on normal and abnormal cells. Therefore, LPs represent a relevant tool for targeted delivery of cancer diagnostics and therapeutics due to their native biocompatibility, biodegradability, nano-scale size and receptor-mediated uptake. The circulating LPs are categorized into five classes, each with its own characteristic protein and lipid composition. Low-density LPs (LDL) and high-density LPs (HDL) are two major subclasses of LPs which were extensively subjected to attractive and versatile vehicles for targeted delivery of anticancer drugs. This study focus to highlight the potential applications of LDL and HDL bio-nanocarriers in the field of specific target drug delivery to cancer cells.

Novel angiotensin receptor blocker, azilsartan induces oxidative stress and NFkB-mediated apoptosis in hepatocellular carcinoma cell line HepG2.

Overexpression of renin angiotensin system (RAS) components and nuclear factor-kappa B (NF-kB) has a key role in various cancers. Blockade of RAS and NF-kB pathway has been suggested to reduce cancer cell proliferation. This study aimed to investigate the role of angiotensin II and NF-kB pathway in liver hepatocellular carcinoma cell line (HepG2) proliferation by using azilsartan (as a novel Ag II antagonist) and Bay 11-7082 (as NF-kB inhibitor). HepG2 cells were treated with different concentrations of azilsartan and Bay 11-7082. Cytotoxicity was determined after 24, 48, and 72?h by MTT assay. Reactive oxygen spices (ROS) generation and cytochrome c release were measured following azilsartan and Bay11- 7082 treatment. Apoptosis was analyzed qualitatively by DAPI staining and quantitatively through flow cytometry methodologies and Bax and Bcl-2 mRNA and protein levels were assessed by real time PCR and ELISA methods, respectively. The cytotoxic effects of different concentration of azilsartan and Bay11- 7082 on HepG2 cells were observed as a reduction in cell viability, increased ROS formation, cytochrome c release and apoptosis induction. These effects were found to correlate with a shift in Bax level and a downward trend in the expression of Bcl-2. These findings suggest that azilsartan and Bay11- 7082 in combination or alone have strong potential as an agent for prevention or treatment of liver cancer after further studies.

Selenium-Enriched Saccharomyces cerevisiae Reduces the Progression of Colorectal Cancer.

Colorectal cancer is one of the most common causes of mortality in the world while malnutrition is responsible for one third of the problem. Selenium has been recommended for prevention of colorectal cancer. The present study was conducted to investigate the effect of selenium-enriched Saccharomyces cerevisiae in reducing colorectal cancer progression in rats. Five groups of 170-200-g weight rats (n = 40) including healthy and cancer controls, Saccharomyces cerevisiae, selenium, and selenium-enriched Saccharomyces cerevisiae-treated groups were examined. All animals except healthy control group received 40 mg 1,2-dimethylhydrazine (DMH) per kilogram weight of rat twice a week. The healthy group received normal saline, and synchronously, selenium group received soluble selenium (4 mg/mL), Saccharomyces cerevisiae and selenium-enriched groups received yeast with the density of 5 × 108 CFU/mL by daily gavage. All treatments were carried out for 5 weeks after the last injection. Animals were autopsied, and aberrant crypt foci (ACF) of ejected colon were studied in the 40th week. Microscopic sections were prepared for hematoxylin and eosin. Furthermore, immunohistochemical staining of CD31, BCL2, and P53 antibodies was performed. Macroscopic and microscopic evaluations showed that DMH had the least destructive effect in selenium-enriched Saccharomyces cerevisiae group compared to other groups. Selenium-enriched Saccharomyces cerevisiae reduces colorectal cancer progression by various mechanisms such as reduction in the number and size of ACF and alteration in the function of the proteins such as P53, BCL2, and CD31.

Betanin reduces organophosphate induced cytotoxicity in primary hepatocyte via an anti-oxidative and mitochondrial dependent pathway.

Organophosphates (OP) are potent pesticide commonly utilized in agricultural and domestic use. However, plentitude of data represent their side effects in different body tissues. We attempted to study whether betanin (a natural pigment) is able to mitigate some OPs-induced hepatotoxicity in primary rat hepatocytes. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), glutathione (GSH) depletion and mitochondrial depolarization were tested as toxicity markers. The outcomes revealed that betanin (25µM) significantly increased cell viability, plummeted ROS formation and LPO, restored cellular GSH reservoirs and protected mitochondria after chlorpyrifos (CPF) (300µM), diazinon (DZN) (600µM) and dichlrovos (DDVP) (400µM) treatment. Taken together, all data suggests the potential protective role of betanin in OPs-induced hepatotoxicity in which the mechanism appears to be inhibition of ROS formation and mitochondrial protection.

Isolation and characterization of probiotics from dairies.

BACKGROUND AND OBJECTIVES: Probiotics are live microorganisms, which show beneficial health effects on hosts once consumed in sufficient amounts. LAB group can be isolated and characterized from traditional dairy sources. This study aimed at isolating, identifying, and in vitro characterizing (low pH/high bile salt tolerance, antibacterial activity, and antibiotic susceptibility) LAB strains from traditional Iranian dairy products. MATERIALS AND METHODS: Isolated strains were identified by Gram staining, catalase assay, and 3 molecular identification methods; namely, (GTG) 5-PCR fingerprinting, ARDRA, and 16S rDNA gene sequencing. RESULTS: A total of 19 LAB strains belonging to 4 genera (Lactococcus, Leuconostoc, Lactobacillus and Enterococcus) were identified. CONCLUSION: The experiments revealed that L. plantarum 15HN, L. lactis subsp. cremoris 44L and E. mundtii 50H strains, which were isolated from shiraz, cheese and shiraz, respectively, displayed a desirable tolerance to low pH and high bile salts, favorable anti-pathogen activity, and acceptable antibiotic susceptibility; hence, they could be considered as novel probiotic candidates and applied in the food industry.