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At least half the population in industrialized countries suffers from obesity due to excessive accumulation of adipose tissue. Recently, rice ( Oryza sativa ) proteins have been considered valuable sources of bioactive peptides with antiadipogenic potential. In this study, the digestibility and bioaccessibility in vitro of a novel protein concentrate (NPC) from rice were determined through INFOGEST protocols. Furthermore, the presence of prolamin and glutelin was evaluated via SDS-PAGE, and their potential digestibility and the bioactivity of ligands against peroxisome proliferator-activated receptor gamma (PPARγ) were explored by BIOPEP UWM and HPEPDOCK. For the top candidates, molecular simulations were conducted using Autodock Vina to evaluate their binding affinity against the antiadipogenic region of PPARγ and their pharmacokinetics and drug-likeness using SwissADME. Simulating gastrointestinal digestion showed a recovery of 43.07% and 35.92% bioaccessibility. The protein banding patterns showed the presence of prolamin (57 kDa) and glutelin (12 kDa) as the predominant proteins in the NPC. The in silico hydrolysis predicts the presence of three and two peptide ligands in glutelin and prolamin fraction, respectively, with high affinity for PPARγ (≤160). Finally, the docking studies suggest that the prolamin-derived peptides QSPVF and QPY (-6.38 & -5.61 kcal/mol, respectively) have expected affinity and pharmacokinetic properties to act as potential PPARγ antagonists. Hence, according to our results, bioactive peptides resulting from NPC rice consumption might have an antiadipogenic effect via PPARγ interactions, but further experimentation and validation in suitable biological model systems are necessary to gain more insight and to provide evidence to support our in silico findings.

The origin of cancer remains one of the most important enigmas in modern biology. This paper presents a hypothesis for the origin of carcinomas in which cellular aging and inflammation enable the recovery of cellular plasticity, which may ultimately result in cancer. The hypothesis describes carcinogenesis as the result of the dedifferentiation undergone by epithelial cells in hyperplasia due to replicative senescence towards a mesenchymal cell state with potentially cancerous behavior. In support of this hypothesis, the molecular, cellular, and histopathological evidence was critically reviewed and reinterpreted when necessary to postulate a plausible generic series of mechanisms for the origin and progression of carcinomas. In addition, the implications of this theoretical framework for the current strategies of cancer treatment are discussed considering recent evidence of the molecular events underlying the epigenetic switches involved in the resistance of breast carcinomas. The hypothesis also proposes an epigenetic landscape for their progression and a potential mechanism for restraining the degree of dedifferentiation and malignant behavior. In addition, the manuscript revisits the gradual degeneration of the nonalcoholic fatty liver disease to propose an integrative generalized mechanistic explanation for the involution and carcinogenesis of tissues associated with aging. The presented hypothesis might serve to understand and structure new findings into a more encompassing view of the genesis of degenerative diseases and may inspire novel approaches for their study and therapy.

Cancer is an increasingly common disease and is considered one of the main causes of death in the world. Lophocereus schottii ( L. schottii ) is a cactus used in Mexico in traditional medicine for cancer treatment. This study aimed to determine the effect of the ethanolic extract and the polar and nonpolar fractions of L. schottii in murine L5178Y lymphoma cells in vitro , analyzing their effect on the proliferative activity of splenocytes, and establishing the effective concentration 50 (EC 50 ) of the polar fraction. In addition, the secondary metabolites present in the extracts were determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The study establishes that the three extracts of L. schottii have a cytotoxic effect on L5178Y cells and on the splenocytes stimulated with ConA. Additionally, the polar fraction has a significantly greater effect being three times more effective than cyclophosphamide on inhibiting the viability of L5178Y cells. Secondary metabolites present are mainly flavonoids and alkaloids, but there are also some terpenoids and sterols. Ultimately, polar fraction can be considered an anticancer substance, since its EC 50 of 15 μg/mL is within the parameters established by the National Cancer Institute., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Orozco-Barocio, Robles-Rodríguez, Camacho-Corona, Méndez-López, Godínez-Rubí, Peregrina-Sandoval, Rivera, Rojas Mayorquín and Ortuno-Sahagun.)

Legumes are associated with gut health benefits, and increasing evidence indicates that their consumption reduces the risk of chronic diseases that include autoimmunity. Beans are rich sources of compounds with health-promoting effects, and recent metabolomic approaches have enabled the comprehensive characterization of the chemical composition of Vicia faba L. This article reviewed whether the phytocompounds in broad beans might modulate the aryl hydrocarbon receptor (AhR), which plays an essential role in autoantigen tolerance as a potential dietary strategy for autoimmune disease management. Therefore, thirty molecules present in Vicia faba of the chemical classes of flavonoids, chalcones, stilbenes, jasmonates, alkaloids, and amino acids, and either a human- or microbiome-derived product of biotransformation, retrieved from the literature or predicted in silico were evaluated by docking for affinity against the ligand-binding domain of AhR. Most analyzed compounds showed high affinity even after their metabolism which indicate that some AhR modulators remain active despite several steps in their biotransformation. Hence, our results suggest that in similitude with the gut metabolism of the tryptophan, phytocompounds mainly polyphenols also lead to metabolites that induce the AhR pathway. Furthermore, wyerone acid, wyerone epoxide, jasmonic acid, stizolamine, vicine, and convicine and their metabolite derivatives are reported for the first time as potential AhR ligands. Overall, chronic consumption of phytochemicals in Vicia faba L. and their gut biotransformation may protect against autoimmune disease pathogenesis by AhR modulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Méndez-López, Sosa de León, López-Cabanillas Lomelí, González-Martínez and Vázquez-Rodríguez.)

The bioassay-guided fractionation of a CHCl 3 -MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability ( p ≤ 0.05) by a WST-1 assay at a concentration of 100 μg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC 25 = 23 μg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated ( p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.

Cissus trifoliata (L.) L belongs to the Vitaceae family and is an important medicinal plant used in Mexico for the management of infectious diseases and tumors. The present study aimed to evaluate the metabolic profile of the stems of C. trifoliata and to correlate the results with their antibacterial and cytotoxic activities. The hexane extract was analyzed using gas chromatography coupled with mass spectrometry (GC-MS) and the CHCl 3 -MeOH and aqueous extracts by ultraperformance liquid chromatography quadrupole time of fly mass spectrometry (UPLC-QTOF-MS). The antibacterial activity was determined by broth microdilution and the cytotoxicity was evaluated using MTS cell proliferation assay. Forty-six metabolites were putatively identified from the three extracts. Overall, terpenes, flavonoids and stilbenes characterize the metabolic profile. No antibacterial activity was found in any extract against the fifteen bacteria strains tested (MIC >500 µg/mL). However, high cytotoxic activity (IC 50 ≤ 30 µg/mL) was found in the hexane and aqueous extracts against hepatocarcinoma and breast cancer cells (Hep3B, HepG2 and MCF7). This is the first report of the bioactive compounds of C. trifoliata stems and their antibacterial and cytotoxic properties. The metabolic profile rich in anticancer compounds correlate with the cytotoxic activity of the extracts from the stems of C. trifoliata . This study shows the antitumor effects of this plant used in the traditional medicine and justifies further research of its anticancer activity., Competing Interests: The authors declare no conflict of interest.

Background: Tumorigenic transformation of human epithelial cells in vitro has been described experimentally as the potential result of spontaneous immortalization. This process is characterized by a series of cell-state transitions, in which normal epithelial cells acquire first a senescent state which is later surpassed to attain a mesenchymal stem-like phenotype with a potentially tumorigenic behavior. In this paper we aim to provide a system-level mechanistic explanation to the emergence of these cell types, and to the time-ordered transition patterns that are common to neoplasias of epithelial origin. To this end, we first integrate published functional and well-curated molecular data of the components and interactions that have been found to be involved in such cell states and transitions into a network of 41 molecular components. We then reduce this initial network by removing simple mediators (i.e., linear pathways), and formalize the resulting regulatory core into logical rules that govern the dynamics of each of the network components as a function of the states of its regulators., Results: Computational dynamic analysis shows that our proposed Gene Regulatory Network model recovers exactly three attractors, each of them defined by a specific gene expression profile that corresponds to the epithelial, senescent, and mesenchymal stem-like cellular phenotypes, respectively. We show that although a mesenchymal stem-like state can be attained even under unperturbed physiological conditions, the likelihood of converging to this state is increased when pro-inflammatory conditions are simulated, providing a systems-level mechanistic explanation for the carcinogenic role of chronic inflammatory conditions observed in the clinic. We also found that the regulatory core yields an epigenetic landscape that restricts temporal patterns of progression between the steady states, such that recovered patterns resemble the time-ordered transitions observed during the spontaneous immortalization of epithelial cells, both in vivo and in vitro., Conclusion: Our study strongly suggests that the in vitro tumorigenic transformation of epithelial cells, which strongly correlates with the patterns observed during the pathological progression of epithelial carcinogenesis in vivo, emerges from underlying regulatory networks involved in epithelial trans-differentiation during development.

Introduction: The hormone leptin, which is produced in the adipose tissue, may influence tumorigenesis directly via its receptor (Ob-R). Thus, a role for Ob-R in endometrial carcinogenesis has been proposed. However, most studies neither included samples of the entire histological progression of endometrial carcinoma nor examined Ob-R jointly with the estrogen and progesterone receptors (ER and PR, respectively)., Material and Methods: To determine the fluctuations of Ob-R, ER, and PR during the histological progression of endometrial carcinoma, we assessed their expression via immunohistochemistry (IHC) in six histological types of endometrium (proliferative, secretory, nonatypical and atypical hyperplasia, and endometrioid and nonendometrioid endometrial carcinoma), in which we performed histopathological and digital scoring for the quantification of receptors., Results: We found that Ob-R expression was positively correlated with that of ER and PR ( r = 1, p < 0.001; r = 0.943, p < 0.005, respectively), and there was a significant difference in Ob-R expression among proliferative normal endometrium, hyperplasias, and carcinomas, according to their relative digitally scored Ob-R expression ( p < 0.001). In addition, we observed that Ob-R expression in the secretory endometrium was more similar to that of carcinomas than to its proliferative counterpart., Conclusions: These results indicate that Ob-R expression fluctuates during endometrial carcinogenesis in correlation with ER and PR, suggesting that Ob-R expression in vivo is highly dependent on estrogen and progesterone activities in the endometrium and on its ER and PR status, as suggested previously by in vitro studies., Competing Interests: The authors declare no conflict of interest.

The concentrations of recognized or suspected genotoxic and carcinogenic agents found in the air of large cities and, in particular, developing countries, have raised concerns about the potential for chronic health effects in the populations exposed to them. The biomonitoring of environmental genotoxicity requires the selection of representative organisms as "sentinels," as well as the development of suitable and sensitive assays, such as those aimed at assessing DNA damage. The aim of this study was to evaluate DNA damage levels in erythrocytes from Columba livia living in the metropolitan area of Monterrey, Mexico, compared with control animals via comet assay, and to confirm the results via Micronuclei test (MN) and DNA breakage detection-fluorescence in situ hybridization (DBD-FISH). Our results showed a significant increase in DNA migration in animals from the area assayed compared with that observed in control animals sampled in non-contaminated areas. These results were confirmed by MN test and DBD-FISH. In conclusion, these observations confirm that the examination of erythrocytes from Columba livia via alkaline comet assay provides a sensitive and reliable end point for the detection of environmental genotoxicants.

The adipokine leptin plays a critical role in the regulation of reproductive function and there has been growing interest in its potential role in the development of cancers in which obesity is an established risk factor. Serum leptin levels were found to be higher in patients diagnosed with endometrial and ovarian cancer compared to those observed in healthy individuals. This study was conducted to determine the expression of the leptin receptor (Ob-R) in endometrial biopsies of patients diagnosed with endometrial and ovarian cancer. In this preliminary study, immunohistochemistry (IHC) and the color deconvolution method were used to assess the expression levels of the Ob-R protein in three groups of endometrial tissue: one from patients diagnosed with endometrioid endometrial carcinoma, one from patients diagnosed with ovarian cancer and one from individuals without any diagnosed gynecologic disease (control group). Our results demonstrated that the highest expression of Ob-R protein in endometrial biopsies was detected in the ovarian cancer group (P=0.000). This finding suggests that changes in Ob-R expression may be assessed through the measurement of the optical density of endometrial biopsies and may become a useful tool in preventive screening, particularly for ovarian cancer.

Background and Aims: We undertook this study to compare the expression level of prostate apoptosis response-4 (Par-4) among patient outcome in two groups of women with breast cancer (short and long survival) and two groups without breast cancer (benign lesion and control)., Methods: We included breast specimens with nonhistological abnormalities (eight samples) as a control group. Semiquantitative and quantitative analysis of immunohistochemical staining by image analysis software were used to study the intensity of Par-4 expression. Both methods produced similar results (p>0.05)., Results: No significant expression of Par-4 was observed in normal breast tissue. Benign lesions and breast cancer tissue showed strong nuclear expression of Par-4, predominantly on epithelial cells and specifically in ductal cells. Par-4 expression was lower in myoepithelial cells and there was no appreciable stromal staining. Significantly less Par-4 reactivity was detected in tissue from patients with a short survival compared with patients with benign lesions and those with a long survival., Conclusions: Our findings suggest that a lower expression level of Par-4 is related to an unfavorable prognosis. A larger prospective study of samples of all patient groups with a longer follow-up is needed to validate this finding., (Copyright 2010 IMSS. Published by Elsevier Inc. All rights reserved.)