IFN-γ stimulates Paneth cell secretion through necroptosis mTORC1 dependent.

Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-γ a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown.

Synergistic effect of antagonists to KRas4B/PDE6 molecular complex in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among all human cancers as it is highly resistant to chemotherapy. K-Ras mutations usually trigger the development and progression of PDAC. We hypothesized that compounds stabilizing the KRas4B/PDE6δ complex could serve as PDAC treatments.

The mRNA and protein levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence, and risk of death in cervical cancer patients.

Introduction: Patients with cervical cancer (CC) may experience local recurrence very often after treatment; when only clinical parameters are used, most cases are diagnosed in late stages, which decreases the chance of recovery. Molecular markers can improve the prediction of clinical outcome. Glycolysis is altered in 70% of CCs, so molecular markers of this pathway associated with the aggressiveness of CC can be identified.

Rictor/Mammalian Target of Rapamycin Complex 2 Signaling Protects Colonocytes from Apoptosis and Prevents Epithelial Barrier Breakdown.

Epithelial barrier impairment is a hallmark of several pathologic processes in the gut, including inflammatory bowel diseases. Several intracellular signals prevent apoptosis in intestinal epithelial cells. Herein, we show that in colonocytes, rictor/mammalian target of rapamycin complex 2 (mTORC2) signaling is a prosurvival stimulus.

H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable and devastating malignant tumors. Epigenetic modifications such as DNA methylation and histone modification regulate tumor initiation and progression. However, the contribution of histone variants in PDAC is unknown.

Dengue Virus Serotype 2 and Its Non-Structural Proteins 2A and 2B Activate NLRP3 Inflammasome.

Dengue is the most prevalent and rapidly transmitted mosquito-borne viral disease of humans. One of the fundamental innate immune responses to viral infections includes the processing and release of pro-inflammatory cytokines such as interleukin (IL-1β and IL-18) through the activation of inflammasome. Dengue virus stimulates the Nod-like receptor (NLRP3-specific inflammasome), however, the specific mechanism(s) by which dengue virus activates the NLRP3 inflammasome is unknown.

A Model for the Homotypic Interaction between Na,K-ATPase β Subunits Reveals the Role of Extracellular Residues 221-229 in Its Ig-Like Domain.

The Na, K-ATPase transports Na and K across the membrane of all animal cells. In addition to its ion transporting function, the Na, K-ATPase acts as a homotypic epithelial cell adhesion molecule via its β subunit. The extracellular region of the Na, K-ATPase β subunit includes a single globular immunoglobulin-like domain.

Curcumin induces p53-independent inactivation of Nrf2 during oxidative stress-induced apoptosis.

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is a master regulator of a battery of antioxidant and detoxificant genes with cytoprotective function. Since Nrf2 inactivation is necessary for the complete execution of apoptosis in the presence of extensive cellular damage caused by oxidative stress, constant activation of Nrf2 may protect tumoral cells from apoptosis. The tumor suppressor gene p53 has been suggested to participate in apoptosis-related repression of Nrf2.

New insights into radioresistance in breast cancer identify a dual function of miR-122 as a tumor suppressor and oncomiR.

Radioresistance of tumor cells gives rise to local recurrence and disease progression in many patients. MicroRNAs (miRNAs) are master regulators of gene expression that control oncogenic pathways to modulate the radiotherapy response of cells. In the present study, differential expression profiling assays identified 16 deregulated miRNAs in acquired radioresistant breast cancer cells, of which miR-122 was observed to be up-regulated.

Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages.

Intestinal macrophages are highly mobile cells with extraordinary plasticity and actively contribute to cytokine-mediated epithelial cell damage. The mechanisms triggering macrophage polarization into a proinflammatory phenotype are unknown. Here, we report that during inflammation macrophages enhance its intercellular adhesion properties in order to acquire a M1-phenotype.

Compartmentalized Response of IL-6/STAT3 Signaling in the Colonic Mucosa Mediates Colitis Development.

A single layer of polarized epithelial cells lining the colonic mucosa create a semipermeable barrier indispensable for gut homeostasis. The role of intestinal epithelial cell (IEC) polarization in the maintenance of the epithelial homeostasis and in the development of inflammatory bowel diseases is not fully understood. In this review, now we report that IEC polarization plays an essential role in the regulation of IL-6/STAT3 signaling in the colonic mucosa.

The feline calicivirus leader of the capsid protein causes survivin and XIAP downregulation and apoptosis.

Calicivirus infection causes intrinsic apoptosis, leading to viral propagation in the host. During murine norovirus infection, a reduction in the anti-apoptotic protein survivin has been documented. Here we report that in feline calicivirus infection, a downregulation of the anti-apoptotic proteins survivin and XIAP occur, which correlates with the translocation of the pro-apoptotic protein Smac/DIABLO from the mitochondria to the cytoplasm and the activation of caspase-3.

mTORC1 Prevents Epithelial Damage During Inflammation and Inhibits Colitis-Associated Colorectal Cancer Development.

Epithelial cells lining the intestinal mucosa constitute a selective-semipermeable barrier acting as first line of defense in the organism. The number of those cells remains constant during physiological conditions, but disruption of epithelial cell homeostasis has been observed in several pathologies. During colitis, epithelial cell proliferation decreases and cell death augments.

Postsplicing-Derived Full-Length Intron Circles in the Protozoan Parasite .

Noncoding circular RNAs are widespread in the tree of life. Particularly, intron-containing circular RNAs which apparently upregulate their parental gene expression. , the causative agent of dysentery and liver abscesses in humans, codes for several noncoding RNAs, including circular ribosomal RNAs, but no intron containing circular RNAs have been described to date.

Competitive suppression of dengue virus replication occurs in chikungunya and dengue co-infected Mexican infants.

Background: Co-circulation of dengue virus (DENV) and chikungunya virus (CHIKV) is increasing worldwide but information on the viral dynamics and immune response to DENV-CHIKV co-infection, particularly in young infants, is scant.

Methods: Blood samples were collected from 24 patients, aged 2 months to 82 years, during a CHIKV outbreak in Mexico. DENV and CHIKV were identified by RT-PCR; ELISA was used to detect IgM and IgG antibodies.

Curcumin differentially affects cell cycle and cell death in acute and chronic myeloid leukemia cells.

Curcumin is a phytochemical with potent anti-neoplastic properties. The antitumoral effects of curcumin in cells derived from chronic or acute myeloid leukemia have been already described. However, a comparative study of the cytostatic and cytotoxic effects of curcumin on chronic and acute myeloid leukemia cells has not yet been performed.

C33-A cells transfected with E6*I or E6*II the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis.

The HPV-16 E6/E7 bicistronic immature transcript produces 4 mature RNAs: the unspliced HPV-16 E6/E7 product and 3 alternatively spliced mRNAs. The 3 spliced mRNAs encode short forms of the E6 oncoprotein, namely E6*I, E6*II and E6^E7. In this study we showed that transfection of C-33A cells with monocistronic constructs of these cDNAs fused to GFP, produced different effects on apoptosis, after the treatment with cisplatin.

pVHL suppresses Akt/β-catenin-mediated cell proliferation by inhibiting 14-3-3ζ expression.

The mechanisms controlling degradation of cytosolic β-catenin are important for regulating β-catenin co-transcriptional activity. Loss of von Hippel-Lindau protein (pVHL) has been shown to stabilize β-catenin, increasing β-catenin transactivation and β-catenin-mediated cell proliferation. However, the role of phosphoinositide 3-kinase (PI3K)/Akt in the regulation of β-catenin signaling downstream from pVHL has never been addressed.

Tumor suppressor miR-29c regulates radioresistance in lung cancer cells.

Radiotherapy is an important treatment option for non-small cell lung carcinoma patients. Despite the appropriate use of radiotherapy, radioresistance is a biological behavior of cancer cells that limits the efficacy of this treatment. Deregulation of microRNAs contributes to the molecular mechanism underlying resistance to radiotherapy in cancer cells.

Different Association of Human Papillomavirus 16 Variants with Early and Late Presentation of Cervical Cancer.

The median age of cervical cancer (CC) presentation coincides with the mean age of menopause presentation (49 years) in Mexico. Here, we investigated the association between different HPV16 variants and early (≤ 49 years) or delayed (≥ 50 years) CC presentation. We conducted a case-case study that included 462 CCs, 386 squamous cell carcinomas (SCC), 63 adenocarcinomas (ACC), and 13 additional cell types.

A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe.

Curcumin is extensively investigated as a good chemo-preventive agent in the development of many cancers and particularly in leukemia, including treatment of chronic myelogenous leukemia and it has been proposed as an adjuvant for leukemia therapies. Human chronic myeloid leukemia cells (K562), were treated with 20 μM of curcumin, and we found that a subpopulation of these cells were arrested and accumulate in the G2/M phase of the cell cycle. Characterization of this cell subpopulation showed that the arrested cells presented nuclear morphology changes resembling those described for mitotic catastrophe.

The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium.

The gastrointestinal tract is the largest hormone-producing organ in the body due to a specialized cell population called enteroendocrine cells (EECs). The number of EECs increases in the mucosa of inflammatory bowel disease patients; however, the mechanisms responsible for these changes remain unknown. Here, we show that the pro-inflammatory cytokines interferon γ (IFNγ) and tumor necrosis factor α (TNFα) or dextran sulfate sodium (DSS)-induced colitis increase the number of EECs producing chromogranin A (CgA) in the colonic mucosa of C57BL/6J mice.

Tyrosine phosphorylation/dephosphorylation of myosin II essential light chains of Entamoeba histolytica trophozoites regulates their motility.

Entamoeba histolytica trophozoites dwell in the human intestine as comensals although under still unclear circumstances become invasive and destroy the host tissues. For these activities, trophozoites relay on remarkable motility provided by the cytoskeleton organization. Amebic actin and some of its actin-associated proteins are well known, while components of the myosin II molecule, although predicted from the E.

Resveratrol inhibits cell cycle progression by targeting Aurora kinase A and Polo-like kinase 1 in breast cancer cells.

The Aurora protein kinase (AURKA) and the Polo-like kinase-1 (PLK1) activate the cell cycle, and they are considered promising druggable targets in cancer therapy. However, resistance to chemotherapy and to specific small‑molecule inhibitors is common in cancer patients; thus alternative therapeutic approaches are needed to overcome clinical resistance. Here, we showed that the dietary compound resveratrol suppressed the cell cycle by targeting AURKA and PLK1 kinases.