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Physical changes in the tumor microenvironment, such as increased stiffness, regulate cancer hallmarks and play an essential role in gene expression, cell morphology, migration, and malignancy. However, the response of cancer cells to stiffness is not homogeneous and varies depending on the cell type and its mechanosensitivity. In this study, we investigated the differential responses of cervical (HeLa) and prostate (PC-3) cancer cell lines, as well as non-tumoral cell lines (HEK293 and HPrEC), to stiffness using polyacrylamide hydrogels mimicking normal and tumoral tissues. We analyzed cell morphology, migration, and the expression of neuropilin 1 (NRP1), a receptor involved in angiogenesis, cell migration, and extracellular matrix remodeling, known to be associated with cancer progression and poor prognosis. Our findings reveal that NRP1 expression increases on substrates mimicking the high stiffness characteristic of tumoral tissue in the non-tumoral cell lines HPrEC and HEK293. Conversely, in tumoral PC-3 cells, stiffness resembling normal prostate tissue induces an earlier and more sustained expression of NRP1. Furthermore, we observed that stiffness influences cell spreading, pseudopodia formation, and the mode of cell protrusion during migration. Soft substrates predominantly trigger bleb cell protrusion, while pseudopodia protrusions increase on substrates mimicking normal and tumor-like stiffnesses in HPrEC cells compared to PC-3 cells. Stiffer substrates also enhance the percentage of migratory cells, as well as their velocity and total displacement, in both non-tumoral and tumoral prostate cells. However, they only improve the persistence of migration in tumoral PC-3 cells. Moreover, we found that NRP1 co-localizes with actin, and its suppression impairs tumoral PC-3 spreading while decreasing pseudopodia protrusion mode. Our results suggest that the modulation of NRP1 expression by the stiffness can be a feedback loop to promote malignancy in non-tumoral and cancer cells, contingent upon the mechanosensitivity of the cells. [ABSTRACT FROM AUTHOR]

Period circadian regulator (Per)1 and Per2 genes are involved in the molecular mechanism of the circadian clock, and exhibit tumor suppressor properties. Several studies have reported a decreased expression of Per1, Per2 and Per3 genes in different types of cancer and cancer cell lines. Promoter methylation downregulates Per1, Per2 or Per3 expression in myeloid leukemia, breast, lung, and other cancer cells; whereas histone deacetylase inhibitors (HDACi) upregulate Per1 or Per3 expression in certain cancer cell lines. However, the transcriptional regulation of Per1 and Per2 in cancer cells by chromatin modifications is not fully understood. The present study aimed to determine whether HDACi regulate Per1 and Per2 expression in gastric cancer cell lines, and to investigate changes in chromatin modifications in response to HDACi. Treatment of KATO III and NCI-N87 human gastric cancer cells with sodium butyrate (NaB) or Trichostatin A (TSA) induced Per1 and Per2 mRNA expression in a dose-dependent manner. Chromatin immunoprecipitaion assays revealed that NaB and TSA decreased lysine 9 trimethylation on histone H3 (H3K9me3) at the Per1 promoter. TSA, but not NaB increased H3K9 acetylation at the Per2 promoter. It was also observed that binding of Sp1 and Sp3 to the Per1 promoter decreased following NaB treatment, whereas Sp1 binding increased at the Per2 promoter of NaB- and TSA-treated cells. In addition, Per1 promoter is not methylated in KATO III cells, while Per2 promoter was methylated, although NaB, TSA, and 5-Azacytidine do not change the methylated CpGs analyzed. In conclusion, HDACi induce Per1 and Per2 expression, in part, through mechanisms involving chromatin remodeling at the proximal promoter of these genes; however, other indirect mechanisms triggered by these HDACi cannot be ruled out. These findings reveal a previously unappreciated regulatory pathway between silencing of Per1 gene by H3K9me3 and upregulation of Per2 by HDACi in cancer cells. [ABSTRACT FROM AUTHOR]

Dietary tannins can affect protein digestion and absorption, be toxic, and influence food selection by being astringent and bitter tasting. Animals that usually ingest tannins may regularly secrete tannin‐binding salivary proteins (TBSPs) to counteract the negative effects of tannins or TBSPs production can be induced by a tannin‐rich diet. In the wild, many primates regularly eat a diet that contains tannin‐rich leaves and unripe fruit and it has been speculated that they have the physiological ability to cope with dietary tannins; however, details of their strategy remains unclear. Our research details the salivary protein composition of wild and zoo‐living black howler monkeys (Alouatta pigra) feeding on natural versus manufactured low‐tannin diets, and examines differences in TBSPs, mainly proline‐rich proteins (PRPs), to determine whether production of these proteins is dependent on the tannin content of their food. We measured the pH, flow rate, and concentration of total protein and trichloroacetic acid soluble proteins (an index of PRPs) in saliva. Howler monkeys produced slightly alkaline saliva that may aid in the binding interaction between tannin and salivary proteins. We used gel electrophoresis to describe the salivary protein profile and this analysis along with a tannin‐binding assay allowed us to detect several TBSPs in all individuals. We found no differences in the characteristics of saliva between wild and zoo‐living monkeys. Our results suggest that black howler monkeys always secrete TBSPs even when fed on foods low in tannins. This strategy of constantly using this salivary anti‐tannin defense enables them to obtain nutrients from plants that sometimes contain high levels of tannins and may help immediately to overcome the astringent sensation of their food allowing howler monkeys to eat tanniferous plants. [ABSTRACT FROM AUTHOR]

Saliva is a fluid that can be collected easily and noninvasively. Its functions in the oral cavity are well known. Advances in molecular biology and technology, as well as research conducted by the various disciplines of omics (genomics, transcriptomics, proteomics, metabolomics, and metagenomics) have contributed to the identification and characterization of salivary components, including DNA, RNA, proteins, metabolites, and microorganisms. These biomolecules enter the saliva through extracellular and intracellular routes, providing information from several organs and systems and raising the possibility of their use as disease biomarkers. In recent years, these factors have expanded the potential use of saliva as a diagnostic fluid for oral and systemic diseases. This review integrates information regarding salivary biomolecules studied through omics and explores their utility as biomarkers for the diagnosis of several infectious and noninfectious diseases, and the opportunity they represent for the development of point of care devices for clinical application. We also discuss the advantages, disadvantages, and challenges to be overcome in order to establish saliva as a useful fluid for the accurate diagnosis and monitoring of a wide range of diseases. [ABSTRACT FROM AUTHOR]

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• Glutathione S-transferase Mu1 or Theta1 absence increases the risk of oral clefts. • Null Glutathione S-transferase Theta1 showed a higher risk for oral clefts. • Maternal null Glutathione S-transferase Theta1 showed a higher risk than infant. • Infant null Glutathione S-transferase Mu1 showed a higher risk than maternal. • Maternal frequent exposure to passive smoking increases the risk of oral clefts. To investigate whether null variants of Glutathione S-transferase Mu 1 (GSTM1) and GST Theta 1 (GSTT1) in infants and mothers, as well as maternal exposures to environmental factors, contribute to the risk of non-syndromic cleft lip with or without palate (NSCL/P) in a Mexican population. We performed a matched pair case-control study, including 98 cases and 98 controls and their mothers. Sociodemographic information and environmental exposures were collected by a questionnaire. Null variants of GSTM1 and GSTT1 were assessed by multiplex Polymerase Chain Reaction (PCR). Odds ratios (OR) and their 95 % confidence intervals (CI) were calculated to estimate risks. The interaction of genetic variables with smoking and adjusted ORs were evaluated by binary logistic regression. Homozygous null GSTM1 was associated with the risk of NSCL/P when present in mothers (OR = 2.45, 95 % CI 1.23–4.86) or infants (OR = 2.98, 95 % CI 1.45–6.14). A higher risk was also found when children carried the homozygous null GSTT1 (OR = 4.89, 95 % CI 2.42–9.87). In mothers, this variant showed a crude risk of 9.17 (95 % CI 3.95–21.29), which increased to OR = 13.81 (95 % CI 1.63–117.09) upon interaction with frequent passive smoking (5–7 days/week). Sociodemographic and other environmental exposures were not significantly associated with the risk of NSCL/P. Maternal and infant GSTT1 and GSTM1 homozygous null genotypes were associated with a higher risk of NSCL/P, and the results suggest an interaction of the maternal GSTT1-null/null genotype with frequent passive smoking. [ABSTRACT FROM AUTHOR]

• GFAP expression was analyzed in the olfactory bulb of food entrained rabbit pups. • GFAP protein levels change in synchrony with feeding time. • Morphology of GFAP+ radial glia processes changes with a daily rhythm. • Locomotor and neuronal activity rhythms are in anti-phase with the expression of GFAP. When food is restricted daily to a fixed time, animals show uncoupled molecular, physiological and behavioral circadian rhythms from those entrained by light and controlled by the suprachiasmatic nucleus. The loci of the food-entrainable oscillator and the mechanisms by which rhythms emerge are unclear. Using animals entrained to the light-dark cycle, recent studies indicate that astrocytes in the suprachiasmatic nucleus play a key role in the regulation of circadian rhythms. However, it is unknown whether astrocytic cells can be synchronized by circadian restricted feeding. Studying the olfactory bulb (OB) of rabbit pups entrained to daily feeding, we hypothesized that the expression of glial fibrillary acidic protein (GFAP) and the morphology of GFAP-immunopositive cells change in synchrony with timing of feeding. By using pups fed at 1000 h or 2200 h, we found that GFAP protein expression in the OB changes with a nadir at feeding time and a peak 16 h after feeding. We also found that length of radial glia processes, the most abundant GFAP+ cell in the rabbit pup OB, shows a daily change also coupled to feeding time. These temporal changes of GFAP were expressed in anti-phase to the rhythms of locomotor activity and c-Fos immunoreactivity. The results indicate that GFAP expression and elongation-retraction of radial glia processes are coupled by feeding time and suggest that glia cells may play an important functional role in food entraining of the OB circadian oscillator. [ABSTRACT FROM AUTHOR]

• SERCA3 mRNA expression is decreased in hepatocelullar carcinoma cells (HCC). • NaB and TSA up-regulate SERCA3 mRNA expression in rat HCC. • NaB and TSA increase H3K9 and H3K27 acetylation at the ATP2A3 promoter. • TSA increases occupancy of p300, which mediates H3K9 acetylation at the ATP2A3 promoter. • Inhibition of p300 decreases basal and TSA-mediated SERCA3 mRNA expression. Sarco(endo)plasmic reticulum Ca2+-ATPases (SERCA) expression is reduced or absent in several types of cancer and cancer cell lines; however, their expression and regulation in hepatocellular carcinoma (HCC) are unknown. Histone deacetylase inhibitors (HDACi) increase SERCA3 mRNA expression in gastric and breast cancer cell lines by increasing H3K9ac and binding of Sp1 and Sp3 transcription factors to the promoter; however, the molecular mechanism is not fully understood. Our results show that ATP2A3 (SERCA3) gene expression is decreased in human HCC samples and rat HCC AS-30D cells compared to normal liver, and HCC patients with high expression of ATP2A3 had longer overall survival than those with low expression. Sodium butyrate (NaB) and trichostatin A (TSA) increase SERCA3 mRNA expression in AS-30D cells, whereas SERCA2b mRNA expression did not change. NaB and TSA increase H3K9ac and H3K27ac in two ATP2A3 promoter regions. Besides, NaB treated cells increased Sp1 and Sp3 occupancy at ATP2A3 promoter; whereas TSA treated cells showed increased p300 levels at ATP2A3 promoter. Inhibition of p300 by C646, a specific inhibitor, mitigates SERCA3 mRNA induction by TSA, and reduces more than 70% of basal SERCA3 mRNA expression, suggesting that p300 is important for ATP2A3 gene transcription in AS-30D cells. Moreover, inhibition of p300 decreases H3K9ac in TSA treated cells. Our results provide evidence of decreased SERCA3 expression in human HCC samples and rat AS-30D cells and a correlation of SERCA3 expression with overall survival in HCC patients. Also, reveal new insights in SERCA3 transcriptional regulation mediated by HDACi. [ABSTRACT FROM AUTHOR]

Intact pks15 / 1 is involved in the biosynthesis of phenolic glycolipids and proposed as a marker for virulence and phylogeny in tuberculosis. Identification of intact condition is achieved mainly by DNA sequencing. For this reason the aim of this study was to develop a reproducible endpoint PCR-assay to characterize it. [ABSTRACT FROM AUTHOR]

The contribution of Interleukin-1β (IL-1β) to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. The goal of this study was to determine the hippocampal expression of IL-1β and its type 1 receptor (IL-1RI) following SE induced by the lithium-pilocarpine model in fourteen-days-old rat pups; control animals were given an equal volume of saline instead of the convulsant. IL-1β and IL-1RI mRNA hippocampal levels were assessed by qRT-PCR 6 and 24 h after SE or control conditions. IL-1β and IL-1RI expression was detected in the dorsal hippocampus by immunohistochemical procedures; Fluoro-Jade B staining was carried out in parallel sections in order to detect neuronal cell death. IL-1β mRNA expression was increased 6 h following SE, but not at 24 h; however IL-1RI mRNA expression was unaffected when comparing with the control group. IL-1β and IL-1RI immunoreactivity was not detected in control animals. IL-1β and IL-1RI were expressed in the CA1 pyramidal layer, the dentate gyrus granular layer and the hilus 6 h after SE, whereas injured cells were detected 24 h following seizures. Early expression of IL-1β and IL-1RI in the hippocampus could be associated with SE-induced neuronal cell death mechanisms in the developing rat.