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This study aimed to evaluate the timing and frequency of spontaneous apneas during breathing and swallowing by using cineradiography on mouse models of early/initial or late/advanced Parkinson's disease (PD). C57BL/6 J mice received either 6-OHDA or vehicle injections into their right striatum, followed by respiratory movement recordings during spontaneous breathing and swallowing, and a stress challenge, two weeks later. Experimental group animals showed a significantly lower respiratory rate (158.66 ± 32.88 breaths/minute in late PD, 173.16 ± 25.19 in early PD versus 185.27 ± 25.36 in controls; p<0.001) and a significantly higher frequency of apneas (median 1 apnea/minute in both groups versus 0 in controls; p<0.001). Other changes included reduced food intake and the absence of swallow apneas in experimental mice. 6-OHDA-induced nigrostriatal degeneration in mice disrupted respiratory control, swallowing, stress responsiveness, and feeding behaviors, potentially hindering airway protection and elevating the risk of aspiration., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Salivary alpha-amylase (sAA) is an enzyme found in saliva and is considered a noninvasive biomarker for sympathetic nervous system activity. While a wide range of sAA activity in response to stress has been reported in nonhuman primates, the effects of stress on sAA activity in common marmosets are still unknown. We tested the hypothesis that advanced age and cognitive function may have an impact on stress-related sAA reactivity in marmosets. Thirteen marmosets (nine males and five females) had saliva samples collected during a stressful condition (manual restraint stress) at two different time points, with a 60-min interval. On the next day, the animals underwent the object recognition test (ORT, a type of cognitive test), and then oral examinations. The animals were categorized into two age groups: old (10-13 years), and very old (15-22 years). Irrespective of age, sAA levels showed a significant difference between T1 (mean 2.07 ± 0.86 U/mL) and T2 samples (mean 1.03 ± 0.67 U/mL), with higher values observed at T1 (p < 0.001). The intra-assay coefficients of variation (CV) for low and high sAA concentrations were 10.79% and 8.17%, respectively, while the interassay CVs for low and high sAA concentrations were 6.39% and 4.38%, respectively. Oral health issues were common but did not significantly impact sAA levels. The ORT indicated that the animals could recognize an object placed in the cage 6 h after familiarization. In conclusion, all marmosets showed a higher sAA concentration in the first saliva sample as compared to the second saliva sample collected 1 h later, indicating adaptation to stress. No significant differences in sAA levels were observed between sexes, ORT performance, or oral health. Our results indicate that autonomic responsivity and cognitive (memory) functions were preserved even in very old marmosets., (© 2024 Wiley Periodicals LLC.)

Background: Considering that microRNAs (miRNAs), extracellular vesicles and particles (EVPs) and the amyloid precursor protein (APP) processing have been shown to be altered in oral squamous cells carcinoma (OSCC), it is possible that miRNAs that target APP processing pathways in EVPs are impacted in tumor cells. Our aim was to evaluate miRNAs that target APP itself or disintegrin and metalloproteinase domain 10 (ADAM10), which generate a trophic compound, sAPPα, in EVPs derived from OSCC cell lines, an aggressive and non-invasive, compared to normal keratinocytes., Methods: We used two OSCC cell lines, an aggressive human oral squamous cell carcinoma cell line (SCC09) and a less aggressive cell line (CAL27) compared with a keratinocyte lineage (HaCaT). Cells were maintained in cell media, from which we isolated EVPs. EVPs were evaluated regarding their size and concentration using Nanotracking Analysis. We measured the levels of miRNAs which had as potential downstream target APP or ADAM10, specifically miR-20a-5p, miR-103a-3p, miR-424-5p, miR-92b-3p, miR-31-5p, and miR-93-5., Results: There were no differences on size distributions and concentration of isolated EVPs. OSCC cell lines-derived EVPs miR-20a-5p, miR-92b-3p, and miR-93-5p were upregulated in comparison to HaCaT-derived EVPs; while miR-31-5p was reduced in EVPs obtained from CAL27 cells., Conclusion: Our results indicate changes in miRNAs that target APP machinery processing in EVPs derived from OSCC cell lines of different aggressiveness, which may be involved with abnormal miRNA expression in OSCC tissue and/or releasing tumor suppressor miRNA., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Matrix stiffening is ubiquitous in solid tumors and can direct epithelial-mesenchymal transition (EMT) and cancer cell migration. Stiffened niche can even cause poorly invasive oral squamous cell carcinoma (OSCC) cell lines to acquire a less adherent, more migratory phenotype, but mechanisms and durability of this acquired "mechanical memory" are unclear. Here, we observed that contractility and its downstream signals could underlie memory acquisition; invasive SSC25 cells overexpress myosin II (vs. noninvasive Cal27 cells) consistent with OSCC. However, prolonged exposure of Cal27 cells to a stiff niche or contractile agonists up-regulated myosin and EMT markers and enabled them to migrate as fast as SCC25 cells, which persisted even when the niche softened and indicated "memory" of their prior niche. Stiffness-mediated mesenchymal phenotype acquisition required AKT signaling and was also observed in patient samples, whereas phenotype recall on soft substrates required focal adhesion kinase (FAK) activity. Phenotype durability was further observed in transcriptomic differences between preconditioned Cal27 cells cultured without or with FAK or AKT antagonists, and such transcriptional differences corresponded to discrepant patient outcomes. These data suggest that mechanical memory, mediated by contractility via distinct kinase signaling, may be necessary for OSCC to disseminate.

Background: Imidazolium salts (IS), ionic derivatives of neutral imidazoles, have properties that can be adjusted by structural modifications to their cations and anions, which makes this particular class of compounds a promising option for developing biologically active compounds. The anti-tumor effects of the IS 1-n-butyl-3-methylimidazolium chloride (C 4 MImCl), 1-n-decyl-3-methylimidazolium chloride (C 10 MImCl), 1-n-hexadecyl-3-methylimidazolium chloride (C 16 MImCl), 1-n-hexadecyl-2,3-dimethylimidazolium chloride (C 16 M 2 ImCl), 1-n-octadecyl-3-methylimidazolium chloride (C 18 MImCl), 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C 16 MImMeS), and 1-n-hexadecyl-2,3- dimethylimidazolium methanesulfonate (C 16 M 2 ImMeS) on oral squamous cell carcinoma (OSCC) have been studied here., Methods: Oral squamous cell carcinoma cells (CAL27) were incubated with increasing IS doses and then submitted to proliferation (2D), cell death (2D) and spheroid assay (3D)., Results: The IS anti-tumor effect was dependent on both its N-alkyl chain length and anion, whereby C 16 MImCl proved to be more effective in combination for inhibiting cell proliferation and cell-cell adhesion, outperforming the methylated C 16 M 2 ImCl derivative and, most importantly, the gold standard-cisplatin. In addition, C 16 MImCl had little effect on keratinocytes and more pronounced effects on more aggressive tumor cells. It also exhibited similar effects on inducing cell death when compared to Cisplatin. This compound spread to a greater area of the tumor sphere and produced an enhanced number of apoptotic and necrotic cells in the tumor cell line, demonstrating only a small rise in the healthy cells., Conclusion: These data indicate that the effect of C 16 MlmCl on OSCC is promising, as it is selective for cancer cells., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Flavonoids have been proposed as potential chemotherapeutic agents because they are toxic against cancer cells but not harmful to healthy cells. This systematic review analyzed flavonoid effectiveness in human cancer chemotherapy. Overall, 22 phase II and 1 phase III clinical trials (PubMed, Scopus, and Web of Science) that used flavonoids as a single agent or combined with other therapeutics against hematopoietic/lymphoid or solid cancer published by January 2019 were selected for analysis. Flavopiridol was the most commonly used flavonoid (at a dose of 50-mg/m 2 IV) for all tumor types. Aside from the relatively low rate of complete response (CR) or partial response (PR) with any administration protocol, flavonoids showed higher positive outcomes for hematopoietic and lymphoid tissues (140 patients with CR and 88 with PR among 615 patients in 11 trials) than for solid tumors (4 patients with CR and 21 with PR among 525 patients in 12 trials). However, because of the high variety in administration schedule, more studies are needed to further understand how flavonoids can promote positive outcomes for cancer patients., (© 2019 John Wiley & Sons, Ltd.)

Parkinson's disease (PD) is known to cause tremor and rigidity, but other symptoms such as respiratory and autonomic dysfunctions are a major cause of disability and mortality in patients. In this study, we examined respiratory movements by using cineradiography on a murine model of late/advanced PD. Under surgical anesthesia, C57BL/6J mice received an injection of either 6-OHDA or vehicle solution to the right striatum. Two weeks after surgery, the animals had their respiratory movements recorded by video X-ray without any restraint. During recordings the animals were submitted to a mild acute-stress challenge. Behavioral tests were performed to assess the severity of the 6-OHDA lesion. As a result, behavioral tests confirmed severe motor impairments in 6-OHDA mice as compared to controls. 6-OHDA mice showed a predominantly thoracic respiratory pattern with reduced diaphragmatic excursion, and reduced respiratory frequency after stress. These results suggest that advanced nigrostrial degeneration may cause respiratory alterations with the features of obstructive-type respiratory disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell-cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 μM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 μM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 μM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell-cell adhesion, especially on tumor-derived spheroids. Also, in a xenograft model with patient-derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system known to cause a typical pattern of motor symptoms. In its later stages, PD is known to cause respiratory alterations including shortening of operational volumes and reduced velocity of respiratory-muscle contraction. It has been proposed that such changes are secondary to changes in posture and osteoarticular degeneration, leading to an alteration in the spinal axis that in turn could affect breathing mechanics. In this study, we examined respiratory movements by using cineradiography on a murine (C57BL/6J) model of mild hemi-PD. Under surgical anesthesia, PD mice received an injection of 6-OHDA solution to the right striatum, and were compared to control mice, which received an injection of saline solution. Two weeks after surgery, all mice had their respiratory movements recorded by video X-ray without any restraint. Behavioral tests were performed to assess the severity of the 6-OHDA lesion. As a result, behavioral tests confirmed mild motor impairments in PD mice as compared to controls. Parameters of respiratory function showed mild alterations in the PD group, suggestive of a restrictive-type respiratory disorder. These results suggest that respiratory alterations in PD may emerge simultaneously to other motor symptoms, and not as a consequence of the latter., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The ability to maintain the body relative to the external environment is important for adaptation to altered gravity. However, the physiological limits for adaptation or the disruption of body orientation are not known. In this study, we analyzed postural changes in mice upon exposure to various low gravities. Male C57BL6/J mice (n = 6) were exposed to various gravity-deceleration conditions by customized parabolic flight-maneuvers targeting the partial-gravity levels of 0.60, 0.30, 0.15 and μ g (<0.001 g). Video recordings of postural responses were analyzed frame-by-frame by high-definition cineradiography and with exact instantaneous values of gravity and jerk. As a result, the coordinated extension of the neck, spine and hindlimbs was observed during the initial phase of gravity deceleration. Joint angles widened to 120%-200% of the reference g level, and the magnitude of the thoracic-curvature stretching was correlated with gravity and jerk, i.e., the gravity deceleration rate. A certain range of jerk facilitated mouse skeletal stretching efficiently, and a jerk of -0.3~-0.4 j (g/s) induced the maximum extension of the thoracic-curvature. The postural response of animals to low gravity may undergo differential regulation by gravity and jerk.