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At least 415 records · Page 23

Integrin alpha 6 as a stemness driver is a novel promising target for HPV (+) head and neck squamous cell carcinoma

Although the incidence rates of head and neck squamous cell carcinoma (HNSCC) associated with human papilloma virus (HPV) infection have recently been on the rise, the underlying mechanism of its tumorigenesis remains largely unknown. Here, we investigated whether HNSCC cells with high expression of integrin alpha 6 (ITGα6), one of the HPV receptors, have a preference during HPV infection. In addition, we examined the gain or loss of function of the ITGα6 gene in HPV + ve HNSCC cells, as well as its prognostic value in patients with HNSCC. HPV pseudovirus was found to be more infective, with HNSCC cells featuring an overexpressed ITGα6 gene compared to the control cells. Overexpression and suppression of ITGα6 respectively increases and decreases stemness phenotypes of HPV + ve HNSCC cells. Furthermore, ITGα6 can regulate stemness by partially mediating AKT pathway in HPV + ve HNSCC cells. Finally, patients with HPV + ve HNSCC had a poor prognosis in cases of elevated ITGα6 expression; however, the expression levels of ITGα6 did not influence the survival rates of HPV-negative HNSCC patients. In conclusion, ITGα6 can serve as a potential therapeutic target for HPV + ve HNSCC cancer-like stem cells (CSCs).

60 APPLIED LIFE SCIENCES↗

Detection of Head and Neck Cancer Based on Longitudinal Changes in Serum Protein Abundance

Head and Neck Squamous Cell Carcinoma (HNSCC) is significantly represented in the military population with substantial impact on military operations. Two-thirds of new HNSCC cases are first diagnosed at advanced stage III or IV with lymph node metastases. Thus, there is an urgent need of biomarkers for early detection and risk stratification. Archived serum samples from the Department of Defense Serum Repository provide a unique resource for longitudinal studies of HNSCC in the military and the identification of early detection biomarkers. Methods: We identified 175 patients diagnosed with HNSCC with 175 matched healthy controls and retrieved a total of 978 serum samples drawn at the time of diagnosis, 2 and 4 years prior to diagnosis, and 2 years after diagnosis. Following immunoaffinity depletion, serum samples were analyzed by targeted proteomics assays for multiplexed quantification of a panel of 146 candidate protein biomarkers from the curated literature. Results: We derived a 13-protein signature that distinguishes case versus controls based on longitudinal changes in serum protein concentration. The abundances of each of the 13 proteins remain constant over time in control subjects. The area under the curve for the derived random forest classifier was 0.90. Conclusions: This 13-protein classifier is highly promising for detection of HNSCC prior to overt symptoms. Impact: Use of longitudinal samples has significant potential to identify biomarkers for detection and risk stratification.

59 BASIC BIOLOGICAL SCIENCES↗

Image-based time series analysis to establish differential disease progression for two Fusarium head blight pathogens in oat spikelets with variable resistance

Oat-based value-added products have increased their value as healthy foodstuff. Fusarium head blight (FHB) infections and the mycotoxins accumulated to the oat seeds, however, pose a challenge to oat production. The FHB infections are predicted to become more prevalent in the future changing climates and under more limited use of fungicides. Both these factors increase the pressure for breeding new resistant cultivars. Until now, however, genetic links in oats against FHB infection have been difficult to identify. Therefore, there is a great need for more effective breeding efforts, including improved phenotyping methods allowing time series analysis and the identification of molecular markers during disease progression. To these ends, dissected spikelets of several oat genotypes with different resistance profiles were studied by image-based methods during disease progression by Fusarium culmorum or F. langsethiae species. The chlorophyll fluorescence of each pixel in the spikelets was recorded after inoculation by the two Fusarium spp., and the progression of the infections was analyzed by calculating the mean maximum quantum yield of PSII (F v /F m ) values for each spikelet. The recorded values were (i) the change in the photosynthetically active area of the spikelet as percentage of its initial size, and (ii) the mean of F v /F m values of all fluorescent pixels per spikelet post inoculation, both indicative of the progression of the FHB disease. The disease progression was successfully monitored, and different stages of the infection could be defined along the time series. The data also confirmed the differential rate of disease progression by the two FHB causal agents. In addition, oat varieties with variable responses to the infections were indicated.

oats↗

Ghrelin Modulates Differential Expression of Genes Relevant to Immune Activities and Antimicrobial Peptides in Primary Head Kidney Cells of Rainbow Trout ( Oncorhynchus mykiss )

Ghrelin is a peptide hormone/cytokine that regulates metabolic processes and plays essential roles in the immune system. To evaluate the immunomodulatory actions of ghrelin isoforms in rainbow trout (RT), an in vitro model was utilized with primary cells isolated from fish head kidney (HKD). These RT-HKD cells were treated with synthetic rainbow trout ghrelin and its truncated isoform, desVRQ-ghrelin, over time (0, 2, 4, and 24 h). Reverse transcriptase-coupled qPCR was used to measure the differential expression patterns of genes relevant to various immune processes and genes of antimicrobial peptides. Ghrelin isoform treatments resulted in functional perturbations that displayed overlapping and divergent patterns of gene expression. The differing actions between the two ghrelin isoforms on various assessed genes, and at differing time points, suggested that the two analogs may activate unique pathways, thereby eliciting distinct responses in fish immunity.

59 BASIC BIOLOGICAL SCIENCES↗

The Use of Artificial Intelligence in Head and Neck Cancers: A Multidisciplinary Survey

Artificial intelligence (AI) approaches have been introduced in various disciplines but remain rather unused in head and neck (H&N) cancers. This survey aimed to infer the current applications of and attitudes toward AI in the multidisciplinary care of H&N cancers. From November 2020 to June 2022, a web-based questionnaire examining the relationship between AI usage and professionals’ demographics and attitudes was delivered to different professionals involved in H&N cancers through social media and mailing lists. A total of 139 professionals completed the questionnaire. Only 49.7% of the respondents reported having experience with AI. The most frequent AI users were radiologists (66.2%). Significant predictors of AI use were primary specialty (V = 0.455; p < 0.001), academic qualification and age. AI’s potential was seen in the improvement of diagnostic accuracy (72%), surgical planning (64.7%), treatment selection (57.6%), risk assessment (50.4%) and the prediction of complications (45.3%). Among participants, 42.7% had significant concerns over AI use, with the most frequent being the ‘loss of control’ (27.6%) and ‘diagnostic errors’ (57.0%). This survey reveals limited engagement with AI in multidisciplinary H&N cancer care, highlighting the need for broader implementation and further studies to explore its acceptance and benefits.

60 APPLIED LIFE SCIENCES↗

Effects of 17 days of head-down bed rest on hydro-electrolytic regulation in men

Prolonged periods of head-down bed rest (HDBR) are commonly used to mimic the effects of microgravity. HDBR has been shown to produce, as in space, a cephalad redistribution of circulating blood volume with an increase in central blood volume which induces the early adaptations in blood volume regulating hormones. Changes in atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity and aldosterone have been observed. Many reports describe these endocrine adaptations but few investigations of rhythms are in the literature. We proposed to evaluate the circadian rhythms of the hormones and electrolytes involved in the hydro-electrolytic regulation during a HDBR study which was designed to simulate a 17-day spaceflight (Life and Microgravity Spacelab experiment, LMS, NASA).

NASA Center ARC↗

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

Clinical Trial↗

Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans

This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness. Additionally, an exercise countermeasure group was included to identify whether exercise during bed rest might counteract any vasoconstrictor deficits that arose during HDBR. Twenty-two subjects underwent 14 days of strict 6 degrees HDBR. Eight of these 22 subjects did not exercise during HDBR, while 14 of these subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed rest heart rate maximum. To assess alpha-adrenergic vasoconstrictor responsiveness, intradermal microdialysis was used to locally administer norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler flowmetry) was monitored over microdialysis membranes. Nonlinear regression modeling was used to identify the effective drug concentration that caused 50% of the cutaneous vasoconstrictor response (EC(50)) and minimum values from the SkBF-NE dose-response curves. In addition, the effects of HDBR on nonadrenergic cutaneous vasoconstriction were assessed via the venoarteriolar response of the forearm and leg. HDBR did not alter EC(50) or the magnitude of cutaneous vasoconstriction to exogenous NE administration regardless of whether the subjects exercised during HDBR. Moreover, HDBR did not alter the forearm venoarteriolar response in either the control or exercise groups during HDBR. However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction due to the venoarteriolar response in the leg, and this response was similarly reduced in the exercise group. These data suggest that HDBR does not alter cutaneous vasoconstrictor responses to exogenous NE administration, whereas cutaneous vasoconstriction of the leg due to the venoarteriolar response is reduced after HDBR. It remains unclear whether attenuated venoarteriolar responses in the lower limbs contribute to reduced orthostatic tolerance after bed rest and spaceflight.

NASA Discipline Cardiopulmonary↗

Hormonal changes during 17 days of head-down bed-rest

We investigated in six men the impact of 17 days of head-down bed rest (HDBR) on the daily rhythms of the hormones involved in hydroelectrolytic regulation. This HDBR study was designed to mimic a real space flight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of Growth Hormone (GH), Cortisol, 6 Sulfatoxymelatonin, Normetadrenaline (NMN) and Metadrenaline (NM) was determined. A decrease in urinary cortisol excretion during the night of HDBR was noted. For GH, a rhythm was found before and during HDBR. The rhythm of melatonin, evaluated with the urine excretion of 6 Sulfatoxymelatonin (aMT6S), the main hepatic metabolite, persisted throughout the experiment without any modification to the level of phase. A decrease during the night was noted for normetadrenaline urinary derivates, but only during the HDBR.

Non-NASA Center↗

Is the spatial distribution of brain lesions associated with closed-head injury in children predictive of subsequent development of posttraumatic stress disorder?

PURPOSE: To determine whether there is an association between the spatial distributions of lesions detected at magnetic resonance (MR) imaging of the brain in children, adolescents, and young adults after closed-head injury (CHI) and development of the reexperiencing symptoms of posttraumatic stress disorder (PTSD). MATERIALS AND METHODS: Data obtained in 94 subjects without a history of PTSD as determined by parental interview were analyzed. MR images were obtained 3 months after CHI. Lesions were manually delineated and registered to the Talairach coordinate system. Mann-Whitney analysis of lesion distribution and PTSD status at 1 year (again, as determined by parental interview) was performed, consisting of an analysis of lesion distribution versus the major symptoms of PTSD: reexperiencing, hyperarousal, and avoidance. RESULTS: Of the 94 subjects, 41 met the PTSD reexperiencing criterion and nine met all three PTSD criteria. Subjects who met the reexperiencing criterion had fewer lesions in limbic system structures (eg, the cingulum) on the right than did subjects who did not meet this criterion (Mann-Whitney, P =.003). CONCLUSION: Lesions induced by CHI in the limbic system on the right may inhibit subsequent manifestation of PTSD reexperiencing symptoms in children, adolescents, and young adults. Copyright RSNA, 2002.

Non-NASA Center↗

Effect of 6 degrees head-down tilt on cardiopulmonary function: comparison with microgravity

BACKGROUND: Head-down tilt (HDT) of 6 degrees is a commonly used model of weightlessness, but there are few comparisons with actual microgravity. HYPOTHESIS: Our study was designed to prove that the changes in cardiopulmonary function seen in HDT would be similar to those seen in microgravity. METHODS: We compared measurements of cardiovascular and pulmonary function from three separate spaceflights of 14 to 17 d duration, with data collected during a 17-d period of HDT. RESULTS: HDT proved a good model of the cardiovascular response to microgravity, resulting in increases in cardiac output and stroke volume of a similar magnitude to those seen in microgravity, with a concomitant reduction in heart rate. By contrast, HDT was a poor model of the effects of microgravity on pulmonary ventilation and gas exchange. CONCLUSION: Pulmonary function in HDT approximated the changes seen in the 1-G supine posture, while in microgravity this was much closer to that seen in the 1-G upright position. The differences probably reflect the fact that changes in cardiovascular function result primarily from fluid shifts within the entire body, whereas changes in pulmonary ventilation are primarily a result of mechanical influences on the lung and chest and abdominal wall.

NASA Discipline Cardiopulmonary↗