Effects Of Deprivation Research Articles

Serpina3c deficiency aggravates vascular dysfunction and VSMC dysregulation through regulating adamts4 pathway activity in obese mice

Abstract Background Obesity leads to arterial stiffness (AS), which is an independent risk factor for cardiovascular disease. Vascular smooth muscle cell (VSMC) dysfunction is a critical step in the development of AS. Adamts4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) promoting the ECM remodeling can regulate VSMC differentiation. Serpina3c is a serine protease inhibitor that plays a key role in VSMC proliferation and metabolic diseases. Purpose The present study aimed to investigate the function of Serpina3c in high-fat diet (HFD)-induced AS and regulation of VSMC phenotypic switching and possible mechanisms. Methods 8-week-old male Serpina3c-/- and C57BL/6 mice were fed normal diet (ND) or HFD for 12 weeks. The adipocyte-specific Serpina3c overexpression (AAV8-Serpina3c) were constructed and injected in situ into visceral or perivascular adipose tissue (AT) of Serpina3c-/- mice fed a 12-week HFD to test in vivo effect of AT-derived Serpina3c on arterial stiffness. In vivo vascular stiffness was analyzed by obtaining pulse wave velocity (PWV) measurements. Aortic rings were dissected to assess the ex-vivo effects of Serpina3c deprivation on vascular contractile and diastolic function. Elastin van Gieson (EVG) and Hematoxylin-eosin (H&E) staining were implemented to observe the pathological morphology of aortas. IP-Western analysis was performed for identifying Serpina3c-adamts4 interactions. Results The obese WT mice exhibited significantly increased PWV values, compared with ND-fed mice, which were further increased in HFD+Serpina3c-/- mice (Fig. 1A). Phenylephrine-induced vascular constriction was impaired in HFD fed mice and further deteriorated with Serpina3c deficiency (Fig. 1B). No differences were noted in the endothelial-dependent acetylcholine-mediated relaxation in HFD-fed mice. Notably, Serpina3c-/- mice exhibited poorer endothelium-independent sodium nitroprusside induced relaxation (Fig. 1C and D). The HFD+Serpina3c-/- mice showed an increased breakage of elastin fibres and medial thickness compared with the aortas of HFD+WT mice (Fig. 1E and F). Serpina3c deprivation aggravated collagen deposition and matrix metalloproteinases (MMPs, MMP2 and MMP9) accumulation. VSMC contractile gene α smooth muscle actin were upregulated and synthetic phenotype marker osteopontin were downregulated in HFD+WT mice. The effect was more pronounced in aortas with Serpina3c deficiency (Fig. 1G and H). Overexpression of serpina3c in both visceral and perivascular AT or adamts4 deprivation reversed the above phenotypes. Computer simulations and IP-Western results indicate that Serpina3c and adamts4 bind to and maintain the latter low-expression in response to obesity (Fig. 2). Conclusion Serpina3c interacts with adamts4 to maintain contractile phenotype of VSMC and suppress AS development in the context of nutrient excess. Serpina3c is a novel target for the prevention and treatment of obesity associated artery disease.Serpina3c maintains vascular functionSerpina3c interacts with adamts4

Effects of one-night partial sleep deprivation on perivascular space volume fraction: Findings from the Stockholm Sleepy Brain Study.

Sleep issues have been known to be associated with a variety of health risks. Recent research has shown the importance of sleep for brain clearance, with increases in brain clearance occurring during sleep. PVS seen on MRI are known to represent both influx and efflux pathways for the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) in the brain parenchyma, a key process underlying the waste clearance system. 1 Numerous recent studies have found links between sleep disruption and PVS volume changes. However, no study to date has been able to examine within-subject changes in PVS resulting from experimental manipulation of sleep. Our study represents the first within-subject study looking at the effects of partial sleep deprivation on PVS volume fraction using an automated PVS segmentation technique.

How neighbourhood effects vary by achievement level

Abstract After long-standing calls for research into ‘for whom’ neighbourhood matters, the literature has recently gained traction, focussing on background characteristics such as gender, race, and socioeconomic background. However, there is still scarce and only indirect evidence on whether neighbourhood effects vary by children’s academic ability. In this paper, we combine the Neighbourhood Choice Model with quantile regressions to investigate whether neighbourhood effects vary by children’s academic proneness. Using Norwegian register data, we demonstrate heterogeneity in the effects of neighbourhood deprivation as a function of students’ proneness to academic achievement. Students with the very lowest and highest academic potential are the least affected by neighbourhood disadvantage, while those with below average—but not at the lowest end—are most strongly affected. Moreover, while girls are less affected than boys, and children from less educated and affluent families are more affected by neighbourhood disadvantage than their more privileged peers, the effects of these observed moderators are considerably smaller than the heterogeneity observed as a function of academic proneness. Overall, our use of quantile regressions opens up new venues for understanding ‘for whom’ neighbourhoods matter, with individual-level academic vulnerability and strengths being an influential source of neighbourhood effects variation.

Activation of the WNT7B/β-Catenin Pathway Initiates GLUT1 Expression and Promotes Aerobic Glycolysis in Colorectal Cancer Cells

Glucose is an important energy source for tumors, however the molecular mechanisms by which tumor cells regulate glucose uptake remain unclear. In this study, we aimed to investigate the regulation mechanism of the WNT7B/β-catenin pathway for glucose transporter 1 (GLUT1)-mediated glucose metabolism in colorectal cancer. Here, we found that WNT7B expression levels were significantly increased in colorectal cancer tissues and closely associated with the clinical stage and lymph node metastasis in patients with colorectal cancer. Next, we confirmed that WNT7B significantly increased the glucose consumption and lactic acid levels in SW480 cells by overexpressing WNT7B. Additionally, gene and protein levels of GLUT1 were increased in WNT7B-overexpressing SW480 cells. However, WNT7B knockdown reversed these effects. WNT7B also enhanced GLUT1-mediated cell proliferation, invasion, and migration. WNT7B overexpression inhibited the effect of glucose deprivation on apoptosis. The WNT/β-catenin signaling pathway inhibitor, LGK974, inhibited WNT7B secretion, leading to GLUT1 levels downregulation and promotion of cell apoptosis. Ectopic tumor xenograft model experiments revealed that WNT7B promoted tumor progression in mice. Overall, our results suggest that WNT7B promotes β-catenin entry into the nucleus to initiates GLUT1 transcription, increases glucose transport and consumption, and enhances aerobic glycolysis, thus promoting tumor progression in colorectal cancer cells.

UNVEILING THE MECHANISTIC INSIGHTS OF ARGININE DEPRIVATION COMBINED WITH RADIOTHERAPY FOR THE TREATMENT OF GLIOBLASTOMA

Abstract AIMS Glioblastoma is a lethal form of primary brain tumour in adults. Despite surgery, radiation and chemotherapy, life expectancy is short rendering the need for novel therapeutic approaches. Metabolic therapies provide a multifaceted effect in the heterogeneous glioblastoma microenvironment as they target its reprogrammed metabolism while overcoming therapeutic obstacles such as the blood brain barrier. We have shown that arginine deprivation combined with radiation eliminates the tumours in vivo, however, the exact mechanism of action is yet unknown. Here, using spatial transcriptomics we explore the effects of arginine deprivation and radiation, alone and combined, on the glioblastoma microenvironment. METHOD Brains collected from CT2A immunocompetent mice 6 days after treatment with ADI-PEG20 (5 IU) for arginine depletion, radiation (8 Gy) or their combination were analysed by 10X Genomics Spatial Transcriptomics. Bioinformatic analysis was performed using the R package Seurat and the Ingenuity Pathway Analysis (Qiagen). RESULTS The induction of innate immune response was observed with all treatments, however, it was the prevailing element only in the combination treatment. Upregulated pathways in all treatments involved the activation of antigen presentation cells. The pro-inflammatory cascades included key molecules of an immune response such as Type I IFNs, IFN-γ, STAT1, ISG15 and IRFs. Protein translation pathways indicating resistance to treatment dominated the changes caused by the two monotherapies, while they were absent in the combination group. The upregulation of CXCL10 and CCL5 signified the transition to adaptive immune response. Cytosolic DNA sensing by the cGAS-STING was enriched in the radiation and combination groups providing a possible trigger for the innate immune response. Pyroptosis and extracellular matrix remodelling were uniquely presented in the combination group. CONCLUSION Our analysis indicates that arginine deprivation and radiation when combined enhance each other’s effect leading to a fortified immune response that is possibly initiated by cytosolic DNA sensing.

Caffeine Intake Alters Recovery Sleep after Sleep Deprivation.

Caffeine is a well-known psychostimulant reputed to alleviate the deleterious effects of sleep deprivation. Nevertheless, caffeine can alter sleep duration and quality, particularly during recovery sleep. We evaluated the effects of acute caffeine intake on the duration and quality of recovery sleep following total sleep deprivation (TSD), taking into account daily caffeine consumption. Forty-one participants performed a double-blind, crossover TSD protocol (38 h of continuous wakefulness) with acute caffeine or placebo. Caffeine (2.5 mg/kg) or placebo was administered twice during continuous wakefulness (last treatment 6.5 h before bedtime for the recovery night). Polysomnographic measurements were recorded using a connected headband. TSD was associated with a rebound in total sleep time (TST) on the recovery night (+110.2 ± 23.2 min, p < 0.001). Caffeine intake decreased this recovery TST (-30.2 ± 8.2 min p = 0.02) and the N3 sleep stage duration (-35.6 ± 23.2 min, p < 0.01). Caffeine intake altered recovery sleep continuity (increased number of long awakenings), stability (higher stage transition frequency), and organization (less time spent in complete sleep cycle) and decreased the delta power spectral density during NREM sleep. On the recovery night, habitual daily caffeine consumption was negatively correlated with TST in caffeine and placebo conditions and positively correlated with wake after sleep onset (WASO) duration and with the frequency of long (>2 min) awakenings in the caffeine condition only. Acute caffeine intake during TSD affects nighttime recovery sleep, with an interaction with daily consumption. These results may influence advice on caffeine intake for night-shift workers. (NCT03859882).

The Effects of Maternal Deprivation and Adolescent Morphine Exposure on Anxiety-Like Behaviors and Working Memory in Male and Female Rats

The Effects of Maternal Deprivation and Adolescent Morphine Exposure on Anxiety-Like Behaviors and Working Memory in Male and Female Rats

Inequalities in access to and outcomes of cardiac surgery in England: retrospective analysis of Hospital Episode Statistics (2010–2019)

BackgroundWe aimed to characterise the variation in access to and outcomes of cardiac surgery for people in England.MethodsWe included people >18 years of age with hospital admission for ischaemic heart...

Effects of total sleep deprivation on functional connectivity of the anterior cingulate cortex: Insights from resting-state fMRI in healthy adult males

Inadequate sleep significantly impacts an individual's health by compromising inhibitory control and self-regulation abilities. This study employed resting-state functional magnetic resonance imaging (fMRI) to assess the functional connectivity between the anterior cingulate cortex (ACC) and the whole brain in 16 healthy adult males after 36 h of total sleep deprivation. Additionally, this study investigated alterations in individuals' inhibitory control functions and physiological mechanisms following sleep deprivation. The results showed a significant increase in functional connectivity between the ACC, the left angular gyrus, and the right hippocampus following 36 h of continuous sleep deprivation. Conversely, functional connectivity was notably decreased between the ACC and the right insular cortex, right paracingulate gyrus, and bilateral putamen. Furthermore, changes in ACC functional connectivity were significantly correlated with alterations in behavioral performance in the go/no-go task after sleep deprivation. This study contributes to understanding brain network mechanisms in the anterior cingulate gyrus after sleep deprivation. It clarifies the relationship between functional connectivity changes in the anterior cingulate gyrus and inhibitory control post-sleep deprivation.

A comparative study to assess the effect of sleep deprivation on cognitive function among adolescent’s male and female in selected rural and urban areas of district Mohali, Punjab

Adolescence may be a critical period which marks puberty and physical maturation, where there’s a gradual transition between childhood and adulthood. Sleep affects the physical, mental, and emotional development of the adolescents, and it’s a possible impact on their academic performance. Adolescents should sleep 8-10 hours/day on a regular basis to promote optimal health. Poor sleep has multiple effects on adolescent health which includes depression, excessive day time sleepiness and metabolic dysfunctions. Unlike adults, children don’t usually complain of sleep problems or seek treatment.

Morphometric analysis of the intergenerational effects of protein restriction on nephron endowment in mice

BackgroundParental nutritional status is crucial in shaping offspring's kidney development. However, the association between a protein-restrictive diet and its intergenerational impact on kidney development remains unclear. MethodsWe conducted multigenerational morphometric measurements to investigate the effects of parental protein deprivation on offspring kidney development across four generations. F0 mice were divided into two groups and fed a normal protein diet (NPD) or a low-protein diet (LPD) for three weeks before mating and continued these diets throughout gestation and lactation. Body weight (BW), kidney weight (KW), KW/BW ratio, nephron counts, and blood pressure were assessed in F1 pups. To examine paternal effects, we bred CD1 females on an NPD with males on an LPD. BW, KW, KW/BW, and nephron counts were measured at P20. To measure the transgenerational effect of parental LPD on kidney development, F1 offspring (from parents on LPD) were fed NPD upon weaning. These F1 offspring were bred at 6 weeks of age to produce F2, F3 and F4 generations. Kidney metrics were evaluated across generations. ResultsThe average body weight of P0 pups from parents on NPD was 1.61g, while pups from parental LPD weighed an average of 0.869g, a decrease of 54 % (p = 6.9e-11, Wilcoxon test). F1 from parental LPD have significantly smaller kidneys than the control, with an average combined kidney weight of 0.0082g versus 0.0129g, a 37 % decrease (p = 3.2e-02, Wilcoxon test). P20 BW and KW remained low in LPD offspring. These effects persisted for 4 generations (F1 to F4) with an average glomerular count reduction of roughly 20 %. F3 and F4 showed wider variability in glomerular counts but were not statistically significant compared to controls. ConclusionsBoth maternal and paternal LPD significantly affected offspring nephron endowment. Our study underscores the complex nature of nutritional transgenerational effects on kidney development, emphasizing the importance of both maternal and paternal dietary impacts on kidney development and the developmental origin of adult disease.

Glioblastoma Sensitization to Therapeutic Effects by Glutamine Deprivation Depends on Cellular Phenotype and Metabolism.

Glutamine plays an important role in tumor metabolism. It is known that the core region of solid tumors is deprived of glutamine, which affects tumor growth and spread. Here we investigated the effect of glutamine deprivation on cellular metabolism and sensitivity of human glioblastoma cells U87MG and T98G to drugs of various origin: alkylating cytostatic agent temozolomide; cytokine TRAIL DR5-B- agonist of the DR5 receptor; and GMX1778- a targeted inhibitor of the enzyme nicotinamide phosphoribosyltransferase (NAMPT), limiting NAD biosynthesis. Bioinformatics analysis of the cell transcriptomes showed that U87MG cells have a more differentiated phenotype than T98G, and also differ in the expression profile of the genes associated with glutamine metabolism. Upon glutamine deprivation, growth rate of the U87MG and T98G cells decreased. Analysis of cellular metabolism by FLIM microscopy of NADH as well as assessment of lactate content in the medium showed that glutamine deprivation shifted metabolic status of the U87MG cells towards glycolysis. This was accompanied by the increase in expression of the stemness marker CD133, which collectively could indicate de-differentiation of these cells. At the same time, we observed increase in both expression of the DR5 receptor and sensitivity of the U87MG cells to DR5-B. On the contrary, glutamine deprivation of T98G cells induced metabolic shift towards oxidative phosphorylation, decrease in the DR5 expression and resistance toDR5-B. Theeffects of NAMPT inhibition also differed between the two cell lines and were opposite to the effects of DR5-B: upon glutamine deprivation, U87MG cells acquired resistance, while T98G cells were sensitized to GMX1778. Thus, phenotypic and metabolic differences between the two human glioblastoma cell lines caused divergent metabolic changes and contrasting responses to different targeted drugs during glutamine deprivation. These data should be considered when developing treatment strategies for glioblastoma via drug-mediated deprivation of amino acids, as well as when exploring novel therapeutic targets.

The Effect Of Sleep Deprivation On Thermoregulation In Older Adults During Exercise-Heat Stress

The Effect Of Sleep Deprivation On Thermoregulation In Older Adults During Exercise-Heat Stress

Remembering Hypoxia: Uncovering the Long-Term Effects of Transient Oxygen Deprivation on IFN Signaling and Progression of Breast Cancer.

Hypoxia occurs in 90% of solid tumors and is strongly associated with an increased propensity for metastasis. Hypoxia induces tumor progression largely through inducing HIF-mediated transcription, resulting in alterations to tumor cell metabolism, as well as increases in migration and invasion. Hypoxia also results in a myriad of changes to the tumor microenvironment (TME). While many studies have examined the immediate effects of hypoxia on tumor cells and the associated TME, far fewer have focused on the long-term consequences of transient reductions in oxygen. In this issue of Cancer Research, Iriondo and colleagues examined whether short-term exposure to hypoxia leads to a "hypoxic memory" in the context of breast cancer. The authors used established cell lines and circulating tumor cell lines to demonstrate that these cells harbor a hypoxic memory that sustains downregulation of IFN signaling and antigen presentation (AP) pathways that contribute to tumor progression via alterations to tumor cells and the TME. The authors further showed that cells that have experienced hypoxia maintain the reduction in IFN signaling in vivo and are more aggressive. They determined that the hypoxic memory and reduction of IFN signaling can be reversed with a histone deacetylase inhibitor, entinostat, providing a potential means to reverse hypoxia-induced suppression of IFN signaling. As suppression of IFN signaling has the potential to influence both tumor cells and the TME, the identification of a strategy to inhibit long-term suppression of IFN signaling downstream of hypoxia could prove to be an effective means to target tumor progression. See related article by Iriondo et al., p. 3141.

Partial sleep deprivation affects the athletic performance of Sanda athletes: An RCT study

This study explored the effects of partial sleep deprivation (PSD) on Sanda athletes' athletic performance, an area with limited research. Using a randomized crossover controlled trial with 18 male athletes, the PSD group had 4 h of sleep while the NSN group had 8 h. Results showed that after PSD intervention, the RAT time significantly increased compared to the NSN group (P = 0.0311). However, there was no significant change in CMJ (P = 0.2396) or YBT (left leg: P = 0.2767, right leg: P = 0.3225) between the PSD and NSN groups. In the Wingate test, the PSD group exhibited significant reductions in Pmax and Pave at 10s, 30s, and 60s (P＜0.0001), as well as a significant decrease in Prel at 60s (P＜0.0001), with no significant differences in Prel at 10s and 30s. These findings underscore the detrimental impact of limited sleep on anaerobic performance and agility in Sanda athletes, emphasizing the need for proper sleep management for optimal athletic outcomes.

Synaptophysin and GSK-3beta activity in the prefrontal cortex may underlie the effects of REM sleep deprivation and lithium on behavioral functions and memory performance in male rats

Rapid-eye movement (REM) stage of sleep serves a critical role in processing cognitive and behavioral functions. Evidence shows that REM sleep deprivation (REM SD) strongly affects the mood state and cognitive abilities. However, there are many inconsistent reports. Although the exact molecular mechanisms underlying REM SD effects have not well been discovered, however, molecular factors including those affected synaptic plasticity and mood state may be involved. There are two important molecular factors that have not been well studied: synaptophysin and glycogen synthase kinase-3 beta (GSK-3beta). The present study aimed to investigate the role of synaptophysin and GSK-3beta in the modulation of memory and behavioral changes induced by REM SD and lithium (as a potent GSK-3beta inhibitor and mood stabilizer). Multiple platform apparatus was used to induce REM SD for 48 h. Lithium was injected at the dose of 50 mg/kg, intraperitoneal (i.p.). Locomotor activity, anxiety-like behavior, pain threshold, novel object recognition memory, and synaptophysin and GSK-3beta level in the prefrontal cortex were evaluated. Results showed REM SD increased locomotor activity, decreased pain threshold, impaired novel object recognition memory, decreased synaptophysin and increased GSK-3beta levels. Lithium reversed these effects. Anxiety-like behavior was unaffected. For the first time, the present study showed that GSK-3beta and synaptophysin may be involved in the modulation of behavior and cognition induced by REM SD and lithium. In conclusion, we suggested that GSK-3beta upregulation and synaptophysin downregulation may underlie the deleterious effects of REM SD, while lithium may counteract REM SD effects via restoring the level of both.

Recent research on response disequilibrium theory: A concise review.

A resurgence in research on response disequilibrium theory has prompted a concise review of the literature from the past 5 years. Response disequilibrium, also known as response deprivation, attributes reinforcement and punishment effects to constraints on free-operant baseline levels of behavior. By describing clinically relevant behaviors in terms of instrumental and contingent activities, researchers and practitioners can predict intervention outcomes with a disequilibrium model. We summarize the empirical outcomes of disequilibrium-informed interventions across six articles and discuss areas of future research.

Investigating the Effect of Microalgae Bioactive Compounds on Sleep and Mood

Introduction: Nowadays, lack of sleep has led to many serious health problems. Meanwhile, cyanobacteria exhibit bioactive properties such as anti-inflammatory, anti-cancer, anti-bacterial, anti-parasitic, anti-diabetic, anti-viral, antioxidant, rejuvenating and anti-obesity, making them a suitable option for the production of drugs. Sleep and mental health are closely related, and the negative impact of sleep deprivation on overall health and well-being is exacerbated. Methods: In this review article, more than 200 journals on databases such as PubMed, Springer, Wiley، Science Direct, Scopus, Web of Sciences, and the list of open access journals were investigated. Keywords such as "microalgae", "bioactive compounds", "unsaturated fatty acids", "sleep disorders", "mood regulation" and "stress" were used for searching. Results: The results showed that sleep and mental health are closely related, and the negative effect of sleep deprivation on health and overall well-being intensifies is exacerbated. Conventional treatments have a wide range of adverse effects, commonly associated with benzodiazepines and antidepressants. Conclusion: At present, the significant contribution of microalgae bioactive compounds in sleep management and mental health has not been investigated, which is suggested to be widely studied in the near future.

An integrative analysis of cell-specific transcriptomics and nuclear proteomics of sleep-deprived mouse cerebral cortex.

Sleep regulation follows a homeostatic pattern. The mammalian cerebral cortex is the repository of homeostatic sleep drive and neurons and astrocytes of the cortex are principal responders of sleep need. The molecular mechanisms by which these two cell types respond to sleep loss are not yet clearly understood. By combining cell-type specific transcriptomics and nuclear proteomics we investigated how sleep loss affects the cellular composition and molecular profiles of these two cell types in a focused approach. The results indicate that sleep deprivation regulates gene expression and nuclear protein abundance in a cell-type-specific manner. Our integrated multi-omics analysis suggests that this distinction arises because neurons and astrocytes employ different gene regulatory strategies under accumulated sleep pressure. These findings provide a comprehensive view of the effects of sleep deprivation on gene regulation in neurons and astrocytes.

An analysis of Islamic financing access in Nigeria: perspectives of MSME owners

Purpose Funding difficulties are particularly compounded for Muslim entrepreneurs in Nigeria, owing to the dominance of interest-based financial institutions prohibited in Islam. Thus, this study aims to explore the role of awareness of Islamic finance principles in ameliorating financial deprivation and financial anxiety to increase access to Islamic financing among Muslim entrepreneurs. Design/methodology/approach A quantitative survey method of data collection was used to collect data from a total of 208 micro, small and medium enterprises (MSME) owners based on hand-delivered questionnaires. The data was analyzed using a partial least square structural equation model. Findings The result supports the direct negative impact of relative financial deprivation and the positive impact of awareness of Islamic finance principles on access to Islamic finance. However, awareness of Islamic finance principles could not moderate any of the direct relationship. Practical implications This study implies that financial deprivation is detrimental to access to Islamic finance, but financial anxiety has no significant impact. In addition, policymakers and MSME owners could directly foster access to Islamic finance through awareness of Islamic finance principles, though it could not redirect the negative impact of relative financial deprivation on access to Islamic finance. Originality/value The valuable finding here is that the substantial positive impact of awareness of Islamic finance principles on access to Islamic finance is not enough to redirect the negative effect of relative financial deprivation on access to Islamic finance.