Deprivation Stress Research Articles

The Effects of Virtual Learning on the Mental Health and Academic Performance of the Tourism Students of Wesleyan University –Philippines

Students face educational hurdles while adjusting to virtual learning or distance learning. A greater retention percentage is hampered by a variety of factors, including mental health issues. This study was conducted to determine the effects of virtual learning on the mental health and academic performance of 158 Bachelor of Science in Tourism Management students at Wesleyan University – Philippines. One hundred twenty-four, or 78%, of the respondents were female, and the rest were male. The results of the study showed that the mental health of the tourism students during virtual learning was affected by the following: time management, focus/concentration, difficulties with internet connection, and gaining knowledge/developing skills. Those factors have an effect on the respondents’ academic performance in their online classes. The idea of virtual learning while at home affects the mental health of learners, who experience stress, anxiety, depression, panic attacks, self-harming, and sleep deprivation due to the pressures of doing their assignments and submitting them immediately. In this way, the class must also formulate a way to ease those issues in order to regain the self-esteem of learners and uplift their emotional development.

Carotenogenic Activity of Two Hypersaline Greek Dunaliella salina Strains under Nitrogen Deprivation and Salinity Stress

The culture growth and carotenogenic activity of two Greek Dunaliella salina strains (AthU-Al D30 and AthU-Al D31) under stress conditions are investigated herein, with emphasis on β-carotene production as well as on lutein and zeaxanthin. In particular, the strains were cultivated in “standard” conditions (60 ‰ salinity and 1.18 M of NaNO3), under salinity stress conditions (160 ‰ salinity and 1.18 M of NaNO3) and under nitrogen deprivation conditions (60 ‰ salinity and 0 M of NaNO3). In addition to the two Greek strains, the D. salina CCAP 19/18 strain, which has been extensively studied regarding carotenogenesis, is included in this study as a reference. All three strains were found to produce increased amounts of β-carotene when cultivated under nitrogen deprivation conditions, while the AthU-Al D31 strain also produced high amounts of carotenoids under salt stress. The HPLC carotenoid profiles of the strains revealed reduced production of lutein in nitrogen deprivation conditions, coupled with a high production of β-carotene. The strains exhibited various responses in terms of carotenogenic activity, indicating an intraspecific variation in the metabolic reactions related to carotenogenesis.

Analysis of a logical regulatory network reveals how Fe-S cluster biogenesis is controlled in the face of stress.

Iron-sulfur (Fe-S) clusters are important cofactors conserved in all domains of life, yet their synthesis and stability are compromised in stressful conditions such as iron deprivation or oxidative stress. Two conserved machineries, Isc and Suf, assemble and transfer Fe-S clusters to client proteins. The model bacterium Escherichia coli possesses both Isc and Suf, and in this bacterium utilization of these machineries is under the control of a complex regulatory network. To better understand the dynamics behind Fe-S cluster biogenesis in E. coli, we here built a logical model describing its regulatory network. This model comprises three biological processes: 1) Fe-S cluster biogenesis, containing Isc and Suf, the carriers NfuA and ErpA, and the transcription factor IscR, the main regulator of Fe-S clusters homeostasis; 2) iron homeostasis, containing the free intracellular iron regulated by the iron sensing regulator Fur and the non-coding regulatory RNA RyhB involved in iron sparing; 3) oxidative stress, representing intracellular H2O2 accumulation, which activates OxyR, the regulator of catalases and peroxidases that decompose H2O2 and limit the rate of the Fenton reaction. Analysis of this comprehensive model reveals a modular structure that displays five different types of system behaviors depending on environmental conditions, and provides a better understanding on how oxidative stress and iron homeostasis combine and control Fe-S cluster biogenesis. Using the model, we were able to predict that an iscR mutant would present growth defects in iron starvation due to partial inability to build Fe-S clusters, and we validated this prediction experimentally.

SIRT1 promotes glucolipid metabolic conversion to facilitate tumor development in colorectal carcinoma.

Background: Fatty acid oxidation (FAO) is a major alternate energy metabolism pathway in tumor cells subjected to metabolic stress caused by glucose deficiency during rapid progression. However, the mechanism of metabolic reprogramming between glycolysis and FAO in tumor cells is unknown. Therefore, identifying the metabolic glucolipid conversion hub in tumor cells is crucial. Methods: We used single-cell RNA sequencing (scRNA-Seq), RNA sequencing (RNA-Seq), The Cancer Genome Atlas (TCGA), and chromatin immunoprecipitation sequencing (ChIP-Seq) to predict the critical regulator and mechanism of metabolic glucolipid conversion in colorectal cancer (CRC) tumor cells. We used Seahorse metabolic analysis, immunoblotting, immunofluorescence, and immunohistochemical (IHC) technology to verify the prediction and mechanism of this regulator in cancer cell lines, a nude mouse xenograft model, and clinical CRC samples. Results: We demonstrated that sirtuin-1 (SIRT1) was upregulated in CRC cells in response to glucose deprivation and oxidative stress. SIRT1 was also a hub of metabolic glucolipid conversion. SIRT1 upregulation deacetylated β-catenin, translocated it from the nucleus to the cytoplasm, attenuated glycolysis, and was positively correlated with fatty acid oxidation (FAO). Clinical analysis of SIRT1 expression in tumor tissues showed the SIRT1High profile was associated with poor prognosis in CRC patients. SIRT1 interference therapy significantly suppressed tumors in the mouse xenograft model. Conclusions: In hostile, glucose-deficient TMEs, SIRT1 is upregulated, and CRC cells transform the Warburg phenotype to FAO. SIRT1 indicates the frequency of glucolipid transformation and rapid tumor progression and is a promising therapeutic target of CRC.

Cyanidin-3-glucoside Enhances Longevity and Heat Stress Resilience in Drosophila melanogaster

Abstract Background: Anthocyanins have gained significant attention in recent years due to their diverse physiological benefits, which include antioxidant and anti-inflammatory properties. However, research on the impact of pure anthocyanin compounds on lifespan under different stress conditions, remains a relatively unexplored area. This study aimed to investigate the influence of cyanidin-3-glucoside (C3G), a pure anthocyanin compound found in common plants, on the lifespan of Drosophila melanogaster (fruit flies) subjected to stress (i.e. energy deprivation and heat stress) and nonstress conditions. Methods: Flies were exposed to various concentrations of C3G from the time of hatching until natural death for the lifespan assay. For stress assays, a separate cohort of male and female flies was subjected to daily heat stress or food deprivation, and their survival was monitored. Results: We found out that C3G prolonged the lifespan of fruit flies in the presence or absence of heat stress. Interestingly, under energy-deprived conditions, lifespan extension was not evident, and a high dose of C3G even led to a shorter lifespan. Moreover, we observed that the sex of the flies did not significantly influence the lifespan modulation by C3G, regardless of whether they were subjected to stress or nonstress conditions. Conclusion: Overall, these findings suggest that C3G may offer promising benefits in enhancing lifespan under certain conditions, while caution should be exercised in dosage selection, especially in energy-deprived scenarios. Further investigations are required to elucidate the underlying mechanisms responsible for the multifaceted effects of C3G on lifespan, thereby exploring its potential applications in promoting longevity and mitigating stress-related challenges.

A 2-hit model of early life stress and later life restraint stress: Susceptibility or resilience to anxiety and alcohol drinking?

Early life stress adversely influences neurodevelopment and has profound long-term effects on brain function and behavior. Here we measure endogenous stress hormone and determine locomotor, anxiogenic, and operant binge drinking behavior of rats exposed to a 2-hit model of maternal deprivation (MD) stress in infancy followed by acute (ARS) or chronic restraint stress (CRS) paradigms during adolescence/adulthood to determine resiliency or susceptibility to the second stress exposure. Adolescents (n=40) exhibited higher baseline corticosterone (CORT) levels than adults (n=40) and with CRS exposure, showed significantly elevated circulating CORT irrespective of MD exposure status. In adults, MD females had lower baseline CORT levels than controls, whereas MD and control male CORT were indistinguishable. For behavior, N=40 was used in total. In the open field, locomotion was significantly decreased upon ARS, with MD having a significant sustained impact on ambulatory measures with CRS. When tested for anxiety-like behavior on an elevated zero maze, ARS interacted with MD to induce protracted and more profound anxiogenic behavior. Upon CRS, MD anxiogenic behavior was reversed to baseline levels whereas controls, especially males, exceeded baseline levels to spend significantly more time in the open arms of the EZM. Finally, in testing for binge drinking behavior, MD rats lever-pressed significantly more for 10% ethanol on an operant apparatus and exhibited a 3-fold greater drinking baseline than controls. Binge drinking behavior was further elevated with ARS, but quickly returned to the MD baseline even prior to reaching CRS. By contrast, controls had much lower baseline but significantly elevated binge drinking behavior by 3–5-fold in response to ARS which remained elevated through CRS, stabilizing at MD baseline levels. Sex differences were most evident in controls where males exhibited accelerated binge drinking behavior at consistently higher rates than females until Day 21 of CRS where their binge drinking behaviors were similar. There was also a main effect of alcohol binge behavior for MD males, and not females. This study illustrates that, depending on the biobehavioral output, males and females differ in reactivity to stressors where MD stress may confer sex-dependent resilience to subsequent stressors, and males are differently impacted than females.

Assays of Monitoring and Measuring Autophagic Flux for iPSC-Derived Human Neurons and Other Brain Cell Types.

Autophagy is a highly conserved, cytoprotective, catabolic process induced in response to conditions of cellular stress and nutrient deprivation. It is responsible for the degradation of large intracellular substrates such as misfolded or aggregated proteins and organelles. This self-degradative mechanism is crucial for proteostasis in post-mitotic neurons, requiring its careful regulation. Due to its homeostatic role and the implications, it has for certain disease pathologies, autophagy has become a growing area of research. We describe here two assays that can be used as part of a tool kit for measuring autophagy-lysosomal flux in human iPSC-derived neurons.One way to measure autophagic flux is through a western blotting assay, which can be used to analyze two important autophagy proteins: microtubule-associated protein 1 light chain 3 (LC3) and p62. In this chapter, we describe a western blotting assay for use in human iPSC neurons that can be used to quantify these two proteins of interest to measure autophagic flux.In addition to conventional western blotting techniques, more sophisticated tools have come available to readout autophagic flux in a sensitive and high-throughput manner. In the latter portion of this chapter, we describe a flow cytometry assay which utilizes a pH-sensitive fluorescent reporter which can also be used to measure autophagic flux.

The Effects of Financial Stress and Household Socio-Economic Deprivation on the Malnutrition Statuses of Children under Five during the COVID-19 Lockdown in a Marginalized Region of South Punjab, Pakistan.

The lockdown after the COVID-19 pandemic not only caused public health crises and income stress but also put millions at risk of food insecurity and malnutrition across the globe, especially in low and middle-income countries [LMICs]. This study evaluated the effects of financial stress and household socio-economic deprivation on the nutritional status of 1551 children under the age of five during COVID-19 in Pakistan. A self-administered questionnaire was used between November 2020 and April 2021 to collect information on age, height, children's weight, and socio-economic status from 1152 rural households from underdeveloped regions in Punjab, Pakistan. With the help of the proportionate simple random sampling method, this study employed a model (binary logistic regression) to calculate the likelihood of malnourishment. The findings showed that the stunting, underweight, and wasting prevalence rates during COVID-19 were 58.86%, 41.89%, and 8.11%, respectively, in the Bahawalpur region. According to the binary logistic regression analysis, among the household deprivation status (HDS) categories, the risks of childhood malnutrition were lesser in HDS-2 (OR = 0.05, 95% CI: 0. 005-0.879) and HDS-3 (OR = 0.04, 95% CI: 0.008-0.193). Similar to this, within the financial stress index (FSI) categories, the children in homes with medium financial stress had reduced odds of malnutrition (OR = 0.10, 95% CI: 0.018-0.567), and the children in households with low financial stress had reduced risks of malnutrition (OR = 0.006, 95% CI: 0.005-0.061). The proposed research found that stunting and underweight increased by 17.26% and 12.29% during the COVID-19 lockdown in the Bahawalpur region. Additionally, financial stress and socio-economic deprivation strongly affected children's nutritional statuses during the COVID-19 lockdown in the Bahawalpur region of Southern Punjab.

Transcutaneous auricular vagus stimulation (taVNS) improves human working memory performance under sleep deprivation stress

Many human activities require high cognitive performance over long periods, while impairments induced by sleep deprivation influence various aspects of cognitive abilities, including working memory (WM), attention, and processing speed. Based on previous research, vagal nerve stimulation can modulate cognitive abilities, attention, and arousal. Two experiments were conducted to assess the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) to relieve the deleterious effects of sleep deprivation. In the first experiment, 35 participants completed N-back tasks at 8:00 a.m. for two consecutive days in a within-subject study. Then, the participants received either taVNS or earlobe stimulation (active control) intervention in two sessions at random orders after 24 h of sustained wakefulness. Then, they completed the N-back tasks again. In the second experiment, 30 participants completed the psychomotor vigilance task (PVT), and 32 completed the N-back tasks at 8:00 a.m. on the first and second days. Then, they received either taVNS or earlobe stimulation at random orders and finished the N-back and PVT tasks immediately after one hour. In Experiment 1, taVNS could significantly improve the accuracy rate of participants in spatial 3-back tasks compared to active control, which was consistent with experiment 2. However, taVNS did not specifically enhance PVT performance. Therefore, taVNS could be a powerful intervention for acute sleep deprivation as it can improve performance on high cognitive load tasks and is easy to administer.

Collateral Damage: Increasing Risks to Children in a Hostile Immigration Policy Environment.

To identify how recent immigration policies have affected the health of children in immigrant families (CIF). As the number of children and families arriving to the US border has increased, so too have immigration policies directly targeting them. Anti-immigrant policies increase the dangers experienced by children migrating to the USA, while also limiting access to needed resources and medical care for CIF inside the country, including many who are US citizens. The resultant deprivation and toxic stress are associated with adverse consequences for children's physical and mental health.

Levels of Cortisol and Inflammatory Cytokines after The Induction of Various Sleep Deprivation Stress Models in Male Wistar Rats


 
 
 Sleep deprivation (SD) can modulate the production of various cytokines, including pro-inflammatory cytokines such as IL-6, TNF-α, and IFN-γ, and anti-inflammatory cytokines such as IL-10. Paradoxical sleep deprivation (PSD) increases the risk of inflammation but can be relieved by sleep recovery (SR). This study aimed to determine the differences in levels of cortisol and inflammatory cytokines (IL-6, IL-10, TNF-α, dan IFN-γ) in male Wistar rats (Rattus norvegicus) after induction of various sleep deprivation stress models. Twenty-five of male Wistar rats were randomly divided into five groups: control, PSD (20 hours of SD/day for five days), Total Sleep Deprivation or TSD (24 hours of SD/day for five days), PSD+SR (PSD followed by SR), and TSD+SR (TSD followed by SR). The plasma cortisol levels were measured with ELISA, and inflammatory cytokine levels were measured with immunoassay and calculated with fold change. Mean cortisol levels were significantly increased in treatment groups compared to the control group (p=0.029). Multivariate analysis showed no statistically significant difference in inflammatory cytokine levels of IL-6 (p=0.658), IL-10 (p=0.065), TNF-α (p=0.399), and IFN-γ (p=0.283) in all groups. In conclusion, various sleep deprivation stress models affect cortisol levels but not inflammatory cytokine levels of IL-6, IL-10, TNF-α, and IFN-γ among male Wistar rats.
 
 

Predictors of psychological distress and sleep deprivation in caregivers of stroke survivors

BackgroundCaregivers for stroke survivors (CSS) suffer from long hours of care, limited support, and financial difficulties, which often affect their mental health. ObjectivesThis study sought to determine the factors affecting psychological distress and sleep duration among CSS. MethodsWe analyzed cross-sectional data from the 2013 Comprehensive Survey of the Living Conditions for Stroke Survivors and CSS. Linked data from 841 pairs of stroke survivors and CSS were extracted. Kessler's Psychological Distress scale (K6) was used to evaluate psychological distress. CSS who slept less than 5 hours per day were classified as having short sleep duration. Factors predictive of psychological distress and short sleep duration were evaluated using multivariable logistic regression analysis with the forward selection method. ResultsThe mean (SD) age of the CSS was 65.4 (12.5) years. A total of 5.6% of these caregivers presented with serious psychological distress, and 12.0% were sleep deprived. Serious psychological distress was associated with not having someone to consult with, having subjective symptoms within a few days, and having short sleep duration, while having their own houses reduced the risk of serious psychological distress. Furthermore, short sleep duration was associated with stroke survivors in long-term care levels 4 or 5, not having someone to consult with, participation in sponge baths as part of nursing care activities, and having serious psychological distress. ConclusionsThis nationwide survey identified several risk factors for psychological stress and sleep deprivation among CSS and suggests the need for multidimensional approaches to reduce their distress.

Biophysiological stress and sleep deprivation among abdominal transplant surgery fellows: A prospective multi-institutional study using a wearable device

BackgroundTransplant surgery fellowship is physically and emotionally demanding. The objective of this study was to characterize biophysiological stress and sleep patterns among transplant surgery fellows. MethodsParticipating fellows wore a biophysical monitor over a 28-day period and completed biweekly surveys. Sleep patterns were dichotomized as normal or sleep deprived, and heart rate variability (HRV) was used to assess stress. ResultsSeventeen fellows participated. Fellows were frequently sleep deprived (43.9% of nights) and stress was near universal (87.2% of days). Burnout was reported by 2 fellows (11.8%). Only 4 fellows (23.5%) reported compliance with the Transplant Accreditation and Certification Council managed time policy; these fellows experienced fewer days of stress than non-compliant fellows (79.8% vs 89.2% p = 0.02). ConclusionsThis is the first study to quantify sleep deprivation and stress among transplant fellows. Future work is needed to evaluate the effects of sleep deprivation, and stress on burnout and patient outcomes.

A review of the preclinical and clinical studies on the role of the gut microbiome in aging and neurodegenerative diseases and its modulation.

As the world population ages, the burden of age-related health problems grows, creating a greater demand for new novel interventions for healthy aging. Advancing aging is related to a loss of beneficial mutualistic microbes in the gut microbiota caused by extrinsic and intrinsic factors such as diet, sedentary lifestyle, sleep deprivation, circadian rhythms, and oxidative stress, which emerge as essential elements in controlling and prolonging life expectancy of healthy aging. This condition is known as gut dysbiosis, and it affects normal brain function via the brain-gut microbiota (BGM) axis, which is a bidirectional link between the gastrointestinal tract (GIT) and the central nervous system (CNS) that leads to the emergence of brain disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Here, we reviewed the role of the gut microbiome in aging and neurodegenerative diseases, as well as provided a comprehensive review of recent findings from preclinical and clinical studies to present an up-to-date overview of recent advances in developing strategies to modulate the intestinal microbiome by probiotic administration, dietary intervention, fecal microbiota transplantation (FMT), and physical activity to address the aging process and prevent neurodegenerative diseases. The findings of this review will provide researchers in the fields of aging and the gut microbiome design innovative studies that leverage results from preclinical and clinical studies to better understand the nuances of aging, gut microbiome, and neurodegenerative diseases.

Changes in Immune Function during Initial Military Training.

Initial military training (IMT) is a transitionary period wherein immune function may be suppressed and infection risk heightened due to physical and psychological stress, communal living, and sleep deprivation. This study characterized changes in biomarkers of innate and adaptive immune function, and potential modulators of those changes, in military recruits during IMT. Peripheral leukocyte distribution and mitogen-stimulated cytokine profiles were measured in fasted blood samples, Epstein-Barr (EBV), varicella zoster (VZV), and herpes simplex 1 (HSV1) DNA was measured in saliva by quantitative polymerase chain reaction as an indicator of latent herpesvirus reactivation, and diet quality was determined using the healthy eating index measured by food frequency questionnaire in 61 US Army recruits (97% male) at the beginning (PRE) and end (POST) of 22-wk IMT. Lymphocytes and terminally differentiated cluster of differentiation (CD)4+ and CD8+ T cells increased PRE to POST, whereas granulocytes, monocytes, effector memory CD4+ and CD8+ T cells, and central memory CD8+ T cells decreased ( P ≤ 0.02). Cytokine responses to anti-CD3/CD28 stimulation were higher POST compared with PRE, whereas cytokine responses to lipopolysaccharide stimulation were generally blunted ( P < 0.05). Prevalence of EBV reactivation was higher at POST ( P = 0.04), but neither VZV nor HSV1 reactivation was observed. Diet quality improvements were correlated with CD8+ cell maturation and blunted proinflammatory cytokine responses to anti-CD3/CD28 stimulation. Lymphocytosis, maturation of T-cell subsets, and increased T-cell reactivity were evident POST compared with PRE IMT. Although EBV reactivation was more prevalent at POST, no evidence of VZV or HSV1 reactivation, which are more common during severe stress, was observed. Findings suggest increases in the incidence of EBV reactivation were likely appropriately controlled by recruits and immune-competence was not compromised at the end of IMT.

Hypothetical proteins play a role in stage conversion, virulence, and the stress response in the Entamoeba species

Entamoeba histolytica is a protozoan parasite that causes amoebic dysentery and amoebic liver abscess in humans, affecting millions of people worldwide. This pathogen possesses a two-stage life cycle consisting of an environmentally stable cyst and a pathogenic amoeboid trophozoite. As cysts can be ingested from contaminated food and water, this parasite is prevalent in underdeveloped countries and poses a significant health burden. Until recently there was no reliable method for inducing stage conversion in E. histolytica in vitro. As such, the reptilian pathogen, Entamoeba invadens, has long-served as a surrogate. Much remains unclear about stage conversion in these parasites and current treatments for amoebiasis are lacking, as they cause severe side effects. Therefore, new therapeutic strategies are needed.The genomes of these parasites remain enigmatic as approximately 54% of E. histolytica genes and 66% of E. invadens genes are annotated as hypothetical proteins. In this study, we characterized two hypothetical proteins in the Entamoeba species, EIN_059080, in E. invadens, and its homolog, EHI_056700, in the human pathogen, E. histolytica. EHI_056700 has no homolog in the human host. We used an RNAi-based silencing system to reduce expression of these genes in E. invadens and E. histolytica trophozoites. Loss of EIN_059080 resulted in a decreased rate of encystation and an increased rate of erythrophagocytosis, an important virulence function. Additionally, mutant parasites were more susceptible to oxidative stress.Similarly, loss of EHI_056700 in E. histolytica trophozoites resulted in increased susceptibility to oxidative stress and glucose deprivation, but not to nitrosative stress. Unlike the E. invadens mutants, E. histolytica parasites with decreased reduced expression of EHI_056700 exhibited a decreased rate of erythrophagocytosis of and adhesion to host cells. Taken together, these data suggest that these hypothetical proteins play a role in stage conversion, virulence, and the response to stress in the Entamoebae. Since parasites with reduced expression of EHI_056700 show decreased virulence functions and increased susceptibility to physiologically relevant stressors, EHI_056700 may represent a possible therapeutic target for the treatment of amoebiasis.

TSC22D4 interacts with Akt1 to regulate glucose metabolism.

Maladaptive insulin signaling is a key feature in the pathogenesis of severe metabolic disorders, including obesity and diabetes. Enhancing insulin sensitivity represents a major goal in the treatment of patients affected by diabetes. Here, we identify transforming growth factor–β1 stimulated clone 22 D4 (TSC22D4) as a novel interaction partner for protein kinase B/Akt1, a critical mediator of insulin/phosphatidylinositol 3-kinase signaling pathway. While energy deprivation and oxidative stress promote the TSC22D4-Akt1 interaction, refeeding mice or exposing cells to glucose and insulin impairs this interaction, which relies on an intrinsically disordered region (D2 domain) within TSC22D4. Functionally, the interaction with TSC22D4 reduces basal phosphorylation of Akt and its downstream targets during starvation, thereby promoting insulin sensitivity. Genetic, liver-specific reconstitution experiments in mice demonstrate that the interaction between TSC22D4 and Akt1 improves glucose handling and insulin sensitivity. Overall, our findings postulate a model whereby TSC22D4 acts as an environmental sensor and interacts with Akt1 to regulate insulin signaling and glucose metabolism.

Bioengineered Carboxymethylcellulose-Peptide Hybrid Nanozyme Cascade for Targeted Intracellular Biocatalytic-Magnetothermal Therapy of Brain Cancer Cells.

Glioblastoma remains the most lethal form of brain cancer, where hybrid nanomaterials biofunctionalized with polysaccharide peptides offer disruptive strategies relying on passive/active targeting and multimodal therapy for killing cancer cells. Thus, in this research, we report for the first time the rational design and synthesis of novel hybrid colloidal nanostructures composed of gold nanoparticles stabilized by trisodium citrate (AuNP@TSC) as the oxidase-like nanozyme, coupled with cobalt-doped superparamagnetic iron oxide nanoparticles stabilized by carboxymethylcellulose ligands (Co-MION@CMC) as the peroxidase-like nanozyme. They formed inorganic–inorganic dual-nanozyme systems functionalized by a carboxymethylcellulose biopolymer organic shell, which can trigger a biocatalytic cascade reaction in the cancer tumor microenvironment for the combination of magnetothermal–chemodynamic therapy. These nanoassemblies were produced through a green aqueous process under mild conditions and chemically biofunctionalized with integrin-targeting peptide (iRDG), creating bioengineered nanocarriers. The results demonstrated that the oxidase-like nanozyme (AuNP) was produced with a crystalline face-centered cubic nanostructure, spherical morphology (diameter = 16 ± 3 nm), zeta potential (ZP) of −50 ± 5 mV, and hydrodynamic diameter (DH) of 15 ± 1 nm. The peroxide-like nanostructure (POD, Co-MION@CMC) contained an inorganic crystalline core of magnetite and had a uniform spherical shape (2R = 7 ± 1 nm) which, summed to the contribution of the CMC shell, rendered a hydrodynamic diameter of 45 ± 4 nm and a negative surface charge (ZP = −41 ± 5 mV). Upon coupling both nanozymes, water-dispersible colloidal supramolecular vesicle-like organic–inorganic nanostructures were produced (AuNP//Co-MION@CMC, ZP = −45 ± 4 mV and DH = 28 ± 3 nm). They confirmed dual-nanozyme cascade biocatalytic activity targeted by polymer–peptide conjugates (AuNP//Co-MION@CMC_iRGD, ZP = −29 ± 3 mV and DH = 60 ± 4 nm) to kill brain cancer cells (i.e., bioenergy “starvation” by glucose deprivation and oxidative stress through reactive oxygen species generation), which was boosted by the magneto-hyperthermotherapy effect when submitted to the alternating magnetic field (i.e., induced local thermal stress by “nanoheaters”). This groundwork offers a wide avenue of opportunities to develop innovative theranostic nanoplatforms with multiple integrated functionalities for fighting cancer and reducing the harsh side effects of conventional chemotherapy.

Experiences Shape Hippocampal Neuron Morphology and the Local Levels of CRHR1 and OTR.

The dorsal hippocampus is involved in behavioral avoidance regulation. It is unclear how experiences such as the neonatal stress of maternal deprivation (MD) and post-weaning environmental enrichment (EE) affect avoidance behavior and the dorsal hippocampal parameters, including neuronal morphology, corticotrophin-releasing hormone (CRH) signaling, and oxytocin receptor (OTR) level. In male BALB/c mice, we found that MD impaired avoidance behavior in the step-on test compared to non-MD and EE rearing conditions could alleviate that partially. MD increased neuronal branches in the CA1 but decreased synaptic connection levels in the CA2, CA3, and DG. Meanwhile, MD increased the CA1's OTR levels, which negatively correlated with nucleus densities. MD also increased the CA1's and CA2's CRH levels, which positively correlated with CRHR1 levels. However, MD statistically elevated the CA3's CRH receptor 1 (CRHR1) levels, which negatively correlated with nucleus densities and, probably, synaptic connection levels in the CA3. The additive effects of MD and EE maintained similar CRH levels and CRHR1 levels as well as OTR levels in the hippocampal areas as the additive of non-MD and non-EE. However, the presence of MD and EE still decreased the CA1's neuronal branches and the CA2's and DG's synaptic connection levels. The study illustrates how MD and EE affect avoidance behaviors, hippocampal neuron morphology, and CRH and OTR levels. The results indicate that the late-life environmental improvement partially restores the alterations in dorsal hippocampal areas induced by early life stress.

Paeoniflorin Ameliorates Colonic Fibrosis in Rats with Postinfectious Irritable Bowel Syndrome by Inhibiting the Leptin/LepRb Pathway.

Postinfectious irritable bowel syndrome (PI-IBS) is a highly prevalent gastrointestinal disorder associated with immune dysregulation and depression- and anxiety-like behaviors. Through traditional medicine, the active ingredient of Paeoniae Radix called paeoniflorin (PF) was previously found to prevent the symptoms of PI-IBS. However, there is limited information on the effects of PF on intestinal function and depression- and anxiety-like symptoms in PI-IBS animal models. Here, we aimed to determine the effects of PF treatment on the symptoms of PI-IBS in a rat model. The PI-IBS rat model was established via early postnatal sibling deprivation (EPSD), trinitrobenzenesulfonic acid (TNBS), and chronic unpredictable mild stress (CUMS) stimulation and then treated with different dosages of PF (10, 20, and 40 mg/kg) and leptin (1 and 10 mg/kg). The fecal water content and body weight were measured to evaluate the intestinal function, while the two-bottle test for sucrose intake, open field test (OFT), and elevated plus maze test (EMT) were performed to assess behavioral changes. The serum leptin levels were also measured using an enzyme-linked immunosorbent assay. Furthermore, the expressions of leptin and its receptor, LepRb, were detected in colonic mucosal tissues through an immunohistochemical assay. The activation of the PI3K/AKT signaling pathway and the expression of brain-derived neurotrophic factor (BDNF) were also detected via western blotting. After the experimental period, the PI-IBS rats presented decreased body weight and increased fecal water content, which coincided with elevated leptin levels and heightened depression- and anxiety-like behaviors (e.g., low sucrose intake, less frequency in the center areas during OFT, and fewer activities in the open arms during EMT). However, the PF treatment ameliorated these observed symptoms. Furthermore, PF not only inhibited leptin/LepRb expression but also reduced the PI3K/AKT phosphorylation and BDNF expression in PI-IBS rats. Notably, cotreatment with leptin (10 mg/kg) reduced the effects of PF (20 mg/kg) on colonic fibrosis, leptin/LepRb expression, and PI3K/AKT activation. Therefore, our findings suggest that leptin is targeted by PF via the leptin/LepRb pathway, consequently ameliorating the symptoms of PI-IBS. Our study also contributes novel insights for elucidating the pharmacological action of PF on gastrointestinal disorders and may be used for the clinical treatment of PI-IBS in the future.