High oxidative stress, Th1/Th17 immune response, M1 macrophage inflammation, and cell death are associated with cardiovascular diseases. Controlled oxidative stress, Th2/Treg anti-tumor immune response, M2 macrophage inflammation, and survival are associated with cancer. MiR-21 protects against cardiovascular diseases but may induce tumor growth by retaining the anti-inflammatory M2 macrophage and Treg phenotypes and inhibiting apoptosis. Down-regulation of let-7, miR-1, miR-9, miR-16, miR-20a, miR-22a, miR-23a, miR-24a, miR-26a, miR-29, miR-30a, miR-34a, miR-124, miR-128, miR-130a, miR-133, miR-140, miR-143-145, miR-150, miR-153, miR-181a, miR-378, and miR-383 may aid cancer cells to escape from stresses. Upregulation of miR-146 and miR-223 may reduce anti-tumor immune response together with miR-21 that also protects against apoptosis. MiR-155 and silencing of let-7e, miR-125, and miR-126 increase anti-tumor immune response. MiR expression depends on oxidative stress, cytokines, MYC, and TGF-β, and expression of silencing lncRNAs and circ-RNAs. However, one lncRNA or circ-RNA may have opposite effects by targeting several miRs. For example, PVT1 induces apoptosis by targeting miR-16a and miR-30a but inhibits apoptosis by silencing miR-17. In addition, levels of a non-coding RNA in a cell type depend not only on expression in that cell type but also on an exchange of microvesicles between cell types and tumors. Although we got more insight into the function of a growing number of individual non-coding RNAs, overall, we do not know enough how several of them interact in functional networks and how their expression changes at different stages of disease progression.

Preeclampsia (PE) is a serious medically important disorder of human pregnancy, which features de novo pregnancy-induced hypertension and proteinuria. The severe form of PE can progress to eclampsia, a convulsive, life-threatening condition. When placental growth and perfusion are abnormal, the placenta experiences oxidative stress and subsequently secretes abnormal amounts of certain pro-angiogenic factors (eg, PlGF) as well as anti-angiogenic factors (eg, sFlt-1) that enter the maternal circulation. The net effect is damage to the maternal vascular endothelium, which subsequently manifests as the clinical features of PE. Other than delivery of the fetus and placenta, curative treatments for PE have not yet been forthcoming, which reflects the complexity of the clinical syndrome. A major source of reactive oxygen species that contributes to the widespread maternal vascular endothelium damage is the PE-affected decidua. The role of decidua-derived mesenchymal stem/stromal cells (MSC) in normotensive and pathological placenta development is poorly understood. The ability to respond to an environment of oxidative damage is a "universal property" of MSC but the biological mechanisms that MSC employ in response to oxidative stress are compromised in PE. In this review, we discuss how MSC respond to oxidative stress in normotensive and pathological conditions. We also consider the possibility of manipulating the oxidative stress response of abnormal MSC as a therapeutic strategy to treat preeclampsia.

The relationship between chronic stress and chronic disease (including mental illness) is well established: HPA-axis hyperactivity leads to hormonal dysregulation of primary mediators (eg, glucocorticoids, cytokines, etc.), allostatic overload, and neurological degradation, followed by clinical manifestations of disease. Amid the largest public health crisis of the century lay a myriad of challenges pushing people beyond their limit. From experiencing loss of connection or dealing with loss of life to financial shocks of COVID-19 lockdowns or infection by the SARS-CoV-2 virus, stress is at an all-time high, threatening both brain and mental health at scale. Fortunately, there is a way forward: the neuroscience of resilience teaches us that it is possible to resist, recover, and redirect the brain from trauma to re-establish balance in the body and improve well-being. At the same time, health follows a social gradient: adverse and protective psychosocial factors are shaped by wider social and economic determinants of health. This paper argues the neurobiology of stress is not separate from health disparities linked to adverse factors (ie, stress) created by complex social and economic contexts. Therefore, the field of neuroscience is challenged to inform multi-context and multi-level approaches and engage with decision-makers to enact policies and interventions aimed at promoting the resilient element in a wider population health context. Undoubtedly, achieving such a goal for current and future generations to benefit and lead healthier lives requires a heroic effort from all key stakeholders. The cost of willful neglect to resolve these issues is too expensive.

Chronic back pain (CBP) is a common symptom throughout the world, and those undergoing it often experience a profound degradation of life. Despite extensive research, it remains an elusive symptom. In most cases, CBP is "non-specific," since bio-mechanisms examined in the clinic do not account for it; another way of saying this is that it is "of obscure origins." This paper re-directs attention towards origins that are distal and usually out of sight from the vantage point of the clinic. CBP as considered here is non-specific, persists ≥ 3 months, and, additionally, interferes with activities of daily life, such as family interaction or work. A theory proposed in the paper draws upon Durkheim's Suicide to explain why exposures in the distal social contexts of family and workplace are fundamentally implicated in CBP. The theory is formed out of previously published studies on family and workplace social contexts of CBP and, in effect, provides a theoretical framework with which to review them. After treatment of CBP in the clinic, patients return to family and workplace contexts. Unless exposures in these contexts are addressed, they serve as continually renewing sources of CBP that remain unabated regardless of mechanism-based treatment in the clinic.

Psychological trauma is unique in that it is an environmental event that could induce biological changes and post-traumatic stress disorder (PTSD), depression, or other mood disorders in some patients. On the other hand, there may be no psychopathology (in most cases), or even sometimes post-traumatic growth and resilience. According to the DSM-5, trauma is a prerequisite for PTSD and traumatic stress disorder, but not for depressive episodes or mood disorders, or other psychiatric conditions. This paper brings attention to the preliminary literature on transgenerational inheritance due to trauma exposure and its societal and cultural implications. There is accumulating evidence that exposure to trauma can be passed transgenerationally through epigenetic inheritance leading to changes in gene expression and possible disorders or resilience. The effects of resilience from transgenerational inheritance have not been studied, but should be, for a full understanding not only of the disease risk across generations, but also of its social and cultural implications. The epigenetic pathologic effects across generations also need further studies, as the current research is preliminary; larger replications are needed for definitive and more complete understanding. I present here a glimpse of where we are, a vision of where we should go in terms of future research direction for disease risk transmission, and recommend studies of resilience and post-traumatic growth across generations, as well as other studies related to the societal implications at the population level.

Elevated social fear in infancy poses risk for later social maladjustment and psychopathology. Hair cortisol concentration (HCC), an index of cumulative cortisol exposure, and diurnal salivary cortisol slope, a biomarker of acute stress regulation, have been associated with social fear behaviors in childhood; however, no research has addressed their relations in infancy. Elucidating potential biomarkers of infant social fear behaviors, as well as environmental factors associated with these biomarkers, may grant insights into the ontogeny of fear behaviors that increase risk for internalizing and externalizing psychopathologies later in life. The current study used multiple linear regression to examine if infant HCC, infant diurnal cortisol slope, and income-to-needs ratios (ITN) were differentially associated with observed social fear responses to a Stranger Approach task at 12 months. Using a sample of 90 infants (Mage = 12.26m, SD = 0.81m, 50% female), results indicated that increased infant HCC was associated with increased distress vocalizations during the Stranger Approach task, while steeper diurnal cortisol slope was associated with fewer distress vocalizations. Ordinary least squares path analyses did not reveal group differences between economically strained and non-strained infants in how cortisol measures and social fear responses related. Findings underscore very early psychobiological correlates of fearfulness that may increase risk for fear-related disorders and adverse mental health symptomology across childhood.

Maternal prenatal distress is associated with child outcomes, including health, neurocognitive, and socio-emotional development. Knowledge on underlying mechanisms is limited, yet relevant for prevention and intervention. This study investigated whether maternal prenatal distress predicts specific caregiving practices that are known for their effects on child outcomes. Caregiving practices studied were maternal caregiving quality and the initiation and course of breastfeeding and room-sharing. We hypothesized that more maternal prenatal distress would be associated with altered caregiving practices. Participants were 174 healthy mother-child dyads. During the 37th week of pregnancy maternal self-reported distress was assessed using questionnaires, and physiological stress by collecting saliva cortisol. Maternal caregiving quality was observed in postnatal week 5 during infant bathing. Weekly diaries on breastfeeding and daily diaries on room-sharing were completed during the first 6 postnatal months. In a regression analysis, no associations between maternal prenatal distress and caregiving quality were found. Multilevel analyses indicated that maternal prenatal evening cortisol was positively related to the initiation of breastfeeding and room-sharing. Replications are warranted, but these results suggest that breastfeeding and room-sharing initiation may be part of a mechanism underlying links between maternal prenatal physiological stress and child outcomes. As other prenatal cortisol markers and self-reported distress were not found to be related to the caregiving practices, it is likely that alternative mechanisms (co-)exist in explaining links between maternal prenatal distress and child outcomes. Future replication research including child outcomes and (other) potential mechanisms will inform prevention and intervention programs fostering healthy pregnancies and child development.

Prenatal stress is a neuropsychiatric risk factor, and effects may be mediated by prenatal oxidative stress. Cell types in the brain sensitive to oxidative stress-cortical microglia and cortical and hippocampal interneurons-may be altered by oxidative stress generated during prenatal stress and may be neurobiological substrates for altered behavior. Our objective was to determine the critical nature of oxidative stress in prenatal stress effects by manipulating prenatal antioxidants. CD1 mouse dams underwent restraint embryonic day 12 to 18 three times daily or no stress and received intraperitoneal injections before each stress period of vehicle, N-acetylcysteine (200 mg/kg daily), or astaxanthin (30 mg/kg before first daily stress, 10 mg/kg before second/third stresses). Adult male and female offspring behavior, microglia, and interneurons were assessed. Results supported the hypothesis that prenatal stress-induced oxidative stress affects microglia; microglia ramification increased after prenatal stress, and both antioxidants prevented these effects. In addition, N-acetylcysteine or astaxanthin was effective in preventing distinct male and female interneuron changes; decreased female medial frontal cortical parvalbumin interneurons was prevented by either antioxidant; increased male medial frontal cortical parvalbumin interneurons was prevented by N-acetylcysteine and decreased male hippocampal GAD67GFP+ cells prevented by astaxanthin. Prenatal stress-induced increased anxiety-like behavior and decreased sociability were not prevented by prenatal antioxidants. Sensorimotor gating deficits in males was partially prevented by prenatal astaxanthin. This study demonstrates the importance of oxidative stress for persistent impacts on offspring cortical microglia and interneurons, but did not link these changes with anxiety-like, social, and sensorimotor gating behaviors.

Law enforcement personnel are required to respond to a variety of dangerous, potentially life-threatening high stress scenarios. Virtual reality (VR)-based training has been shown to attenuate stress responses; however, little is known about the acute stress response from VR exposure. This study examined the impact of participating in a VR-based active shooter training drill (ASD) on markers of physiological stress as well as potential differences in men and women. To examine the impact of participation in a ~50 sec VR-based ASD, 29 subjects (n = 29; 17 males, 12 females) participated in a quasi-experimental single group design. Saliva samples were collected and analyzed from 27 of the 29 subjects a total of four times 1) 30-min prior to, 2) 5-min prior to, 3) 5-min after, and 4) 30-min after the ASD and analyzed for α-amylase (AA) activity and concentrations of secretory immunoglobulin-A (SIgA), cortisol (CORT), and uric acid (UA). Participation in the ASD resulted in a significant (p < 0.05) increase in salivary stress markers AA and SIgA. In addition, lower concentrations of CORT and UA were found in women compared to men. These findings have implications for law enforcement and/or military personnel that may seek to implement a VR-based training into their training regimen. Future studies should investigate the impact of longitudinal participation in ASD interventions to determine if this is an effective training method to reduce stress responses to real life active shooter training drills.

Successful hematopoietic cell transplantation (HCT) depends on rapid engraftment of the progenitor and stem cells that will reestablish hematopoiesis. Rap1A and Rap1B are two closely related small GTPases that may affect platelet and neutrophil engraftment during HCT through their roles in cell adhesion and migration. β-adrenergic signaling may regulate the participation of Rap1A and Rap1B in engraftment through their inhibition or activation. We conducted a correlative study of a randomized controlled trial evaluating the effects of the nonselective β-antagonist propranolol on expression and prenylation of Rap1A and Rap1B during neutrophil and platelet engraftment in 25 individuals receiving an autologous HCT for multiple myeloma. Propranolol was administered for 1 week prior to and 4 weeks following HCT. Blood was collected 7 days (baseline) and 2 days (Day -2) before HCT, and 28 days after HCT (Day +28). Circulating polymorphonuclear cells (PMNC) were isolated and analyzed via immunoblotting to determine levels of prenylated and total Rap1A versus Rap1B. Twelve participants were randomized to the intervention and 13 to the control. Rap1A expression significantly correlated with Rap1B expression. Rap1B expression significantly correlated with slower platelet engraftment; however, this association was not observed in the propranolol-treated group. There were no significant associations between neutrophil engraftment and Rap1A or Rap1B expression. Post hoc exploratory analyses did not reveal an association between social health variables and Rap1A or Rap1B expression. This study identifies a greater regulatory role for Rap1B than Rap1A in platelet engraftment and suggests a possible role for β-adrenergic signaling in modulating Rap1B function during HCT.

Background: The psychological problems of Shidu Parents (SDP) under the China's One-Child Policy have been documented. The purpose of this study was to investigate the relationships among personality types, social support, and post-traumatic stress disorder (PTSD) in SDP. Methods: The PTSD Checklist-Civilian Version (PCL-C), The Big Five Personality Traits (NEO), and Social Support Revalued Scale (SSRS) were administered to the sample of 149 SDP who were over 50 years old and had lost their only child more than one year ago. Results: Among SDP, mothers were more likely to develop PTSD than fathers (χ2 = 11.16, p < 0.01). Parents who were extraverted had a lower risk of developing PTSD-related symptoms (χ2 = 8.58, p < 0.01), and the effect of neuroticism was significant (χ2 = 23.73, p < 0.01). The more social support parents utilized, the lower the incidence of PTSD (t = 4.56, p < 0.01). The result of multilevel linear regression showed that sex, neuroticism, and objective social support remained significantly different after combining all personality types and social support systems in the same model. Social support partially mediated the relationship between neuroticism and PTSD. Meanwhile, it was a complete mediator between extraversion and PTSD. Conclusions: Female sex/gender, neuroticism, and introversion were risk factors of developing PTSD, while receiving social support protected SDP from developing PTSD symptoms. Losing an only child is undoubtedly an enormous disaster for the family, which has become a huge, unavoidable social problem that must be addressed in China.

Background: Renovascular hypertension elicits cardiac damage and remodeling. Two-kidney, one-clip (2K1C) is an experimental model used to study hypertension pathophysiology. In this model, the renin-angiotensin-system (RAS) is overactive due to renal artery stenosis, leading to cardiac remodeling. Redox mechanisms underlying RAS activation mediate hypertension-induced cardiovascular damage. Preclinical studies and clinical trials demonstrated resveratrol's protective effects in cardiovascular diseases, mainly attributed to its antioxidant properties. We hypothesized resveratrol alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor would be beneficial against cardiac damage caused by renovascular hypertension. Objective: We investigated the benefits of resveratrol against cardiac remodeling in 2K1C rats compared with captopril. Methods: Male Wistar rats underwent unilateral renal stenosis - 2K1C Goldblatt model of hypertension. Systolic Blood Pressure (SBP) was measured before and 6 weeks after surgery. Hypertensive 2K1C rats presented SBP≥160 mmHg. From the 6th week after the surgery, the animals received oral resveratrol (20 mg/kg), captopril (12 mg/kg), or their combination for 3 times per week for 3 weeks. Whole heart hypertrophy was evaluated. Histological assays assessed left ventricle hypertrophy and fibrosis. Results: Renovascular hypertension caused cardiac hypertrophy, accompanied by increased myocyte diameter and collagen deposition. Resveratrol reduced 2K1C rats' SBP and whole heart hypertrophy, independently of captopril. Resveratrol caused a higher reduction in ventricular hypertrophy than captopril. Collagen deposition was greater reduced by 2K1C treated only with resveratrol than with captopril alone or combined with resveratrol. Conclusion: Independent of captopril, resveratrol prompts cardioprotective effects on cardiomyocyte remodeling and fibrosis resulting from renovascular hypertension in 2K1C rats.

One aspect of the Reactive Scope Model is wear-and-tear, which describes a decrease in an animal's ability to cope with a stressor, typically because of a period of chronic or repeated stressors. We investigated whether wear-and-tear due to chronic stress would accelerate a transition from phase II to phase III of fasting. We exposed house sparrows (Passer domesticus) to three weeks of daily fasts combined with daily intermittent repeated acute stressors to create chronic stress, followed by two weeks of daily fasts without stressors. We measured circulating glucose, β-hydroxybutyrate (a ketone), and uric acid in both fasted and fed states. We expected birds to be in phase II (high fat breakdown) in a fasted state, but if wear-and-tear accumulated sufficiently, we hypothesized a shift to phase III (high protein breakdown). Throughout the experiment, the birds exhibited elevated β-hydroxybutyrate when fasting but no changes in circulating uric acid, indicating that a transition to phase III did not occur. In both a fasted and fed state, the birds increased glucose mobilization throughout the experiment, suggesting wear-and-tear occurred, but was not sufficient to induce a shift to phase III. Additionally, the birds exhibited a significant decrease in weight, no change in corticosterone, and a transient decrease in neophobia with chronic stress. In conclusion, the birds appear to have experienced wear-and-tear, but our protocol did not accelerate the transition from phase II to phase III of fasting.