Mesenchymal-epithelial transition regulates initiation of pluripotency exit before gastrulation.

The pluripotent epiblast gives rise to all tissues and organs in the adult body. Its differentiation starts at gastrulation, when the epiblast generates mesoderm and endoderm germ layers through epithelial-mesenchymal transition (EMT). Although gastrulation EMT coincides with loss of epiblast pluripotency, pluripotent cells in development and in vitro can adopt either mesenchymal or epithelial morphology. The relationship between epiblast cellular morphology and its pluripotency is not well understood. Here, using chicken epiblast and mammalian pluripotency stem cell (PSC) models, we show that PSCs undergo a mesenchymal-epithelial transition (MET) prior to EMT-associated pluripotency loss. Epiblast MET and its subsequent EMT are two distinct processes. The former, a partial MET, is associated with reversible initiation of pluripotency exit, whereas the latter, a full EMT, is associated with complete and irreversible pluripotency loss. We provide evidence that integrin-mediated cell-matrix interaction is a key player in pluripotency exit regulation. We propose that epiblast partial MET is an evolutionarily conserved process among all amniotic vertebrates and that epiblast pluripotency is restricted to an intermediate cellular state residing between the fully mesenchymal and fully epithelial states.

The Moderating Role of Sleep Quality on the Association between Neuroticism and Frontal Executive Function in Older Adults.

OBJECTIVE/BACKGROUND: Personality traits are regarded as risk factors for cognitive impairment in older adults, while sleep disturbance and physical inactivity are also considered as modifiable risk factors. Therefore, it could be beneficial to investigate the effects of those modifiable risk factors on the relationship between personality traits and cognitive functions, to prepare appropriate strategies for mitigating cognitive impairment. PARTICIPANTS: A total of 155 cognitively unimpaired older adults were included. METHODS: All participants underwent cognitive function tests using the Seoul Neuropsychological Screening Battery and examinations for personality traits using the Big Five Inventory. Individual physical activity and sleep quality were assessed using the International Physical Activity Questionnaire and Pittsburgh Sleep Quality Index, respectively. A hierarchical linear multiple regression analysis was performed to demonstrate the direct association between personality traits and cognitive functions, and the multiple moderator analysis was used to analyze the moderating effects of lifestyle factors on this association. RESULTS: Among the five personality traits, only neuroticism was negatively associated with the frontal executive and visuospatial functions after controlling age, sex, and years of education. Interestingly, the negative relationship between neuroticism and frontal executive function was alleviated in older adults with higher sleep quality. CONCLUSIONS: Our findings demonstrated that higher sleep quality has significant moderating effects on the negative association between neuroticism and frontal executive functions in older adults, which suggests intervention for improving sleep quality such as cognitive behavioral therapy can be considered in older adults who have personality traits associated with a high risk of cognitive impairment.

Hyaluronic Acid-Decorated Glycol Chitosan Nanoparticles for pH-Sensitive Controlled Release of Doxorubicin and Celecoxib in Nonsmall Cell Lung Cancer.

Nonsmall cell lung cancer (NSCLC) is a leading cause of global cancer mortality. Recently, combinatorial treatment approaches have shown promise as they better address tumor heterogeneity. However, drug pharmacokinetics and tissue distribution differences remain problematic. To overcome these issues and improve therapeutic efficacies, the use of nanomedicines has been suggested. We devised a CD44 receptor target hyaluronic acid (HA)-decorated glycol chitosan (GC) nanoparticle which is conjugated to doxorubicin (DOX) by a pH-sensitive linker and coloaded celecoxib (CXB; HA-GC-DOX/CXB). Successful chemical conjugation of GC to DOX was confirmed and HA-GC-DOX/CXB showed ∼150 nm of uniform spherical shape. HA-GC-DOX/CXB were stable at pH 7.4 but steadily increased in size and released drugs at pH 6.0 and 4.0. In vitro NSCLC cells showed that DOX and CXB combination therapy has synergism in both free drug and nanoparticle formulation. In vivo NSCLC xenograft mice showed DOX and CXB exhibited a synergistic tumor suppressive effect in HA-GC-DOX/CXB. Furthermore, HA-GC-DOX/CXB dramatically inhibited tumor growth compared to other treatments as well as suppressed inflammation and metastasis-related gene/protein in the tumor tissues. Our findings demonstrate HA-GC-DOX/CXB is a potential anticancer therapy that controlled release under acidic tumor microenvironments and enhanced CD44 overexpressed tumor target efficacy.

Noninvasive Early Detection of Calpain 2-Enriched Non-Small Cell Lung Cancer Using a Human Serum Albumin-Bounded Calpain 2 Nanosensor.

Lung cancer is diagnosed at an advanced stage due to its unrecognized symptoms, resulting in high mortality. In recent decades, research into the development of an early diagnostic method for lung cancer has expanded in order to overcome the high mortality rate. Calpain 2 (CAPN2) has been suggested as a tumor marker linked to angiogenesis, cell proliferation, and migration in non-small cell lung cancer. In this study, CAPN2 enzyme-activatable near-infrared peptide sensor linked to human serum albumin (HSA-CAPN2) was developed. Intracellular localization and strong recovered fluorescence signals of HSA-CAPN2 were observed in in vitro experiments using A549-Luc cells, and signal recovery was inhibited by ALLN (a CAPN2 inhibitor). In vivo distribution and signal recovery evaluations performed using A549-Luc cell xenograft mice revealed that HSA-CAPN2 accumulated in the tumor region and produced high fluorescent signal recovery. Three-dimensional reconstructed images using single-plane illumination microscopy after tissue clarity visualized localization of HSA-CAPN2 in tumors. In addition, ALLN pretreatment showed a significant inhibitory effect on signal recovery of HSA-CAPN2, and that inhibition was induced by downregulation of CAPN2 at the gene and protein levels followed by decreases in Ca2+ levels. Overall, the results demonstrate the potential of HSA-CAPN2 as a sensor for CAPN2-enriched cancer.

Preparation of Biodegradable PLGA-Nanoparticles Used for pH-Sensitive Intracellular Delivery of an Anti-inflammatory Bacterial Toxin to Macrophages.

Poly(D,L-lactide-co-glycolic) acid (PLGA) is a synthetic copolymer that has been used to design micro/nanoparticles as a carrier for macromolecules, such as protein and nucleic acids, that can be internalized by the endocytosis pathway. However, it is difficult to control the intracellular delivery to target organelles. Here we report an intracellular delivery system of nanoparticles modified with bacterial cytotoxins to the endoplasmic reticulum (ER) and anti-inflammatory activity of the nanoparticles. Subtilase cytotoxin (SubAB) is a bacterial toxin in certain enterohemorrhagic Escherichia coli (EHEC) strains that cleaves the host ER chaperone BiP and suppresses nuclear factor-kappaB (NF-κB) activation and nitric oxide (NO) generation in macrophages at sub-lethal concentration. PLGA-nanoparticles were modified with oligo histidine-tagged (6 × His-tagged) recombinant SubAB (SubAB-PLGA) through a pH-sensitive linkage, and their translocation to the ER in macrophage cell line J774.1 cells, effects on inducible NO synthase (iNOS), and levels of tumor necrosis factor (TNF)-α cytokine induced by lipopolysaccharide (LPS) were examined. Compared with free SubAB, SubAB-PLGA was significantly effective in BiP cleavage and the induction of the ER stress marker C/EBP homologous protein (CHOP) in J774.1 cells. Furthermore, SubAB-PLGA attenuated LPS-stimulated induction of iNOS and TNF-α. Our findings provide useful information for protein delivery to macrophages and may encourage therapeutic applications of nanoparticles to the treatment of inflammatory diseases.

Glycol Chitosan-Docosahexaenoic Acid Liposomes for Drug Delivery: Synergistic Effect of Doxorubicin-Rapamycin in Drug-Resistant Breast Cancer.

Marine ecosystems are the most prevalent ecosystems on the planet, providing a diversity of living organisms and resources. The development of nanotechnology may provide solutions for utilizing these thousands of potential compounds as marine pharmaceuticals. Here, we designed a liposomal glycol chitosan formulation to load both doxorubicin (DOX) and rapamycin (RAPA), and then evaluated its therapeutic potential in a prepared drug-resistant cell model. We explored the stability of the drug delivery system by changing the physiological conditions and characterized its physicochemical properties. The electrostatic complexation between DOX-glycol chitosan and docosahexaenoic acid RAPA-liposomes (GC-DOX/RAPA ω-liposomes) was precisely regulated, resulting in particle size of 131.3 nm and zeta potential of -14.5 mV. The well-characterized structure of GC-DOX/RAPA ω-liposomes led to high loading efficiencies of 4.1% for DOX and 6.2% for RAPA. Also, GC-DOX/RAPA ω-liposomes exhibited high colloidal stability under physiological conditions and synergistic anti-cancer effects on DOX-resistant MDA-MB-231 cells, while showing pH-sensitive drug release behavior. Our results provided a viable example of marine pharmaceuticals with therapeutic potential for treating drug-resistant tumors using an efficient and safe drug delivery system.

Commentary on: Increased stiffness of omental arteries from late pregnant women at advanced maternal age.

Worldwide, pregnancy at age 35 or older, termed 'advanced maternal age (AMA)', is increasing exponentially. As the incidence of pregnancy at AMA has increased, a growing body of evidence has suggested that AMA is also associated with increased risk for adverse maternal and fetal outcomes outside of genetic anomalies. Importantly, despite the mounting evidence and the increased global risk of adverse perinatal outcomes observed, few studies have examined the potential mechanisms underlying this elevated risk in pregnant people ≥35 years of age. Wooldridge and colleagues begin to address this gap in the literature. In their recent report, they examine vessel stiffness in omental resistance vessels obtained from pregnant individuals ≥35 years of age compared with pregnant individuals <35 years of age. Omental arteries were isolated and assessed via pressure myography (mechanical properties) and histological analysis for collagen and elastin content. Overall, the findings from this investigation report that maternal resistance arteries collected from women of AMA were less compliant and had less elastin than arteries obtained from women <35 years of age, suggesting that maternal resistance vessel stiffening in AMA may contribute to increased risk of adverse pregnancy outcomes. The authors should be commended for completing these studies in human resistance vessels, which now open new avenues for investigation and provoke a cascade of questions related to maternal cardiovascular adaptations to pregnancy in women ≥35 years of age.

Emerging role and promise of nanomaterials in organoid research.

Organoids are 3D stem cell-derived self-organization of cells. Organoid bioengineering helps recreate and tailor their architecture in vitro to generate mini organ-like properties, providing the opportunity to study fundamental cell behavior in heterogeneous populations and as a tool to model various diseases. Nanomaterials (NMs) are becoming indispensable in regenerative medicine and in developing treatment modalities for various diseases. Therefore, organoid-NM interactions are set to gain traction for the development of advanced diagnostics and therapeutics. Here, we discuss the interactions of NMs with distinctive organoid types, organoid matrices, trafficking and cargo delivery, organs-on-a-chip, bioprinting, downstream therapeutic implications, and future approaches.

Potential anticancer effect of aspirin and 2'-hydroxy-2,3,5'-trimethoxychalcone-linked polymeric micelles against cervical cancer through apoptosis.

Although early diagnosis and treatment of cancers in women are achievable through continuous diagnostic tests, cervical cancer (CVC) still has a high mortality rate. In the present study, we investigated whether certain nanoparticles (NPs), comprising aspirin conjugated 2'-hydroxy-2,3,5'-trimethoxychalcone chemicals, could induce the apoptosis of cancer cells. HeLa cells were treated with NPs and the cell viability was evaluated using WST-1 assay. Protein expression of Ki-67 was measured using immunocytochemistry. In addition, the apoptotic effect of NPs was determined using TUNEL assay. To investigate the apoptosis signaling pathways, reverse transcription quantitative PCR was performed and lipid accumulation was observed via holotomographic microscopy. The IC50 value of the NPs was 4.172 µM in HeLa cells. Furthermore, 10 µM NPs significantly inhibited the cell proliferation and stimulated the apoptosis of HeLa cells. In addition, apoptosis and mitochondrial dysfunction were induced by the NPs through lipid accumulation in HeLa cells, leading to apoptotic signaling cascades. Taken together, the results from the present study demonstrated that the NPs developed promoted apoptosis though efficient lipid accumulation in HeLa cells, suggesting that they may provide a novel way to improve the efficacy of CVC anticancer treatment.

Biomimetic Bacterial Membrane Vesicles for Drug Delivery Applications.

Numerous factors need to be considered to develop a nanodrug delivery system that is biocompatible, non-toxic, easy to synthesize, cost-effective, and feasible for scale up over and above their therapeutic efficacy. With regards to this, worldwide, exosomes, which are nano-sized vesicles obtained from mammalian cells, are being explored as a biomimetic drug delivery system that has superior biocompatibility and high translational capability. However, the economics of undertaking large-scale mammalian culture to derive exosomal vesicles for translation seems to be challenging and unfeasible. Recently, Bacterial Membrane Vesicles (BMVs) derived from bacteria are being explored as a viable alternative as biomimetic drug delivery systems that can be manufactured relatively easily at much lower costs at a large scale. Until now, BMVs have been investigated extensively as successful immunomodulating agents, but their capability as drug delivery systems remains to be explored in detail. In this review, the use of BMVs as suitable cargo delivery vehicles is discussed with focus on their use for in vivo treatment of cancer and bacterial infections reported thus far. Additionally, the different types of BMVs, factors affecting their synthesis and different cargo loading techniques used in BMVs are also discussed.

Psychometric properties of the Disturbing Dream and Nightmare Severity Index-Korean version.

STUDY OBJECTIVES: This study aimed to examine psychometric properties of the Disturbing Dream and Nightmare Severity Index (DDNSI) in individuals aged between 18 and 39. METHODS: All participants (n = 674) were asked to complete the DDNSI, including the modified Nightmare Effects Survey. Additionally, 109 participants were tested for test-retest reliability after 3 months. Among our sample, 229 (33.9%) reported having at least 1 nightmare per month. RESULTS: Internal consistency was evaluated for the total sample (Cronbach's α = .920) and separately for individuals reporting more than once per month (Cronbach's α = .755). Test-retest reliability after 3 months was .705. Convergent validity of the DDNSI with Nightmare Effects Survey was also satisfactory (r = .638, P < .001). Finally, exploratory factor analysis was conducted to explore the construct of the DDNSI, and results indicated that it consisted of 2 factors, nightmare frequency and nightmare distress [χ²(df) = 2.241(1) ∆χ² (∆df) = 155.575(4), Tucker-Lewis incremental fit index = .980, root mean square error of approximation (90% confidence interval) = .074 (0, .208), standardized root-mean-square residual = .011]. CONCLUSIONS: The DDNSI is a reliable measure of nightmare severity that can be used in various settings.

pH-sensitive multi-drug liposomes targeting folate receptor ß for efficient treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of lung cancer-related deaths worldwide. Tumor-associated macrophages (TAMs), which can be polarized into tumor-promoting M2 phenotype, overexpress folate receptor beta (FRß) and are associated with poor prognosis in NSCLC. In addition, calpain-2 (CAPN2) is overexpressed in NSCLC and is involved in tumor growth. To improve the anticancer efficacy of drugs and reduce their side effects in the treatment of NSCLC, it is important to develop smart drug delivery systems with specific targeting ability and controlled release mechanisms. In this study, FRß-targeted pH-sensitive liposomes were designed as carriers to ensure efficient drug delivery and acid-responsive release in NSCLC cells. Folate-mediated targeting of FRß in M2 TAMs and NSCLC cells effectively inhibited tumor growth and the stimulus-responsive drug release reduced the toxic side effects of the drug. The combination of doxycycline (anti-CAPN2) and docetaxel (anticancer drug) showed a synergistic inhibitory effect on tumor growth by suppressing CAPN2 expression.

Near Infrared Light Triggered Photo/Immuno-Therapy Toward Cancers.

Nanomaterials-based phototherapies, mainly including photothermal therapy (PTT), photodynamic therapy (PDT) and photoimmunotherapy (PIT), present high efficacy, minimal invasion and negligible adverse effects in cancer treatment. The integrated phototherapeutic modalities can enhance the efficiency of cancer immunotherapy for clinical application transformation. The near-infrared (NIR) light source enables phototherapies with the high penetration depth in the biological tissues, less toxic to normal cells and tissues and a low dose of light irradiation. Mediated via the novel NIR-responsive nanomaterials, PTT and PDT are able to provoke cancer cells apoptosis from the generated heat and reactive oxygen species, respectively. The released cancer-specific antigens and membrane damage danger signals from the damaged cancer cells trigger immune responses, which would enhance the antitumor efficacy via a variety of immunotherapy. This review summarized the recent advances in NIR-triggered photo-/immune-therapeutic modalities and their synergistic mechanisms and applications toward cancers. Furthermore, the challenges, potential solutions and future directions of NIR-triggered photo-/immunotherapy were briefly discussed.

Combined Aerobic and Resistance Training for Peak Oxygen Uptake, Muscle Strength, and Hypertrophy After Coronary Artery Disease: a Systematic Review and Meta-Analysis.

Maximal aerobic capacity measured as peak oxygen consumption (VO2peak), muscle strength, and muscle hypertrophy are the potent predictors of survival after coronary artery disease (CAD). The purpose of this study was to review the effects of combined aerobic training (AT) and resistance training (RT) on the three outcomes in CAD patients. Five electronic databases were searched. Combined AT and RT trials in 21 studies had a significantly greater favorable effect on all three outcomes compared with control groups (CON). In subgroup analyses for VO2peak, longer session duration and shorter post-CAD period were associated with larger effect size (ES). For muscle strength, higher training volume, longer post-CAD period, and younger age were associated with larger ES. In hypertrophy, longer training duration was associated with larger ES. Moderate intensity, 2-3 days per week, 50 min (AT), three sets of 10-12 repetitions, and seven exercises (RT) for 14 weeks are recommended.

Platelet-Like Gold Nanostars for Cancer Therapy: The Ability to Treat Cancer and Evade Immune Reactions.

The cell membrane-coating strategy has opened new opportunities for the development of biomimetic and multifunctional drug delivery platforms. Recently, a variety of gold nanoparticles, which can combine with blood cell membranes, have been shown to provide an effective approach for cancer therapy. Meanwhile, this class of hybrid nanostructures can deceive the immunological system to exhibit synergistic therapeutic effects. Here, we synthesized red blood cell (RBC) and platelet membrane-coated gold nanostars containing curcumin (R/P-cGNS) and evaluated whether R/P-cGNS had improved anticancer efficacy. We also validated a controlled release profile under near-infrared irradiation for the ability to target melanoma cells and to have an immunomodulatory effect on macrophages. RBC membrane coating provided self-antigens; therefore, it could evade clearance by macrophages, while platelet membrane coating provided targetability to cancer cells. Additionally, the nutraceutical curcumin provided anticancer and anti-inflammatory effects. In conclusion, the results presented in this study demonstrated that R/P-cGNS can deliver drugs to the target region and enhance anticancer effects while avoiding macrophage phagocytosis. We believe that R/P-cGNS can be a new design of the cell-based hybrid system for effective cancer therapy.

Near-Infrared Light-Triggered Photodynamic Therapy and Apoptosis Using Upconversion Nanoparticles With Dual Photosensitizers.

Elucidation of upconversion nanoparticles (UCNPs) that can be excited by near-infrared (NIR) light is an interesting topic in the field of photodynamic therapy (PDT). However, the PDT efficiency of conventional UCNPs is limited due to the low quantum yield and overheating effect of the 980 nm light source. In this study, a light source with a wavelength of 808 nm was used as an excitation source for Nd-doped UCNPs to solve the overheating effect. UCNPs with a core@shell structure (NaYF4:Yb,Er,Nd@NaYF4:Yb,Nd) were synthesized to increase the upconversion emission efficiency. Dual-color emitting Er-doped UCNPs and dual photosensitizers (Chlorin e6 and Rose Bengal) were used for enhanced PDT. Each photosensitizer could absorb red and green emissions of the UCNPs to generate reactive oxygen species (ROS), respectively. The ROS generation in a dual photosensitizer system is significantly higher than that in a single photosensitizer system. Additionally, PDT induces immunogenic apoptosis. In this study, by utilizing a highly efficient PDT agent, PDT-induced apoptosis was studied by biomarker analysis.

Development of ErbB2-Targeting Liposomes for Enhancing Drug Delivery to ErbB2-Positive Breast Cancer.

ErbB2 is a type of receptor tyrosine kinase, which is known to be involved in tumorigenesis, tumor aggressiveness, and clinical outcome. ErbB2-targeting therapy using therapeutic antibodies has been successful in breast cancer treatment. However, the need for repeated treatments and the high cost are major disadvantages with monoclonal antibody therapies. Compared with antibodies, peptides are cheap, relatively stable, and have low immunogenicity. We have developed a highly specific cancer-targeting drug delivery system using a targeting peptide to maximize the therapeutic efficiency of rapamycin and to help prevent drug resistance in ErbB2-positive breast cancer. Physicochemical characterization confirmed the successful construction of ErbB2-targeting liposomes (ErbB2Lipo). A comparison of a scrambled peptide (ScrErbB2) with the ErbB2-targeting peptide confirmed that these peptides had similar properties except for the targeting ability. The ErbB2Lipo exhibited higher delivery efficiency in ErbB2 positive BT-474 cells than non-targeting liposomes conjugated with ScrErbB2 (ScrErbB2Lipo). This peptide-targeting strategy has the potential to improve the efficacy of chemotherapy in ErbB2-positive cancers.

Fluorogenic Probe for Detecting Active Matrix Metalloproteinase-3 (MMP-3) in Plasma and Peripheral Blood Neutrophils to Indicate the Severity of Rheumatoid Arthritis.

Diagnosis of patients with rheumatoid arthritis (RA) is essential for early and accurate drug treatment to protect the patient from joint bone erosion and relieve symptoms of the disease. In some cases, the RA patient's X-ray images and other clinical diagnostic methods are often difficult to distinguish from different diseases, such as gout, osteoarthritis, and other inflammatory conditions. Thus, methods for diagnosis of disease activity and real-time monitoring of therapeutic effect and accurate differentiation from other bone diseases are needed. In this article, we suggest a matrix metalloproteinase-3 (MMP-3)-specific protease-activated probe immobilized in vitro kit and cell staining for flow cytometry analysis as methods to support clinical diagnosis. To overcome interindividual differences, we used phorbol 12-myristate 13-acetate (PMA)-activated plasma from 269 RA patients, 49 osteoarthritis patients, and 30 healthy volunteers. The in vitro kit developed for PMA-activated plasma showed potential for identifying disease severity and distinguishing RA from other bone diseases. In particular, expression of active MMP-3 increased until the moderate disease activity and then sharply decreased at severe disease. We suggest an analysis of intracellular MMP-3-specific protease-activated probe staining by flow cytometry. Compared with anti-MMP-3 antibody staining, the results for active MMP-3 in neutrophils using the probe exactly matched the results obtained with the in vitro kit. We also confirmed that expression of active MMP-3 was mainly from neutrophils. Together, these results suggest that the MMP-3-specific protease-activated probe might be a promising noninvasive tool for accurate diagnosis of disease severity and differentiation from similar bone diseases as well as for monitoring therapeutic efficacy.

The effects of exercise on vascular endothelial function in type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Vascular endothelial dysfunction induced by hyperglycemia and elevated insulin resistance is a potent risk factor for cardiovascular disease and likely contributes to multiple chronic disease complications associated with aging. The aim of this study was to systematically review and quantify the effects of exercise on endothelial function (EF) in type 2 diabetes (T2D). METHODS: Five electronic databases were searched (until June 2017) for studies that met the following criteria: (i) randomized controlled trials; (ii) T2D aged ≥ 18 years; (iii) measured EF by brachial artery flow-mediated dilation (FMD); (iv) structured and supervised exercise intervention for ≥ 8 weeks. RESULTS: Thirteen cohorts, selected from eight studies (306 patients, average age 59 years), met the inclusion criteria. Exercise training significantly increased FMD (mean ES = 0.41, 95% CI 0.21-0.62, P < 0.001). Low to moderate intensity subgroups and aerobic exercise (AE) subgroups significantly increased FMD more than moderate to high intensity subgroups and combined AE and resistance exercise subgroups respectively (P < 0.01, P < 0.05). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessments reported that quality of evidence for all outcomes was moderate except shear rate showing low. Egger's test showed no significant publication bias for all outcomes. CONCLUSION: Our results suggest that in patients with T2D, lower intensity exercise has physiological meaningful effects on EF, in support of the emerging concept that the lower efforts of exercise are not necessarily less cardioprotective than higher intensity training.

Perceived Interpersonal Burdensomeness as a Mediator between Nightmare Distress and Suicidal Ideation in Nightmare Sufferers.

Previous studies have supported the significant association between nightmares and suicidal ideation, but the underlying mechanisms are largely unknown. The purpose of the present study was to investigate perceived burdensomeness and thwarted belongingness as mediators in the relationship between nightmare distress and suicidal ideation. This sample consisted of 301 undergraduate students who endorsed experiencing nightmares (mean age 21.87 ± 2.17, 78.1% female). All participants completed questionnaires on nightmare distress (Nightmare Distress Questionnaire), unmet interpersonal needs (Interpersonal Needs Questionnaire), and suicidal ideation (Depressive Symptom Inventory - Suicidality Subscale). Analyses were performed using multiple mediation regression. Results indicated that nightmare distress was associated with perceived burdensomeness (r = 0.17, p < 0.001) and suicidal ideation (r = 0.24, p < 0.001), but was not related to thwarted belongingness (r = 0.10, p = 0.06). Multiple mediation analyses revealed that perceived burdensomeness partially mediated the relationship between nightmares and suicidal ideation, but thwarted belongingness did not. Additionally, this mediating relationship for perceived burdensomeness was moderated by gender, being significant only for females. These findings highlight the important role of interpersonal factors in the relationship between nightmares and suicidal ideation.