Impairment in acquisition of conditioned fear in people with depressive symptoms.

Background: Depression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored. Methods: We used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response. Results: The findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms. Conclusion: The study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems.

Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering.

Engineered heart tissues (EHTs) are regarded as being the most promising alternative to synthetic materials, and autologous mesenchymal stem cells (MSCs) are widely used as seeding cells. However, few studies have evaluated the feasibility of using MSCs from patients with cyanotic congenital heart disease (C-CHD) as seeding cells for EHTs, in comparison with cells from patients of acyanotic congenital heart disease (A-CHD). In the present study, we cultured MSCs from A-CHD and C-CHD patients in normoxia or hypoxia conditions, and compared their pro-angiogenic, anti-apoptotic and inflammation-modulatory potentials. In vivo, we seeded the cells into collagen patches conjugated with, or without, proangiogenic cytokines, which were used to repair the right ventricular outflow tract (RVOT) of rats. The in vitro results showed that C-CHD MSCs expressed higher levels of VEGFA and VEGFR2, and secreted more pro-angiogenic and anti-inflammatory cytokines under hypoxic conditions. On the other hand, apoptosis-related genes from C-CHD MSCs were modulated adaptably, converting these cells into an anti-apoptotic phenotype. In vivo studies demonstrated that in 4 weeks after RVOT reconstruction, cytokine-immobilized patches seeded with C-CHD MSCs exhibited preserved morphology, prolonged cell survival and enhanced angiogenesis compared to A-CHD MSCs. C-CHD MSCs that undergo "naturally hypoxic precondition" present a better cell source for EHTs, which would provide a promising individualized biomaterial for C-CHD patients.

Comparison of adipose­ and bone marrow­derived stem cells in protecting against ox­LDL­induced inflammation in M1­macrophage­derived foam cells.

Adipose­derived stem cells (ADSCs) and bone marrow­derived stem cells (BMSCs) are considered to be prospective sources of mesenchymal stromal cells (MSCs), that can be used in cell therapy for atherosclerosis. The present study investigated whether ADSCs co­cultured with M1 foam macrophages via treatment with oxidized low­density lipoprotein (ox­LDL) would lead to similar or improved anti­inflammatory effects compared with BMSCs. ADSCs, peripheral blood monocytes, BMSCs and ox­LDL were isolated from ten coronary heart disease (CHD) patients. After three passages, the supernatants of the ADSCs and BMSCs were collected and systematically analysed by liquid chromatography­quadrupole time­of­flight­mass spectrometry (6530; Agilent Technologies, Inc., Santa Clara, CA, USA). Cis­9, trans­11 was deemed to be responsible for the potential differences in the metabolic characteristics of ADSCs and BMSCs. These peripheral blood monocytes were characterized using flow cytometry. Following peripheral blood monocytes differentiation into M1 macrophages, the formation of M1 foam macrophages was achieved through treatment with ox­LDL. Overall, 2x106 ADSCs, BMSCs or BMSCs+cis­9, trans­11 were co­cultured with M1 foam macrophages. Anti­inflammatory capability, phagocytic activity, anti­apoptotic capability and cell viability assays were compared among these groups. It was demonstrated that the accumulation of lipid droplets decreased following ADSCs, BMSCs or BMSCs+cis­9, trans­11 treatment in M1 macrophages derived from foam cells. Consistently, ADSCs exhibited great advantageous anti­inflammatory capabilities, phagocytic activity, anti­apoptotic capability activity and cell viability over BMSCs or BMSCs+cis­9, trans­11. Additionally, BMSCs+cis­9, trans­11 also demonstrated marked improvement in anti­inflammatory capability, phagocytic activity, anti­apoptotic capability activity and cell viability in comparison with BMSCs. The present results indicated that ADSCs would be more appropriate for transplantation to treat atherosclerosis than BMSCs alone or BMSCs+cis­9, trans­11. This may be an important mechanism to regulate macrophage immune function.

Artesunate Protects Against Sepsis-Induced Lung Injury Via Heme Oxygenase-1 Modulation.

Artesunate, a derivative of artemisinin, has anti-inflammatory properties and exerts protective roles in sepsis. Heme oxygense-1 (HO-1) inhibits the inflammatory response through reduction of proinflammatory cytokines and leukocyte influx into tissues. The present study investigated the effects of artesunate on HO-1 and septic lung injury. Cecal ligation and puncture (CLP) was employed to induce septic lung injury. Mice pretreated with artesunate (AS) (15 mg/kg) exhibited decreased sepsis-induced mortality and lung injury and alleviated lung pathological changes and neutrophil infiltration. In addition, AS lowered the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum and bronchoalveolar lavage fluid (BALF) and inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase isoform (iNOS) expression and NF-κB activation in lung tissue. In addition, AS enhanced NF-E2-related factor-2 (Nrf2) activation and HO-1 expression and enzymatic activity in lung tissue. However, the protective effects of AS on sepsis-induced lung injury were eliminated by ZnPP IX, an HO-1 competitive inhibitor. Therefore, AS plays protective roles in septic lung injury related to the upregulation of HO-1. These findings suggest an effective and applicable treatment to sepsis-induced lung injury and provide new insights into the molecular mechanisms and actions of AS.