Sustained TNF signaling is required for the synaptic and anxiety-like behavioral response to acute stress.

Acute stress triggers plasticity of forebrain synapses as well as behavioral changes. Here we reveal that Tumor Necrosis Factor α (TNF) is a required downstream mediator of the stress response in mice, necessary for stress-induced synaptic potentiation in the ventral hippocampus and for an increase in anxiety-like behaviour. Acute stress is sufficient to activate microglia, triggering the long-term release of TNF. Critically, on-going TNF signaling specifically in the ventral hippocampus is necessary to sustain both the stress-induced synaptic and behavioral changes, as these could be reversed hours after induction by antagonizing TNF signaling. This demonstrates that TNF maintains the synaptic and behavioral stress response in vivo, making TNF a potential novel therapeutic target for stress disorders.

Diagnostic accuracy of prostate-specific antigen below 4 ng/mL as a cutoff for diagnosing prostate cancer in a hospital setting: A systematic review and meta-analysis.

PURPOSE: A prostate-specific antigen (PSA) cutoff of 4 ng/mL has been widely used for prostate cancer screening in population-based settings. However, the accuracy of PSA below 4 ng/mL as a cutoff for diagnosing prostate cancer in a hospital setting is inconclusive. We systematically reviewed the accuracy of PSA below 4 ng/mL cutoff in a hospital setting. MATERIALS AND METHODS: We systematically reviewed the literature by searching major databases until March 2020, and a meta-analysis and quality assessment were performed. RESULTS: A total of 11 studies were included at the completion of the screening process. The meta-analysis showed a sensitivity of 0.92 and a specificity of 0.16 for a PSA cutoff below 4 ng/mL. The area under the hierarchical summary receiver operating characteristic curve was 0.87, the positive likelihood ratio was 1.23, the negative likelihood ratio was 0.46, and the diagnostic odds ratio was 2.64. PSA sensitivities and specificities varied according to the cutoff range: 0.94 and 0.17 for 2 to 2.99 ng/mL, and 0.92 and 0.16 for 3 to 3.99 ng/mL, respectively. No significant differences in the sensitivity and specificity of PSA cutoffs in the range of 2 to 2.99 ng/mL and 3 to 3.99 ng/mL were found. CONCLUSIONS: Although a PSA cutoff <3 ng/mL is relatively more sensitive and specific than PSA ≥3 ng/mL, no significant differences in sensitivity and specificity were found in the diagnosis of prostate cancer. Therefore, clinicians should choose an appropriate PSA cutoff on the basis of clinical circumstances and patients' characteristics.

Retroviral expression of arginine decarboxylase attenuates oxidative burden in mouse cortical neural stem cells.

Neural stem cells (NSCs) have the potential to integrate seamlessly into the host tissues, and the development of potential stem cells resistant to stress injury is an elusive goal for efficient therapeutic application. Oxidative injury induces cellular and nuclear damages and the balanced regulation of reactive oxygen species is of critical significance for stem cell development, function, and survival. Agmatine, an endogenous primary amine and a novel neuromodulator synthesized from the decarboxylation of l-arginine catalyzed by arginine decarboxylase (ADC), has been reported to possess neuroprotective properties. In the present study, we determined whether the expression of ADC in NSCs can prevent the cells from oxidative injury. Retrovirus expressing human (ADC), (vhADC) was generated using a pLXSN vector. Cortical NSCs were infected with vhADC and subjected to H2O2 injury (200 µM for 15 h). Reverse transcriptase-polymerase chain reaction and immunocytochemical staining revealed that hADC mRNA and protein were highly expressed in the vhADC-infected NSCs (ADC-NSCs). High performance liquid chromatography (HPLC) analysis confirmed high concentration of agmatine in the ADC-NSCs, when exposed to H2O2 injury. Lactate dehydrogenase leakage and intracellular reactive oxygen species formation were about 2-fold reduced in ADC-NSCs when compared with control NSCs and NSCs infected with mock vector (P < 0.05). DNA fragmentation, chromatin condensation, and expression of apoptotic proteins such as p53, bax, and caspase-3 cleavage were significantly decreased in ADC-NSCs (P < 0.05), suggesting the prevention of apoptotic cell death following H2O2 injury. Our study demonstrates that overexpression of ADC is an effective novel approach to protect stem cells from oxidative damage.

Adsorption of mesenchymal stem cells and cortical neural stem cells on carbon nanotube/polycarbonate urethane.

BACKGROUND & AIM: Carbon nanotubes (CNTs) are a promising material for implantation due to the fact that CNTs are conductive and have nanostructured dimensions that mimic the 3D structure of proteins found in extracellular matrices. We have investigated whether the CNTs interact with various types of stem cells and either selectively enhance survival of stem cells or not. MATERIALS & METHODS: CNTs used in the experiments are aligned with polycarbonate urethane. Experiments were carried out using mesenchymal stem cells (MSCs) and cortical derived neurospheres. Immunocytochemistry and scanning electron microscopic analysis were performed for determining the favorable surface material (either CNT or polycarbonate urethane array) for cell survival. RESULTS: It was demonstrated that the MSCs and the neurosphere of cortex-derived neural stem cells (NSCs) grew on the CNT array and both MSCs and NSCs interacted with the aligned CNTs. The results suggest that CNTs assist in the proliferation of MSCs and aid differentiation of cortex-derived NSCs. CONCLUSION: CNTs may be a novel biocompatible nanophase material with the potential for aiding neuron differentiation.