Alzheimer’s disease (AD), a progressive neurodegenerative disease characterized by impairments of cognitive function as a result of synaptic deficits and neuronal loss, is associated with inflammation. Apelin-13, a predominant neuropeptide with inhibiting effect on inflammation, has beneficial effects on cognition memory and neuronal damage. However, whether apelin-13 can protect neurons to ameliorate cognitive deficits in AD by inhibiting the inflammatory response remains largely unknown. To test this hypothesis, rats were intracerebroventricularly (ICV) injected with streptozotocin (3 mg/kg) alone or in combination with apelin-13 (2 μg). And tyrosine receptor kinase B (TrkB) blocker K252a (200 nM) was administrated 10 min before apelin injection. Furthermore, cognitive performance was assessed by new object recognition (NOR) and Y-maze tests. Protein expression of apelin, APJ, microglial marker (IBA1), astroglia marker (GFAP), interleukin 1 beta (IL-1β), tumor necrosis factor-α (TNF-α), synaptophysin (SYP), brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB) in the hippocampus were examined by western blotting or immunohistochemistry. And the gene expression of IBA1, GFAP, IL-1β, TNF-α, and SYP were detected by real-time quantitative polymerase chain reaction (PCR). Inflammatory disorder in the hippocampus was tested by hematoxylin and eosin (H&E) staining. The enzyme-linked immunosorbent assay (ELISA) was used to study the expression level of acetylcholine. And the activity of acetylcholinesterase was detected by Acetylcholinesterase Assay Kit. We observed that apelin/APJ signaling was downregulated in the hippocampus of rats administrated with STZ. Apelin-13 was found to significantly ameliorate STZ-induced AD-like phenotypes including congnitive deficit, cholinergic disfunction and the damage of neuron and synaptic plasticity. Moreover, apelin-13 inhibited microglia and astrocyte activation, reduced IL-1β and TNF-α expression and hippocampal BDNF/TrkB expression deficit in AD rats. Finally, apelin-13-mediated effects were blocked by TrkB receptor antagonist K252a. These results suggest that apelin-13 upregulates BDNF/TrkB pathway against cognitive deficit in a STZ-induced rat model of sporadic AD by attenuating inflammation.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and healthcare burden worldwide. The progression of COPD is a combination of genetic predisposition and environmental factors, primarily cigarette smoking, and the underlying mechanisms are still unknown. Intestinal microecology impacts host immunity, metabolism, and resistance to pathogenic infections, which may be involved in pulmonary disease. Moreover, substantial interaction occurs between the intestinal and respiratory immune niches. After reviewing nearly 500 articles, we found the gut-lung axis plays an important role in the development of COPD. COPD patients often have dysbiosis of the intestinal microenvironment, which can affect host immunity through a series of mechanisms, exacerbating or protecting against COPD progression. This paper summarizes how the gut-lung axis influences COPD, including the alterations of intestinal microecology, the pathological mechanisms, and the involved immune responses. Finally, we summarize the latest research advances in COPD treatment from the perspective of regulating the gut-lung axis and intestinal immunity and evaluate the potential value of the gut-lung axis in improving COPD prognosis.

Chronic persistent airway inflammation has been associated with the comorbidity of asthma and bipolar disorder (BD). However, the direct relevance between airway inflammation and BD-like psychiatric comorbidity is almost unknown. Integrin β4 (ITGB4) is downregulated on the airway epithelial of asthma patients, which might play a critical role in the parthenogenesis of airway inflammation. So this study aimed to examine the role of ITGB4 deficiency in mediating airway inflammation and further leading to the BD-like behaviors. ITGB4^−/− mice were generated by mating ITGB4^fl/fl mice with CCSP–rtTA^tg/−/TetO-Cretg/tg mice. Mania-like behavior tests were performed, including hyperlocomotion, d-amphetamine-induced hyperactivity, open-field test, and elevated plus-maze test. Depressive-like behavior tests were carried out, including sucrose preference, forced swimming, and learned helplessness. Inflammatory cells (Th17, Th1, Th2) in the lung were examined by flow cytometry. Futhermore, inflammatory cytokines (IL-4, IL-13) in bronchoalveolar lavage fluid and sera were detected by ELISA. Protein expression of the IL-4Rα on choroid plexus, microglial marker (IBA1), and synapse-associated proteins (synaptophysin, SYP) in the hippocampus and prefrontal cortex were examined by western blotting. Additionally, proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in the hippocampus and prefrontal cortex were detected by immunohistochemistry. Inflammatory disorder in the lung, hippocampus, and prefrontal cortex was tested by hematoxylin and eosin (H&E) staining. And cell apoptosis in the hippocampus and prefrontal cortex was measured by TUNEL test. ITGB4^−/− mice exhibited mania-like behavior, including hyperlocomotion, d-amphetamine-induced hyperactivity, and reduced anxiety-like behavior. While under stressful conditions, ITGB4^−/− mice manifested depressive-like behavior, including anhedonia, behavioral despair, and enhanced learned helplessness. At the same time, ITGB4^−/− mice mainly exerted Th2-type inflammation in periphery, like the number and major cytokines IL-4 and IL-13 of Th2-type inflammation. ITGB4^−/− mice also showed a significant increase of microglia and pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in the hippocampus and prefrontal cortex. Additionally, neuron damage, increased neuron apoptosis, and the decrease of SYP were found in ITGB4^−/− mice. These findings confirmed that airway inflammatory induced by ITGB4 deficiency is the important incentive for the BD-like behavior during asthma pathogenesis. The ITGB4-deficient mice provide a validated animal model for us to study the possible mechanism of BD-like psychiatric comorbidity of asthma patients.

The mortality rate of idiopathic pulmonary fibrosis (IPF) increases yearly due to ineffective treatment. Given that the lung is exposed to the external environment, it is likely that oxidative stress, especially the stimulation of DNA, would be of particular importance in pulmonary fibrosis. DNA damage is known to play an important role in idiopathic pulmonary fibrosis initiation, so DNA repair systems targeting damage are also crucial for the survival of lung cells. Although many contemporary reports have summarized the role of individual DNA damage and repair pathways in their hypotheses, they have not focused on idiopathic pulmonary fibrosis. This review, therefore, aims to provide a concise overview for researchers to understand the pathways of DNA damage and repair and their roles in IPF.

Oxidative stress induced by hypoxia/ischemia resulted in the excessive reactive oxygen species (ROS) and the relative inadequate antioxidants. As the initial barrier to environmental pollutants and allergic stimuli, airway epithelial cell is vulnerable to oxidative stress. In recent years, the antioxidant effect of hydrogen sulfide (H₂S) has attracted much attention. Therefore, in this study, we explored the impact of H₂S on CoCl₂-induced cell injury in 16HBE14o- cells. The effect of CoCl₂on the cell viability was detected by Cell Counting Kit (CCK-8) and the level of ROS in 16HBE14o- cells in response to varying doses (100–1000μmol/L) of CoCl₂(a common chemical mimic of hypoxia) was measured by using fluorescent probe DCFH-DA. It was shown that, in 16HBE14o- cells, CoCl₂acutely increased the ROS content in a dose-dependent manner, and the increased ROS was inhibited by the NaHS (as a donor of H₂S). Moreover, the calcium ion fluorescence probe Fura-2/AM and fluorescence dye Rh123 were used to investigate the intracellular calcium concentration ([Ca²⁺]i) and mitochondria membrane potential (MMP) in 16HBE14o- cells, respectively. In addition, we examined apoptosis of 16HBE14o- cells with Hoechst 33342. The results showed that the CoCl₂effectively elevated the Ca²⁺influx, declined the MMP, and aggravated apoptosis, which were abrogated by NaHS. These results demonstrate that H₂S could attenuate CoCl₂-induced hypoxia injury via reducing ROS to perform an agonistic role for the Ca²⁺influx and MMP dissipation.

Diagnosis of tuberculous meningitis (TBM) remains a challenge. This study aimed to evaluate the performance of T-SPOT.TB test on cerebrospinal fluid mononuclear cells (CSFMCs) for suspected TBM patients. 43 consecutive patients with suspected TBM were enrolled in the study from June 2011 to September 2014. T-SPOT.TB was performed on both CSFMCs and peripheral blood mononuclear cells (PBMCs). The final diagnosis of TBM was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on CSFMCs and PBMCs were analyzed. Of the 43 patients, 12 (27.9%) were finally diagnosed with TBM, 28 (65.1%) with non-TBM, and 3 (7.0%) with indeterminate diagnoses. Of 40 cases with definite diagnoses, the sensitivity and specificity were 92.0% and 96.0% for T-SPOT.TB on CSFMCs, and 83.0% and 82.0% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on CSFMCs were 85.0% and 96.0%, respectively. The PPV and NPV were 67.0% and 92.0% for T-SPOT.TB on PBMCs. The difference of T-SPOT.TB between CSFMCs and PBMCs was not significant so far as sensitivity, specificity, PPV, and NPV were concerned (P>0.05 for each). However, T-SPOT.TB on CSFMC and CSFMC: PBMC in TBM cases seemed higher than that in non-TBM cases. Our study further showed that T-SPOT.TB on CSFMCs might be a rapid and accurate diagnostic test for TBM. CSFMC: PBMC T-SPOT.TB ratio might be useful for the early diagnosis of TBM.