The role of ROS-pyroptosis in PM2.5 induced air-blood barrier destruction.

Fine particulate matter (PM2.5) has attracted increasing attention due to its health-threatening effects. Although numerous studies have investigated the impact of PM2.5 on lung injuries, the specific mechanisms underlying the damage to the air-blood barrier after exposure to PM2.5 remain unclear. In this study, we established an in vitro co-culture system using lung epithelial cells and capillary endothelial cells. Our findings indicated that the tight junction (TJ) proteins were up-regulated in the co-cultured system compared to the monolayer-cultured cells, suggesting the establishment of a more closely connected in vitro system. Following exposure to PM2.5, we observed damage to the air-blood barrier in vitro. Concurrently, PM2.5 exposure induced significant oxidative stress and activated the NLRP3 inflammasome-mediated pyroptosis pathway. When oxidative stress was inhibited, we observed a decrease in pyroptosis and an increase in TJ protein levels. Additionally, disulfiram reversed the adverse effects of PM2.5, effectively suppressing pyroptosis and ameliorating air-blood barrier dysfunction. Our results indicate that the oxidative stress-pyroptosis pathway plays a critical role in the disruption of the air-blood barrier induced by PM2.5 exposure. Disulfiram may represent a promising therapeutic option for mitigating PM2.5-related lung damage.

PM2.5 induce myocardial injury in hyperlipidemic mice through ROS-pyroptosis signaling pathway.

Exposure to particulate matters with diameters below 2.5 µm (PM2.5) is considered a major risk factor for cardiovascular diseases (CVDs). The closest associations between PM2.5 and CVDs have been observed in hyperbetalipoproteinemia cases, although the detailed underpinning mechanism remains undefined. In this work, hyperlipidemic mice and H9C2 cells were used to examine the effects of PM2.5 on myocardial injury and their underlying mechanisms. The results revealed that PM2.5 exposure caused severe myocardial damage in the high-fat mouse model. Oxidative stress and pyroptosis were also observed along with myocardial injury. After inhibiting pyroptosis with disulfiram (DSF), the level of pyroptosis was effectively reduced as well as myocardial injury, suggesting that PM2.5 induced the pyroptosis pathway and further caused myocardial injury and cell death. Afterwards, by suppressing PM2.5-induced oxidative stress with N-acetyl-L-cysteine (NAC), myocardial injury was markedly ameliorated, and the upregulation of pyroptosis markers was reversed, which indicated that PM2.5-pyroptosis was also improved. Taken together, this study revealed that PM2.5 induce myocardial injury through the ROS-pyroptosis signaling pathway in hyperlipidemia mice models, providing a potential approach for clinical interventions.

A high performance liquid chromatography tandem mass spectrometry protocol for detection of neurotransmitters in the rat brain tissue.

The detection of neurotransmitters has extensively been applied to the study of the pathogenesis, diagnosis, and therapeutic effect of drugs on many neuropsychiatric diseases. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been employed to determine neurotransmitters levels due to its distinct advantages. However, neurotransmitter detection still presents some challenges. A rapid and sensitive HPLC-MS/MS protocol has been established in our lab, which can simultaneously detect 5 neurotransmitters with an easy pretreatment procedure. The protocol provides demanded reference value for the lab using an Agilent HPLC-MS/MS system with a triple quadrupole analyzer.

Tryptophan Hydroxylase 2 Knockout Male Rats Exhibit a Strengthened Oxytocin System, Are Aggressive, and Are Less Anxious.

The central serotoninergic system is critical for stress responsivity and social behavior, and its dysregulations have been centrally implicated in virtually all neuropsychiatric disorders. Genetic serotonin depletion animal models could provide a tool to elucidate the causes and mechanisms of diseases and to develop new treatment approaches. Previously, mice lacking tryptophan hydroxylase 2 (Tph2) have been developed, showing altered behaviors and neurotransmission. However, the effect of congenital serotonin deficiency on emotional and social behavior in rats is still largely unknown, as are the underlying mechanisms. In this study, we used a Tph2 knockout (Tph2-/-) male rat model to study how the lack of serotonin in the rat brain affects anxiety-like and social behaviors. Since oxytocin is centrally implicated in these behaviors, we furthermore explored whether the effects of Tph2 knockout on behavior would relate to changes in the oxytocin system. We show that Tph2-/- rats display reduced anxiety-like behavior and a high level of aggression in social interactions. In addition, oxytocin receptor expression was increased in the infralimbic and prelimbic cortices, paraventricular nucleus, dorsal raphe nucleus, and some subregions of the hippocampus, which was paralleled by increased levels of oxytocin in the medial frontal cortex and paraventricular nucleus but not the dorsal raphe nucleus, central amygdala, and hippocampus. In conclusion, our study demonstrated reduced anxiety but exaggerated aggression in Tph2-/- male rats and reveals for the first time a potential involvement of altered oxytocin system function. Meanwhile, the research of oxytocin could be distinguished in almost any psychiatric disorder including anxiety and mental disorders. This research potentially proposes a new target for the treatment of such disorders, from a genetic serotonin deficiency aspect.

Oxidative stress activates Ryr2-Ca2+ and apoptosis to promote PM2.5-induced heart injury of hyperlipidemia mice.

The increased cases of hyperlipemia in China and the crucial role of PM2.5 in inducing and promoting cardiovascular diseases have attracting more and more researchers' attention. However, the effects and mechanisms of PM2.5 on cardiovascular system of hyperlipidemia people are still unclear. In this study, hyperlipidemia mice model was established by high-fat diet. Then we exposed these mice to PM2.5 or saline to explore the underling mechanism of cardiac injury in hyperlipidemia mice. The hyperlipemia mice are more susceptible to heart damage caused by PM2.5 exposure. The participation of oxidative stress, cell apoptosis and Ca2+ related mechanism could be observed in this model. After NAC (N-acetyl-L-cysteine) treatment, the oxidative stress level induced by PM2.5 exposure significantly decreased in hyperlipemia mice. NAC effectively alleviated cardiac injury, improved the imbalance of calcium and attenuated apoptosis induced by PM2.5 exposure in hyperlipemia mice. The strong oxidative stress in hyperlipemia mice could lead to calcium homeostasis imbalance and activation of apoptosis-related pathways. This mechanism of PM2.5-induced myocardial injury was also verified in vitro. In our present study, we demonstrated the contribution of the PM2.5-ROS-Ryr2-Ca2+ axis in PM2.5-induced heart injury of hyperlipidemia mice, offering a potential therapeutical target for related pathology.

Oxidative stress activates the TRPM2-Ca2+-NLRP3 axis to promote PM2.5-induced lung injury of mice.

PM2.5, a main particulate air pollutant, poses a serious hazard to human health. The exposure to PM2.5 increases mortality and morbidity of many respiratory diseases such as asthma, chronic obstructive pulmonary diseases and even lung cancer. The contribution of reactive oxygen species (ROS) in the PM2.5-induced acute lung injury process was confirmed in our previous research, but the molecular mechanism based for it remains unclarified. In this research, ROS-induced lung injury after exposure to PM2.5 was explored in vivo and in vitro. The in vivo study indicated that N-acetyl-L-cysteine (NAC) could attenuate the accumulation of inflammatory cells, the thickening of alveolar wall and the degree of lung injury. Furthermore, we found ROS could regulate the intracellular Ca2+ level, expression of the Transient Receptor Potential Melastatin 2 (TRPM2), NLRP3 and its downstream inflammatory factors in vivo. In vitro experiments with A549 cells and primary type II alveolar epithelium cells (SD cells) showed that ROS induced by PM2.5 exposure could mediate intracellular Ca2+ mobilization via TRPM2, with a subsequent activation of NLRP3. In our present study, we demonstrated the contribution of the ROS-TRPM2-Ca2+-NLRP3 pathway in PM2.5-induced acute lung injury and offered a potential therapeutical target valid for related pathology.

The harmful effects of acute PM2.5 exposure to the heart and a novel preventive and therapeutic function of CEOs.

Epidemiological researches have demonstrated the relationship between PM2.5 exposure and increased morbidity and mortality of cardiovascular injury. However, no effective therapeutic method was established. The purpose of this study is to investigate the effect of acute PM2.5 exposure on the mice heart tissue and explore the therapeutic effects of compound essential oils (CEOs) in this model. In this study, after mice were exposed to PM2.5 intratracheally, some obvious histopathological changes as well as some great alterations of proinflammatory cytokines were observed in the heart tissue. The imbalance of oxidative stress, the altered Ca2+ channel related proteins and the increased intracellular free Ca2+ were all involved in the heart impairment and would also be investigated in this model. The CEOs alleviated the heart impairment via its antioxidant effect rather than its anti-inflammatory function because our results revealed that oxidative stress related indicators were restored after CEOs administration. At the same time, increased concentration of intracellular free Ca2+ and ROS induced by PM2.5 were reduced after NAC (N-Acetyl-L-cysteine) administration. These data suggested that the acute PM2.5 exposure would damage heart tissue by inducing the inflammatory response, oxidative stress and intracellular free Ca2+ overload. PM2.5-induced oxidative stress probably increase intracellular free Ca2+ via RYR2 and SERCA2a. CEOs have the potential to be a novel effective and convenient therapeutic method to prevent and treat the acute heart impairment induced by PM2.5 via its antioxidant function.

Histamine-4 receptor antagonist JNJ7777120 inhibits pro-inflammatory microglia and prevents the progression of Parkinson-like pathology and behaviour in a rat model.

The activation of microglial cells is presumed to play a key role in the pathogenesis of Parkinson's disease (PD). The activity of microglia is regulated by the histamine-4 receptor (H4R), thus providing a novel target that may prevent the progression of PD. However, this putative mechanism has so far not been validated. In our previous study, we found that mRNA expression of H4R was upregulated in PD patients. In the present study, we validated this possible mechanism using the rotenone-induced PD rat model, in which mRNA expression levels of H4R-, and microglial markers were significantly increased in the ventral midbrain. Inhibition of H4R in rotenone-induced PD rat model by infusion of the specific H4R antagonist JNJ7777120 into the lateral ventricle resulted in blockade of microglial activation. In addition, pharmacological targeting of H4R in rotenone-lesioned rats resulted in reduced apomorphine-induced rotational behaviour, prevention of dopaminergic neuron degeneration and associated decreases in striatal dopamine levels. These changes were accompanied by a reduction of Lewy body-like neuropathology. Our results provide first proof of the efficacy of an H4R antagonist in a commonly used PD rat model, and proposes the H4R as a promising target to clinically tackle microglial activation and thereby the progression of PD.

[Jinleng undershorts palliates varicocele].

OBJECTIVE: To investigate the effect of Jinleng undershorts on the elevated scrotal temperature induced by varicocele as well as on other clinical symptoms of the disease. METHODS: Fifty-one varicocele patients received the treatment of wearing Jinleng undershorts for 30 min twice a day for a course of 90 days. Comparisons were made between the scrotal temperatures and other clinical symptoms of varicocele before and after the treatment. RESULTS: After 90 days of treatment with Jinleng undershorts, the left scrotal temperature of the varicocele patients was significantly reduced from (32.16 +/- 0.79) degrees C to (31.53 +/- 0.77) degrees C (P < 0.01), and the right scrotal temperature decreased from (31.91 +/- 0.73) degrees C to (31.81 +/- 0.63) degrees C (P > 0.05). Compared with pretreatment, significant improvement was found in such symptoms as wetness, fever and swelling of the scrotum, backache, headache, dizziness, fatigue and anxiety (P < 0.05), as well as in testicular pain (P < 0.01) and IIEF-5 score, which was increased from 15.89 +/- 6.13 to 20.04 +/- 3.87 (P < 0.01). CONCLUSION: Jinleng undershorts can be used for the treatment of mild and moderate varicocele.