Constraining the Symmetron Model with the HUST-2020 Torsion Pendulum Experiment.

The search for dynamically screening the coupling between the scalar field and matter in high-density environment is achievable with the symmetron model. The high-accuracy and short-range gravity experiment is proposed to test the symmetron model. In this Letter, the data of the HUST-2020 torsion pendulum experiment testing the inverse-square law at submillimeter range is analyzed to constrain the symmetron model. The results show that the HUST-2020 experiment is uniquely sensitive to probe the symmetron model with a mass scale of µ=7.2×10^{-3} eV, and the self-coupling parameter λ≲105 is excluded at mass scale M=0.3 TeV. Especially, at the dark energy scale µ=2.4×10^{-3} eV, the constraint at M=1.3 TeV is improved by about 10 times the previous constraints on the torsion pendulum experiment.

Possible repair mechanisms of renin-angiotensin system inhibitors, matrix metalloproteinase-9 inhibitors and protein hormones on methamphetamine-induced neurotoxicity.

Methamphetamine is a highly addictive central stimulant with extensive and strong neurotoxicity. The neurotoxicity of methamphetamine is closely related to the imbalance of dopamine levels and the destruction of the blood-brain barrier. An increase in dopamine may induce adverse effects such as behavioral sensitization and excessive locomotion. Damage to the blood-brain barrier can cause toxic or harmful substances to leak to the central nervous system, leading to neurotoxicity. The renin-angiotensin system is essential for the regulation of dopamine levels in the brain. Matrix metalloproteinase-9 causes reward effects and behavioral sensitization by inducing dopamine release. Prolactin has been shown to be involved in the regulation of tight junction proteins and the integrity of the blood-brain barrier. At present, the treatment of methamphetamine detoxification is still based on psychotherapy, and there is no specific medicine. With the rapid increase in global seizures of methamphetamine, the treatment of its toxicity has attracted more and more attention. This review intends to summarize the therapeutic mechanisms of renin-angiotensin inhibitors, matrix metalloproteinase-9 inhibitors and protein hormones (prolactin) on methamphetamine neurotoxicity. The repair effects of these three on methamphetamine may be related to the maintenance of brain dopamine balance and the integrity of the blood-brain barrier. This review is expected to provide the new therapeutic strategy of methamphetamine toxicity.

Tetrahydropalmatine Regulates BDNF through TrkB/CAM Interaction to Alleviate the Neurotoxicity Induced by Methamphetamine.

Tetrahydropalmatine (THP) has analgesic, hypnotic, sedative, and other pharmacological effects. Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, growth, and development. However, their mechanism of action in methamphetamine (MA)-induced neurotoxicity remains unclear. This study aims to explore the important role of BDNF in MA neurotoxicity and whether THP can regulate BDNF through the interaction between tyrosine kinase receptor B (TrkB)/calmodulin (CAM) to alleviate the neurotoxicity induced by MA. SD rats were randomly divided into control, MA, and MA + THP groups. Stereotyped behavior test, captive rejection test, open field test (OFT), and Morris water maze (MWM) were used to evaluate the anxiety, aggression, cognition, learning, and memory. Extracted hippocampus and mesencephalon tissue were detected by Western blot, HE staining, and immunohistochemistry. TUNEL staining was used to detect apoptosis. MOE was used for bioinformatics prediction, and coimmunoprecipitation was used to confirm protein interactions. Long-term abuse of MA resulted in lower weight gain ratio and nerve cell damage and caused various neurotoxicity-related behavioral abnormalities: anxiety, aggression, cognitive motor disorders, and learning and memory disorders. MA-induced neurotoxicity is related to the down-regulation of BDNF and apoptosis. THP attenuated the MA-induced neurotoxicity by decreasing CAM, increasing TrkB, phosphorylating Akt, up-regulating NF-κB and BDNF, and inhibiting cell apoptosis. MA can induce neurotoxicity in rats. BDNF may play a vital role in MA-induced neurotoxicity. THP regulates BDNF through TrkB/CAM interaction to alleviate the neurotoxicity induced by MA. THP may be a potential therapeutic drug for the neurotoxic and neurodegenerative diseases related to MA.

Levo-tetrahydropalmatine: A new potential medication for methamphetamine addiction and neurotoxicity.

Levo-tetrahydropalmatine (l-THP) is mainly derived from the dried tuber of the Papaveraceae plant Corydalis, also called Corydalis B, which is a drug with analgesic, hypnotic, sedative and other effects. Methamphetamine (METH) belongs to the central nervous stimulant and is a highly addictive drug. It is an urgent problem to study the mechanism of methamphetamine neurotoxicity and to search for the therapeutic targets of the METH addiction. This review is aimed to discuss the pharmacological mechanism and the protective effects of l-THP on METH-induced neurotoxicity, and to explore the therapeutic prospects of l-THP for METH addiction to provide an innovative application of l-THP in clinic. It was found that exposure to METH leads to the compulsive drug-seeking and drug-taking behavior, which is ultimately resulted in METH addiction and neurotoxicity. L-THP has the inhibitory effects on the incidence, maintenance and relapse of METH addiction. L-THP can effectively enhance the plasticity of nerve cells and improve the function of nerve cells where brain-derived neurotrophic factor (BDNF) and its pathways play a protective role. Therefore, l-THP has the potential to become an important therapeutic drug for METH addiction and neurotoxicity.

TBHQ-Overview of Multiple Mechanisms against Oxidative Stress for Attenuating Methamphetamine-Induced Neurotoxicity.

Methamphetamine is a derivative of amphetamines, a highly addictive central stimulant with multiple systemic toxicity including the brain, heart, liver, lung, and spleen. It has adverse effects such as apoptosis and breakdown of the blood-brain barrier. Methamphetamine is a fatal and toxic chemical substance, and its lethal mechanism has been widely studied in recent years. The possible mechanism is that methamphetamine can cause cardiotoxicity and neurotoxicity mainly by inducing oxidative stress so as to generate heat, eliminate people's hunger and thirst, and maintain a state of excitement so that people can continue to exercise. According to many research, there is no doubt that methamphetamine triggers neurotoxicity by inducing reactive oxygen species (ROS) production and redox imbalance. This review summarized the mechanisms of methamphetamine-induced neurotoxicity including apoptosis and blood-brain barrier breakdown through oxidative stress and analyzed several possible antioxidative mechanisms of tert-butylhydroquinone (TBHQ) which is a kind of food additive with antioxidative effects. As a nuclear factor E2-related factor 2 (Nrf2) agonist, TBHQ may inhibit neurotoxicity caused by oxidative stress through the following three mechanisms: the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, the astrocytes activation, and the glutathione pathway. The mechanism about methamphetamine's toxic effects and its antioxidative therapeutic drugs would become a research hotspot in this field and has very important research significance.

Resveratrol protects the integrity of alveolar epithelial barrier via SIRT1/PTEN/p-Akt pathway in methamphetamine-induced chronic lung injury.

OBJECTIVES: SIRT1 is an antioxidative factor, but its mechanism in methamphetamine (MA)-induced lung injury remains unclear. The purpose of this study is to determine whether MA can disrupt the integrity of alveolar epithelial barrier, whether SIRT1 is involved in MA-induced chronic lung injury and whether Resveratrol (Res) can protect the integrity of alveolar epithelial cells by regulating ROS to activate SIRT1/PTEN/p-Akt pathway. MATERIALS AND METHODS: The rats were randomly divided into control group and MA group. Extracted lungs were detected by Western blot, HE staining and immunohistochemistry. The alveolar epithelial cells were treated with MA or/and Res, following by Western blot, LDH leakage assay and flow cytometry. MOE is used for bio-informatics prediction. RESULTS: Chronic exposure to MA can cause slower growth ratio of weight, increased RVI and induced lung injury including the reduced number of alveolar sacs and the thickened alveolar walls. MA-induced apoptosis was associated with SIRT1-related oxidative stress. Res suppressed ROS levels, activated SIRT1, negatively regulated PTEN, phosphorylated Akt, reduced LDH leakage, increased the expression of ZO-1 and E-cadherin and inhibited the apoptosis of alveolar epithelial cells to attenuate MA-induced higher permeability of alveolar epithelium. CONCLUSIONS: MA disrupted the integrity of alveolar epithelial barrier. Res inhibited oxidative stress and reversed MA-induced higher permeability and apoptosis of alveolar epithelium by the activation of SIRT1/PTEN/p-Akt pathway.

Chronic toxicity of methamphetamine: Oxidative remodeling of pulmonary arteries.

Methamphetamine (MA) has a high uptake in lung, but the precise mechanism of MA-induced lung toxicity remains unclear. The aim of this study is to investigate the role of MA abuse in remodeling of pulmonary arteries and to explore the possible correlation of the association of the remodeling with the redox imbalance in pulmonary arterial smooth muscle cells (PASMCs). Wistar rats were randomly divided into control group and MA group for the experimental study. We employed H&E staining, western blot, immunofluorescence, knockdown, flow in our experimental approach. Our studies shows that chronic exposure to MA led to weight loss, increased pulmonary arterial pressure, hypertrophy of right ventricle and remodeling of pulmonary arterial wall of rats. Our cell culture study with PASMCs indicates that MA significantly induced the imbalance between proliferation and apoptosis by upregulating the level of PCNA, Bcl-2 and reduction in the expression of BAX and Caspase 3. MA markedly prevented the nuclear translocation of Nrf2 to inhibit antioxidation. The knockdown of Nrf2 expression using siRNA significantly elevated the expression of SOD2/GCS and the production of ROS in PASMCs and even scaled up the amount of PASMCs induced by MA. Linear regression analysis showed that knockdown of Nrf2 promoted the positive correlation of relative ROS level with proliferation of PASMCs. Therefore, chronic exposure to MA induces pulmonary arterial remodeling by Nrf2-mediated imbalance of redox system to aggravate oxidative stress, and Nrf2 is a possible target for the treatment of MA-lung toxicity.