Luteolin ameliorates pentetrazole-induced seizures through the inhibition of the TLR4/NF-κB signaling pathway.

Epilepsy represents a prevalent neurological disorder in the population, and the existing antiepileptic drugs (AEDs) often fail to adequately control seizures. Inflammation is recognized as a pivotal factor in the pathophysiology of epilepsy. Luteolin, a natural flavonoid extract, possesses anti-inflammatory properties and exhibits promising neuroprotective activity. Nevertheless, the precise molecular mechanisms underlying the antiepileptic effects of luteolin remain elusive. In this study, we established a rat model of epilepsy using pentylenetetrazole (PTZ) to induce seizures. A series of behavioral experiments were conducted to assess behavioral abilities and cognitive function. Histological techniques, including HE staining, Nissl staining, and TUNEL staining, were employed to assess hippocampal neuronal damage. Additionally, Western blotting, RT-qPCR, and ELISA were utilized to analyze the expression levels of proteins involved in the TLR4/IκBα/NF-κB signaling pathway, transcription levels of apoptotic factors, and levels of inflammatory cytokines, respectively. Luteolin exhibited a dose-dependent reduction in seizure severity, prolonged the latency period of seizures, and shortened seizure duration. Furthermore, luteolin prevented hippocampal neuronal damage in PTZ-induced epileptic rats and partially restored behavioral function and learning and memory abilities. Lastly, PTZ kindling activated the TLR4/IκBα/NF-κB pathway, leading to elevated levels of the cytokines TNF-α, IL-6 and IL-1ß, which were attenuated by luteolin. Luteolin exerted anticonvulsant and neuroprotective activities in the PTZ-induced epileptic model. Its mechanism was associated with the inhibition of the TLR4/IκBα/NF-κB pathway, alleviating the immune-inflammatory response in the post-epileptic hippocampus.

Nicotinamide mononucleotide alleviates seizures via modulating SIRT1-PGC-1α mediated mitochondrial fusion and fission.

Both human and animal experiments have demonstrated that energy metabolism dysfunction in neurons after seizures is associated with an imbalance in mitochondrial fusion/fission dynamics. Effective neuronal mitochondrial dynamics regulation strategies remain elusive. Nicotinamide mononucleotide (NMN) can ameliorate mitochondrial functional and oxidative stress in age-related diseases. But whether NMN improves mitochondrial energy metabolism to exert anti-epileptic effects is unclear. This study aims to clarify if NMN can protect neurons from pentylenetetrazole (PTZ) or Mg2+ -free-induced mitochondrial disorder and apoptosis via animal and cell models. We established a continuous 30-day PTZ (37 mg/kg) intraperitoneal injection-induced epileptic mouse model and a cell model induced by Mg2+ -free solution incubation to explore the neuroprotective effects of NMN. We found that NMN treatment significantly reduced the seizure intensity of PTZ-induced epileptic mice, improved their learning and memory ability, and enhanced their motor activity and exploration desire. At the same time, in vitro and in vivo experiments showed that NMN can inhibit neuronal apoptosis and improve the mitochondrial energy metabolism function of neurons. In addition, NMN down-regulated the expression of mitochondrial fission proteins (Drp1 and Fis1) and promoted the expression of mitochondrial fusion proteins (Mfn1 and Mfn2) by activating the SIRT1-PGC-1α pathway, thereby inhibiting PTZ or Mg2+ -free extracellular solution-induced mitochondrial dysfunction, cell apoptosis, and oxidative stress. However, combined intervention of SIRT1 inhibitor, Selisistat, and PGC-1α inhibitor, SR-18292, eliminated the regulatory effect of NMN pre-treatment on mitochondrial fusion and fission proteins and apoptosis-related proteins. Therefore, NMN intervention may be a new potential treatment for cognitive impairment and behavioral disorders induced by epilepsy, and targeting the SIRT1-PGC-1α pathway may be a promising therapeutic strategy for seizures.

Advances in the phytochemistry and pharmacology of plant-derived phthalides.

Phthalides are a class of unique compounds such as ligustilide, butylphthalide and butyldenephthalide, which have shown to possess multiple bioactivities in new drug research and development. Phthalides are naturally distributed in different plants that have been utilized as herbal treatments for various ailments with a long history in Asia, Europe and North America. Their extensive biological activity has led to a dramatic increase in the study of phthalide compounds in recent years. This review summarizes the latest research progress of plant-derived phthalides, and a total of 133 phthalide compounds are described based on the characteristics of chemical structures. Pharmacological properties of plant-derived phthalides are associated with hemorheological improvement, vascular function modulation and central nervous system protection. Potential treatments for a variety of diseases mainly including cardio-cerebrovascular disorders and neurological complications such as Alzheimer's disease are also concluded. In addition, key metabolic pathways have been clearly elucidated. Further investigations on the molecular mechanisms involved in biological activity are recommended for offering new insights into profound comprehension of phthalide applications.

miR-122-5p Restrains Pancreatic Cancer Cell Growth and Causes Apoptosis by Negatively Regulating ASCT2.

BACKGROUND/AIM: System ASC amino acid transporter-2 (ASCT2) is abnormally highly expressed in tumor cells and closely associated with a poor prognosis, but the regulatory mechanism of abnormally high ASCT2 expression is scarcely investigated. MicroRNAs (miRNAs) that are abnormally expressed regulate gene expression to have either oncogenic or tumor-suppressive effects in pancreatic cancer (PC). MicroRNA-122-5p (miR-122-5p) dysregulation has been seen in various cancer entities, but the biological function of miR-122-5p in PC and its regulation mechanisms remain unknown. MATERIALS AND METHODS: Western blot and quantitative RT-PCR were used to measure the expression of miR-122-5p, ASCT2, and apoptosis-related proteins. CCK-8 assays were used to elucidate the effect on cell proliferation. Flow cytometry (FCM) assays were utilized to evaluate cell apoptosis. A dual-luciferase reporter assay was utilized to determine if miR-122a-5p directly targeted ASCT2. Glutamine consumption and the α-ketoglutarate (α-KG) and adenosine triphosphate (ATP) contents were determined using respective assays. RESULTS: MiR-122-5p expression was low whereas ASCT2 expression was high in PC tissues and cells. Overexpressing miR-122-5p restrained pancreatic cancer cell proliferation, accelerated apoptosis, and decreased glutamine consumption, α-ketoglutarate (α-KG) production and ATP generation, whereas suppressing miR-122-5p had the opposite effect. Moreover, the reporter gene test established ASCT2 as a miR-122-5p target. Overexpression of miR-122-5p decreased ASCT2 expression, whereas miR-122-5p repression increased ASCT2 expression. In addition, miR-122-5p also regulated apoptosis-related pathways. CONCLUSION: MiR-122-5p may function as a tumor suppressor by inhibiting the proliferation, glutamine metabolism, and inducing apoptosis via altering the expression of ASCT2 in pancreatic cancer cells.

Potential analgesic effect of Foshousan oil-loaded chitosan-alginate nanoparticles on the treatment of migraine.

Background: Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine. Methods: FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug. Results: FSSO-loaded CS-AL NPs (212.1 ± 5.2 nm, 45.1 ± 6.2 mV) had a well-defined spherical shape with prolonged drug release and good storage within 4 weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15 µg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104 mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104 mg/kg) group. Conclusion: FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine.

Experience summary of a COVID-19 designated community hospital and its operation model.

The aim of this study was to summarize the administration model of a COVID-19 designated hospital transformed from a community hospital to improve the emergency capacity of community hospitals and the efficiency of diagnosis and treatment of medical staff in the COVID-19 pandemic. This study analyzed the surrounding environment, ward layout, area management, treatment process, medical staff, and patient management of the designated community hospital. From February 5, 2020, to February 18, 2020, the designated community hospital has received 198 COVID-19 mild and general patients (including 41 in the hospital at the beginning of the period). Among them, 39 were transferred to module hospitals, 131 were discharged, and 28 were in the hospital at the end of the period, and none of them became severe. There were 41 medical staff, and none of them had COVID-19 infection. We have achieved excellent results in the prevention and control stratagems implemented in this new community-designated hospital that specializes in treating patients with COVID-19. Its diagnosis and treatment model has completed the treatment of COVID-19 patients successfully. After adjustment, this community hospital can shoulder the critical task of being a designated hospital for COVID-19, which includes admission, isolation, and therapy of suspected and mild COVID-19 patients, reducing the medical burden of superior hospitals. Our experience provides concepts for community hospitals to temporarily undertake medical responsibilities to reduce the spread of COVID-19 during the pandemic.

Mycoplasma fermentans deacetylase promotes mammalian cell stress tolerance.

Mycoplasma fermentans is a pathogenic bacterium that infects humans and has potential pathogenic roles in respiratory, genital and rheumatoid diseases. NAD+-dependent deacetylase is involved in a wide range of pathophysiological processes and our studies have demonstrated that expression of mycoplasmal deacetylase in mammalian cells inhibits proliferation but promotes anti-starvation stress tolerance. Furthermore, mycoplasmal deacetylase is involved in cellular anti-oxidation, which correlates with changes in the proapoptotic proteins BIK, p21 and BIM. Mycoplasmal deacetylase binds to and deacetylates the FOXO3 protein, similar with mammalian SIRT2, and affects expression of the FOXO3 target gene BIM, resulting in inhibition of cell proliferation. Mycoplasmal deacetylase also alters the performance of cells under drug stress. This study expands our understanding of the potential molecular and cellular mechanisms of interaction between mycoplasmas and mammalian cells.

Social Smoking and Mental Health Among Chinese Male College Students.

PURPOSE: China has a high prevalence of smoking, but the characteristics of social smoking in Chinese college students have not been investigated. We examined the pattern of social smoking and explored the association between social smoking and personal cessation efforts and mental health factors among Chinese male college students. DESIGN: Study design was a cross-sectional survey. SETTING: P. R. China was the setting of the study. SUBJECTS: Participants were a random sample of 1327 male college students. MEASURES: All participants completed a self-administered questionnaire that examined their smoking behaviors and a group of specific mental health factors (loneliness, self-harm, suicide, depression, and anxiety). ANALYSIS: Analysis was conducted using descriptive statistics, χ2 analysis, and multivariate logistic regression. RESULTS: Of a total of 207 current smokers, 102 (49.3%) were identified as social smokers. Compared with nonsmokers, social smokers had increased risks for depression (odds ratio, 1.74; 95% confidence interval, 1.15-2.65). Among daily smokers, social smokers were less likely to have an intention to quit smoking than nonsocial smokers (odds ratio, .08; 95% confidence interval, .01-.57). CONCLUSION: This study reveals unique psychologic characteristics related to social smoking. College students are a particular group of interest because unhealthy behaviors initiated during adolescence may continue through adulthood. Our findings provide evidence for future tobacco control intervention among this population.