Reversible and Turn-On Fluorescence Detection of Phosphate in Aqueous Solution and Living Cell Imaging by Supramolecular Metallacycles with AIE-Active Ligands.

Luminescent supramolecular metallacycles have attracted great interest as a new promising class of sensing substrates. In this work, two tetraphenylethene (TPE)-based diimidazole and dipyrazole ligands with the aggregation-induced emission (AIE) feature were designed for the construction of supramolecular tetragonal metallacycles 1-4 with two 90° mononuclear [(bpy)M]2+ or dinuclear [(bpy)2M2]4+ acceptors (bpy = 2,2'-dipyridine; M = Pd, Pt), in which the fluorescence can be quenched to an "off" state due to the ligand-to-metal charge transfer (LMCT). Metallacycle 1 was utilized as a fluorescence sensor for phosphate (PO43-) detection in aqueous solution by means of disassembly, leading to the release of the ligand. Additionally, the metallacycle can be regenerated through self-assembly via the introduction of Pd(II) acceptors. PO43- was detected using TPE-based metallacycles over a wide concentration range, with a detection limit as low as 2.1 × 10-8 M. Furthermore, sensor 1 also presented the semiquantitative visual detection ability for PO43- in the test paper mode via fluorescence changes. The aforementioned studies not only enhance the current research on fluorescent materials but also offer a strategy for the creation of stimuli-responsive supramolecular coordination complexes.

Levomilnacipran ameliorates lipopolysaccharide-induced depression-like behaviors and suppressed the TLR4/Ras signaling pathway.

Levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, has been reported to have anti-depressive effects. However, the detailed mechanisms underlying these effects are still unclear. This study aimed to investigate the antidepressant mechanisms of levomilnacipran to discover new perspectives on the treatment of depression in male rats. Intraperitoneal injection of lipopolysaccharide (LPS) was used to induce depressive behaviors in rats. Activation of microglia and apoptosis of neurons verified by immunofluorescence. Inflammatory related proteins and neurotrophic related proteins were verified by immunoblotting. The mRNA expression of apoptosis markers was verified by real-time quantitative PCR. Finally, electron microscopy analysis was used to observe the ultrastructural pathology of neuron. Here, we found that the anti-depression and anti-anxiety effects of levomilnacipran in the LPS-induced rat model of depression was resulted from the suppression of neuroinflammation and neuronal apoptosis within prefrontal cortex of rats. Furthermore, we found that levomilnacipran could decrease the number of microglia and suppress its activation in prefrontal cortex of rats. This effect may be mediated by suppressing the TLR4/NF-κB and Ras/p38 signaling pathways. In addition, levomilnacipran plays a neuroprotective role by increasing the expression of neurotrophic factors. Taken together, these results suggest that levomilnacipran exerts antidepressant effects by attenuating neuroinflammation to inhibit the damage in central nervous system and plays a neuroprotective role to improve depressive behaviors. These findings suggest that suppression of neuroinflammation in prefrontal cortex could ameliorate depressive behavioral disorder of rats induced by LPS, which provided a new perspective for the treatment of depression.

[M8L4]8+-Type Squares Self-Assembled by Dipalladium Corners and Bridging Aromatic Dipyrazole Ligands for Iodine Capture.

Square-like metallamacrocyclic palladium(II) complexes [M8L4]8+ (1-7) were synthesized by reacting aromatic dipyrazole ligands (H2L1-H2L3 with pyromellitic arylimide-, 1,4,5,8-naphthalenetetracarboxylic arylimide-, and anthracene-based aromatic groups, respectively) with dipalladium corners ([(bpy)2Pd2(NO3)2](NO3)2, [(dmbpy)2Pd2(NO3)2](NO3)2, or [(phen)2Pd2(NO3)2](NO3)2, where bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine, and phen = 1,10-phenanthroline) in aqueous solutions via metal-directed self-assembly. Metallamacrocycles 1-7 were fully characterized by 1H and 13C nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry, and the square structure of 7·8NO3- was further confirmed via single crystal X-ray diffraction. These square-like metallamacrocycles exhibit effective performance for iodine adsorption.

Correction: Self-assembly of tripyrazolate-linked [M6L2] cages for the selective sensing of HSO3- and gaseous SO2 by turn-on fluorescence.

Correction for 'Self-assembly of tripyrazolate-linked [M6L2] cages for the selective sensing of HSO3- and gaseous SO2 by turn-on fluorescence' by Peipei Wang et al., Dalton Trans., 2023, https://doi.org/10.1039/d3dt00083d.

Self-assembly of tripyrazolate-linked [M6L2] cages for the selective sensing of HSO3- and gaseous SO2 by turn-on fluorescence.

Owing to their structural designability and tuneable properties, supramolecular metal-organic complexes have recently emerged as promising candidates for the sensing and detection of molecules and anions. Herein, we synthesised three tripyrazolate-linked [M6L2] metallocages with the formulas [(bpyPd)6L2](NO3)6 (1), [(dmbpyPd)6L2](NO3)6 (2), and [(phenPd)6L2](NO3)6 (3) (H3L = tris(4-(5-(trifluoromethyl)-1H-pyrazol-3-yl)phenyl)amine, bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethylbipyridine, phen = 1,10-phenanthroline). Crystallography revealed that metal-directed coordination and the bidentate chelate behaviour of the ligand induced the self-assembly of supramolecular metal-organic cages. Notably, these cages were employed as turn-on fluorescence sensors for SO2 and its derivative (HSO3-) through a disassembly mechanism. Cages 1, 2, and 3 showed a highly selective and sensitive detection of HSO3- over other common anions in aqueous solutions and of SO2 gas over other common gasses, with an excellent anti-interference ability. These metallocages were subsequently applied as sensors in environmental and biological samples. This study not only enriches the ongoing research on metal-organic supramolecular materials but also facilitates the future preparation of stimuli-responsive supramolecular coordination complexes.

Hippocampal microRNA-26a-3p deficit contributes to neuroinflammation and behavioral disorders via p38 MAPK signaling pathway in rats.

BACKGROUND: Neuronal injury is considered a critical risk factor in the pathogenesis of most neurological and neuropsychiatric diseases. However, the underlying molecular mechanisms and identification of potential therapeutic targets for preventing neuronal injury associated with brain function remain largely uncharacterized. Therefore, identifying neural mechanisms would put new insights into the progression of this condition and provide novel therapeutic strategies for the treatment of these diseases. METHODS: Stereotactic injection of AAV virus was used to knock-down the miR-26a-3p within hippocampus of rats. Behavioral changes was detected by open field test (OFT), elevated plus maze (EPM), forced swim test (FST) and sucrose preference test (SPT). The inflammatory cytokines and related proteins were verified by real-time quantitative PCR, immunoblotting or immunofluorescence assay. Golgi staining and electron microscopy analysis was used to observe the dendritic spine, synapse and ultrastructural pathology. SB203580 (0.5 mg/kg) were administered daily to prevent p38 MAPK via an intraperitoneal (i.p.) injection. Finally, electrophysiological method was used to examine the synaptic transmission via whole-cell patch-clamp recording. RESULTS: Here, we showed that miR-26a-3p deficiency within hippocampal regions leads to the activation of microglia, increased level of pro-inflammatory cytokines and behavioral disorders in rats, effects which appear to be mediated by directly targeting the p38 mitogen-activated protein kinase (MAPK)-NF-κB signaling pathway. Specifically, we found that the enhanced glia-activation may consequently result in neuronal deterioration that mainly presented as the dysregulation of structural and functional plasticity in hippocampal neurons. In contrast, preventing p38 pathway by SB203580 significantly ameliorated abnormal behavioral phenotypes and neuronal jury resulting from miR-26a-3p knock-down. CONCLUSION: These results suggest that the normal expression of miR-26a-3p exerts neuroprotective effects via suppressing neural abnormality and maintaining neuroplasticity to against behavioral disorders in rats. These effects appear to involve a down-regulation of p38 MAPK-NF-κB signaling within the hippocampal region. Taken together, these findings provide evidence that miR-26a-3p can function as a critical factor in regulating neural activity and suggest that the maintaining of normal structure and function of neurons might be a potential therapeutic strategy in the treatment of neurological disorders.

Stress-induced reduction of Na+/H+ exchanger isoform 1 promotes maladaptation of neuroplasticity and exacerbates depressive behaviors.

Major depression disorder (MDD) is a neuropsychiatric disorder characterized by abnormal neuronal activity in specific brain regions. A factor that is crucial in maintaining normal neuronal functioning is intracellular pH (pHi) homeostasis. In this study, we show that chronic stress, which induces depression-like behaviors in animal models, down-regulates the expression of the hippocampal Na+/H+ exchanger isoform 1, NHE1, a major determinant of pHi in neurons. Knockdown of NHE1 in CA1 hippocampal pyramidal neurons leads to intracellular acidification, promotes dendritic spine loss, lowers excitatory synaptic transmission, and enhances the susceptibility to stress exposure in rats. Moreover, E3 ubiquitin ligase cullin4A may promote ubiquitination and degradation of NHE1 to induce these effects of an unbalanced pHi on synaptic processes. Electrophysiological data further suggest that the abnormal excitability of hippocampal neurons caused by maladaptation of neuroplasticity may be involved in the pathogenesis of this disease. These findings elucidate a mechanism for pHi homeostasis alteration as related to MDD.

Pharmacokinetic evaluation and relative bioavailability pilot study of fidaxomicin in healthy Chinese subjects: An open, randomized, single-dose, cross-over study.

OBJECTIVE: To compare the pharmacokinetic (PK) characteristics, investigate relative bioavailability, and provide data for potential additional bioequivalence trials between generic fidaxomicin (test (T) formulation) and the original brand (reference (R) formulation) in healthy Chinese subjects. MATERIALS AND METHODS: An open, randomized, single-dose, cross-over study was conducted in 18 healthy Chinese subjects. The subjects randomly received T or R formulations and the alternative formulations were received after a 14-day wash-out period. Blood and fecal samples were collected and tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK parameters were calculated using a non-compartmental model. Relative bioavailability considering commonly established bioequivalence criteria was assessed. RESULTS: Cmax were 3.58 ± 2.74 ng/mL and 6.01 ± 3.93 ng/mL, and AUC0-∞ were 35.71 ± 18.68 h×ng/mL and 52.15 ± 31.31 h×ng/mL for the T and R formulations, respectively. The tmax of both formulations was 5.00 hours. The cumulative fecal excretion rate (Fe0-96h/F) of fidaxomicin and its main active metabolite OP-1118 were similar for both formulations. The geometric mean ratios and 90% confidence intervals (CI) of AUC0-t, AUC0-∞, and Cmax were not completely within the range of 80.00 - 125.00%. Significant within-subject and inter-subject coefficients of variation (> 30%) were found. CONCLUSION: Despite the differences in exposure, PK characteristics and fecal recovery of the two formulations were similar, suggesting that an effective concentration of the generic fidaxomicin could be achieved locally in the gastrointestinal tract. Fidaxomicin was a highly viable drug, thus providing reference for future clinical study design.

A Pattern to Link Adenosine Signaling, Circadian System, and Potential Final Common Pathway in the Pathogenesis of Major Depressive Disorder.

Several studies have reported separate roles of adenosine receptors and circadian clockwork in major depressive disorder. While less evidence exists for regulation of the circadian clock by adenosine signaling, a small number of studies have linked the adenosinergic system, the molecular circadian clock, and mood regulation. In this article, we review relevant advances and propose that adenosine receptor signaling, including canonical and other alternative downstream cellular pathways, regulates circadian gene expression, which in turn may underlie the pathogenesis of mood disorders. Moreover, we summarize the convergent point of these signaling pathways and put forward a pattern by which Homer1a expression, regulated by both cAMP-response element binding protein (CREB) and circadian clock genes, may be the final common pathogenetic mechanism in depression.

Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway.

BACKGROUND: Agomelatine has been shown to be effective in the treatment of depression, but the molecular mechanisms underlying its antidepressant effects have yet to be elucidated. Identification of these molecular mechanisms would not only offer new insights into the basis for depression but also provide the foundation for the development of novel treatments for this disorder. METHODS: Intraperitoneal injection of LPS was used to induce depression-like behaviors in rats. The interactions of the 5-HT2C reporter and Gαi-2 were verified by immunoprecipitation or immunofluorescence assay. Inflammatory related proteins, autophagy related proteins and apoptosis markers were verified by immunoblotting or immunofluorescence assay. Finally, electron microscopy analysis was used to observe the synapse and ultrastructural pathology. RESULTS: Here, we found that the capacity for agomelatine to ameliorate depression and anxiety in a lipopolysaccharide (LPS)-induced rat model of depression was associated with an alleviation of neuroinflammation, abnormal autophagy and neuronal apoptosis as well as the promotion of neurogenesis in the hippocampal dentate gyrus (DG) region of these rats. We also found that the 5-HT2C receptor is coupled with G alphai (2) (Gαi-2) protein within hippocampal neurons and, agomelatine, acting as a 5-HT2C receptor antagonist, can up-regulate activity of the Gαi-2-cAMP-PKA pathway. Such events then suppress activation of the apoptosis signal-regulating kinase 1 (ASK1) pathway, a member of the mitogen-activated protein kinase (MAPK) family involved in pathological processes of many diseases. CONCLUSION: Taken together, these results suggest that agomelatine plays a neuroprotective role in regulating neuroinflammation, autophagy disorder and apoptosis in this LPS-induced rat model of depression, effects which are associated with the display of antidepressant behaviors. These findings provide evidence for some of the potential mechanisms for the antidepressant effects of agomelatine.

Highly specific and selective fluorescent chemosensor for sensing of Hg(II) by NH-pyrazolate-functionalized AIEgens.

Luminescent organic molecules are of important realistic significance to the human health and ecological environment due to their fascinating applications. Here we report the design and synthesis of luminescent organic-molecules by introducing two or four NH-pyrazolate groups as mercury-binding moieties to aromatic cores. Interestingly, the new aromatic tetraphenylene-bridged multi-NH-pyrazoles exhibit strong fluorescence in both aggregate and solid state and constitutes highly selective proof-of-concept luminescent sensor for Hg(II) ion among various competitive transition-metal ions in both organic and mixed solutions via metal-nitrogen binding. Especially, the present sensor including two NH-pyrazolyl groups showed an extremely high sensitivity with low limit of detection of 7.26 and 3.67 nM. The proposed design strategy provides a wide scope for the construction of unique turn-on sensors with substantial potential in the sense of heavy metal pollution in enviromental water samples.

Supramolecular Hydrogen Bonding Assembly from Non-Coplanar Aromatic Tetra-1H-Pyrazoles with Crystallization-Induced Emission (CIE).

Here, we report a design strategy for constructing supramolecular organic frameworks by introducing 1H-pyrazole groups to aromatic cores as non-coplanar molecules to form diverse supramolecular assemblies through multiple 1H-pyrazole [N-H···N] hydrogen bonds as well as other weak interactions. The new supramolecular organic frameworks displayed interesting crystallization-induced emission (CIE) behavior.

Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression.

Enhancing neurogenesis within the hippocampal dentate gyrus (DG) is critical for maintaining brain development and function in many neurological diseases. However, the neural mechanisms underlying neurogenesis in depression remain unclear. Here, we show that microglia transfer a microglia-enriched microRNA, miR-146a-5p, via secreting exosomes to inhibit neurogenesis in depression. Overexpression of miR-146a-5p in hippocampal DG suppresses neurogenesis and spontaneous discharge of excitatory neurons by directly targeting Krüppel-like factor 4 (KLF4). Downregulation of miR-146a-5p expression ameliorates adult neurogenesis deficits in DG regions and depression-like behaviors in rats. Intriguingly, circular RNA ANKS1B acts as a miRNA sequester for miR-146a-5p to mediate post-transcriptional regulation of KLF4 expression. Collectively, these results indicate that miR-146a-5p can function as a critical factor regulating neurogenesis under conditions of pathological processes resulting from depression and suggest that microglial exosomes generate new crosstalk channels between glial cells and neurons.

Prophylactic treatment of curcumin in a rat model of depression by attenuating hippocampal synaptic loss.

Curcumin is a polyphenol substance considered to be effective in the treatment of a number of neurodegenerative diseases. However, details regarding the exact mechanisms for the protective effects of curcumin in neuropsychiatric disorders, like depression, remain unknown. In the pathogenesis of major depressive disorder (MDD) it appears that dysregulation of oxidative stress and immune systems, particularly within the hippocampal region, may play a critical role. Here, we show that pre-treatment with curcumin (40 mg kg-1) alleviates depression-like behaviors in a LPS-induced rat model of depression, effects which were accompanied with suppression of oxidative stress and inflammation and an inhibition of neuronal apoptosis in the hippocampal CA1 region, and results from ultramicrostructure electrophysiological experiments revealed that the curcumin pre-treatment significantly prevented excessive synaptic loss and enhanced synaptic functioning in this LPS-induced rat model. In addition, curcumin attenuated the increases in levels of miR-146a-5p and decreases in the expression of p-ERK signaling that would normally occur within CA1 regions of these depressed rats. Taken together, these results demonstrated that curcumin exerts neuroprotective and antidepressant activities by suppressing oxidative stress, neural inflammation and their related effects upon synaptic dysregulation. One of the mechanisms for these beneficial effects of curcumin appears to involve the miR-146a-5p/ERK signaling pathway within the hippocampal CA1 region. These findings not only elucidated some of the mechanisms underlying the neuroprotective/antidepressant effects of curcumin, but also suggested a role of curcumin as a potential therapeutic strategy for depression.

MicroRNA-204-5p reduction in rat hippocampus contributes to stress-induced pathology via targeting RGS12 signaling pathway.

BACKGROUND: Neuroinflammation occupies a pivotal position in the pathogenesis of most nervous system diseases, including depression. However, the underlying molecular mechanisms of neuroinflammation associated with neuronal injury in depression remain largely uncharacterized. Therefore, identifying potential molecular mechanisms and therapeutic targets would serve to better understand the progression of this condition. METHODS: Chronic unpredictable stress (CUS) was used to induce depression-like behaviors in rats. RNA-sequencing was used to detect the differentially expressed microRNAs. Stereotactic injection of AAV virus to overexpress or knockdown the miR-204-5p. The oxidative markers and inflammatory related proteins were verified by immunoblotting or immunofluorescence assay. The oxidative stress enzyme and products were verified using enzyme-linked assay kit. Electron microscopy analysis was used to observe the synapse and ultrastructural pathology. Finally, electrophysiological recording was used to analyze the synaptic transmission. RESULTS: Here, we found that the expression of miR-204-5p within the hippocampal dentate gyrus (DG) region of rats was significantly down-regulated after chronic unpredicted stress (CUS), accompanied with the oxidative stress-induced neuronal damage within DG region of these rats. In contrast, overexpression of miR-204-5p within the DG region of CUS rats alleviated oxidative stress and neuroinflammation by directly targeting the regulator of G protein signaling 12 (RGS12), effects which were accompanied with amelioration of depressive-like behaviors in these CUS rats. In addition, down-regulation of miR-204-5p induced neuronal deterioration in DG regions and depressive-like behaviors in rats. CONCLUSION: Taken together, these results suggest that miR-204-5p plays a key role in regulating oxidative stress damage in CUS-induced pathological processes of depression. Such findings provide evidence of the involvement of miR-204-5p in mechanisms underlying oxidative stress associated with depressive phenotype.

MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies.

Depression is a neuropsychiatric disease associated with neuronal anomalies within specific brain regions. In the present study, we screened microRNA (miRNA) expression profiles in the dentate gyrus (DG) of the hippocampus and found that miR-26a-3p was markedly downregulated in a rat model of depression, whereas upregulation of miR-26a-3p within DG regions rescued the neuronal deterioration and depression-like phenotypes resulting from stress exposure, effects that appear to be mediated by the PTEN pathway. The knockdown of miR-26a-3p in DG regions of normal control rats induced depression-like behaviors, effects that were accompanied by activation of the PTEN/PI3K/Akt signaling pathway and neuronal deterioration via suppression of autophagy, impairments in synaptic plasticity, and promotion of neuronal apoptosis. In conclusion, these results suggest that miR-26a-3p deficits within the hippocampal DG mediated the neuronal anomalies contributing to the display of depression-like behaviors. This miRNA may serve as a potential therapeutic target for the treatment of depression.

Neuroprotective effects of microRNA-211-5p on chronic stress-induced neuronal apoptosis and depression-like behaviours.

Findings from recent studies have revealed that microRNAs (miRNAs) are related to numerous neurological disorders. However, whether miRNAs regulate neuronal anomalies involved in the pathogenesis of depression remain unclear. In the present study, we screened miRNA expression profiles in the CA1 hippocampus of a rat model of depression and found that a specific miRNA, microRNA-211-5p, was significantly down-regulated in depressed rats. When miR-211-5p was up-regulated in these rats, neuronal apoptosis within the CA1 area was suppressed, effects which were accompanied with an amelioration of depression-like behaviours in these rats. These neuroprotective effects of miR-211-5p in depressed rats appear to result through suppression of the Dyrk1A/ASK1/JNK signalling pathway within the CA1 area. In further support of this proposal are the findings that knock-down of miR-211-5p within the CA1 area of normal rats activated the Dyrk1A/ASK1/JNK pathway, resulting in the promotion of neuronal apoptosis and display of depression-like behaviours in these rats. Taken together, these results demonstrate that deficits in miR-211-5p contribute to neuronal apoptosis and thus depression-like behaviours in rats. Therefore, the miR-211-5p/Dyrk1A pathway may be critically involved in the pathogenesis of depression and serve as a potential therapeutic target for the treatment of depression.

Hippocampal miR-211-5p regulates neurogenesis and depression-like behaviors in the rat.

Emerging evidence has shown that microRNAs (miRNAs) contribute to the pathogenesis of depression, a potentially life-threatening and disabling mental disorder caused by the interaction of genetic and environmental factors. However, the specific miRNAs and their underlying molecular mechanisms as involved in the pathogenesis and development of depression remain largely unknown. In the present study, we screened miRNA expression profiles and found that miR-211-5p was significantly down-regulated within the dentate gyrus (DG) hippocampus in the chronic unpredictable mild stress (CUMS) induced rat model of depression. Deficits in miR-211-5p were accompanied with reductions in neurogenesis and increased apoptosis in these CUMS rats. In contrast, an up-regulation of miR-211-5p within the DG area in CUMS rats promoted neuronal neurogenesis, reduced neuronal apoptosis via suppression of the Dyrk1A/STAT3 signaling pathway and relieved depression-like behaviors in these CUMS rats. In rats subjected to a knock-down of miR-211-5p in the DG there was an increase in neuronal apoptosis and a decrease in neuronal regeneration, effects which were accompanied with an induction of depression-like behaviors. Taken together, the results of our study reveal that altered levels of miR-211-5p in the hippocampal DG area exert a significant impact on neurogenesis, apoptosis and thus depression-like behaviors in rats. These findings suggest that the miR-211-5p/Dyrk1A pathway plays an important role in the pathogenesis of depression and may serve as a potential therapeutic target for the treatment of depression.

N-Acetylcysteine Rescues Hippocampal Oxidative Stress-Induced Neuronal Injury via Suppression of p38/JNK Signaling in Depressed Rats.

Progression of neuronal deterioration within specific brain regions is considered as one of the principal bases for the development of major depressive disorders. Therefore, protects and promotes the maintaining of normal structure and function of neurons might be a potential therapeutic strategy in the treatment of depression. Here, we report that the antioxidant, N-acetylcysteine (NAC), inhibited neuronal injury through its capacity to reduce oxidative stress and exerted antidepressant effects. Specifically, we show that antioxidant enzyme activity was significantly decreased in the hippocampal CA1 region of depressive rats, while treatment with NAC (300 mg/kg, i.p.) produced neuroprotective effects against mitochondrial oxidative stress injuries and oxidative DNA damage in CA1 neurons of these rats. Moreover, NAC treatment alleviated neuronal injury resulting from neuroinflammation and apoptosis in depressed rats, effects that were associated with reductions in dendritic spine atrophy, and synapse deficits. These effects appear to involve a down-regulation of p38 mitogen-activated protein kinase (MAPK)-JNK signaling along with an up-regulation of ERK signaling within the hippocampal CA1 region. Moreover, this NAC treatment significantly ameliorated depression-like behaviors as indicated by performance in the sucrose preference and forced swim tests (FST). Taken together, these results reveal the potential involvement of oxidative stress in the generation of depression. And, the antidepressant-like effects exerted by NAC may involve reductions in this oxidative stress that can result in neuronal deterioration. Such neuroprotective effects of NAC may indicate a potential therapeutic strategy for the treatment of stress-related depression.

Protective effect of acacetin in human periodontal ligament cells via regulation of autophagy and inflammation.

Our study investigated the effects of acacetin, a natural flavonoid compound, on the survival and expression of inflammatory related cytokines in lipopolysaccharide (LPS)-stimulated human periodontal ligament (PDL) cells. Treatment with acacetin significantly promoted survival and suppressed apoptosis in LPS-stimulated PDL cells in a dose-dependent manner, as shown by CCK-8 and flow cytometry assays, respectively. Moreover, ELISA assay showed that acacetin dose-dependently attenuated LPS-induced increases of TNF-α, IL-6 and IL-1ß in PDL cells. Western blot analysis showed that administration of acacetin dose-dependently increased the ratio of LC3II/LC3I, as well as the expression of beclin-1, as compared to LPS-stimulated PDL cells. Inhibition of autophagy by rapamycin, an autophagy inhibitor, increased the production of pro-inflammatory cytokines and decreased survival, abolishing the beneficial role of acacetin in LPS-stimulated PDL cells. In addition, the expression of GSK-3ß, a regulator of autophagy, was suppressed by administration with acacetin in a dose-dependent manner. Acacetin treatment promotes survival and suppresses inflammation in LPS-stimulated PDL cells via regulating autophagy and GSK-3ß signal in PDL cells, suggesting that acacetin may be a potential novel agent for the treatment of chronic periodontitis.