Functional magnetic resonance imaging study on anxiety and depression disorders induced by chronic restraint stress in rats.

Persistent and negative stress stimulation is one of the most important factors leading to anxiety and depression in individuals, and it can negatively affect the normal function and structure of brain-related regions. However, the maladaptive changes of brain neural networks in anxiety and depression induced by chronic stress have not been explored in detail. In this study, we analyzed the changes in global information transfer efficiency, stress related blood oxygen level dependent (BOLD)- and diffusion tensor imaging (DTI)- signals and functional connectivity (FC) in rat models based on resting-state functional magnetic resonance imaging (rs-fMRI). The results showed that compared to control group, rats treated with chronic restraint stress (CRS) for 5 weeks had reconstructed the small-world network properties. In addition, CRS group had increased coherence and activity in bilateral Striatum (ST_R & L), but decreased coherence and activity in unilateral (left) Frontal Association Cortex (FrA_L) and unilateral (left) Medial Entorhinal Cortex (MEC_L). DTI analysis and correlation analysis confirmed the disrupted integrity of MEC_L and ST_R & L and their correlation to anxiety- and depressive-liked behaviors. Functional connectivity further showed these regions of interest (ROI) had decreased positive correlations with several brain areas, respectively. Our study comprehensively revealed the adaptive changes of brain neural networks induced by chronic stress and emphasized the abnormal activity and functional connectivity of ST_R & L and MEC_L in the pathological condition.

Dexmedetomidine Resists Intestinal Ischemia-Reperfusion Injury by Inhibiting TLR4/MyD88/NF-κB Signaling.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is a common clinical problem that occurs during various clinical pathological processes. Dexmedetomidine (DEX), a widely used anesthetic adjuvant agent, can induce protection against intestinal I/R in vivo; however, the underlying mechanism is not fully understood. In the present study, we aimed to investigate the protective effects of DEX and examine whether its mechanism was associated with the TLR4/MyD88/NF-κB signaling pathway. METHODS: Sprague-Dawley rats were pretreated with DEX and then subjected to I/R-induced intestinal injury. In vivo, intestinal histopathological examination and scoring were performed, the levels of serum intestinal fatty acid-binding protein (I-FABP), intestinal tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and expression levels of TLR4, MyD88, and NF-κB in the intestine were determined. In in vitro experiments, the human colon carcinoma cell line (Caco-2) was incubated with DEX before deprivation/reoxygenation (OGD/R) treatment. The cell viability of Caco-2 cells, the levels of lactate dehydrogenase (LDH), TNF-α, and IL-1ß in the supernatant, as well as protein expression of TLR4, MyD88, and NF-κB in Caco-2 cells, were measured. Statistical analysis was performed using SPSS version 21.0. RESULTS: DEX preconditioning significantly reduced the intestinal pathological Chiu's score, serum I-FABP, intestinal TNF-α, IL-1ß levels, and the protein expression of TLR4, MyD88, and NF-κB in the rats with intestinal I/R injury. Similarly, in vitro, DEX pretreatment protected against OGD/R-induced Caco-2 cell damage and inhibited TLR4/MyD88/NF-κB signaling, as evidenced by increased cell viability, decreased LDH activity, reduced TNF-α and IL-1ß levels, as well as downregulated TLR4, MyD88, and NF-κB protein levels. CONCLUSIONS: Our findings suggested that DEX could reduce intestinal I/R injury in rats and OGD/R damage in Caco-2 cells, and this protection might be attributed to antiinflammatory effects and inhibition of the TLR4/MyD88/NF-κB signaling pathway.

A phosphorescence "turn-on" probe for the detection and imaging of Al3+ based on aggregation-induced emission.

Aggregation-induced emission luminogens (AIEgens) have been widely used to design fluorescent probes for chemosensing and bioimaging. However, it is still challenging to design long-lived AIE-active probes due to the lack of aggregation-induced phosphorescence (AIP) luminogens. In this work, we design and synthesize a long-lived molecular probe with aggregation-induced phosphorescence property for aluminum ion-specific detection by introducing multiple carboxylic acid groups in a unique twisted molecular skeleton, and develop a first phosphorescent detection method for aluminum ion based on aggregation-induced emission mechanism. The introduction of six carboxylic acid groups into the probe not only significantly enhances the water-solubility but also provides specific recognition unit for aluminum ions via complexation. The probe shows a very sharp emission enhancement in the presence of aluminum ions via aluminum ion-triggered aggregation-induced emission. The cytotoxicity test of the probe shows its biocompatible nature, and further imaging results in live human cells and roots of live Arabidopsis thaliana demonstrates that the designed AIP-active probe is capable of monitoring aluminum ions in complex biological systems. This work proposes a general design strategy for AIP-active probes, and provides valuable use of these AIP-active probes in bioimaging.

Photophysical Switching between Aggregation-Induced Phosphorescence and Dual-State Emission by Isomeric Substitution.

It is attractive but highly challenging to achieve controllable regulation of photophysical properties of pure organic luminogens, due to distinct work mechanisms and molecular structures. Here, a strategy to regulate in a controllable way the emission behavior of luminogens is reported, according to which long-lived aggregation-induced emission (AIE) can be switched to short-lived dual-state emission (DSE) by an isomer-based substitution reaction. Three luminogens with sharply different photophysical behaviors, including aggregation-induced phosphorescence and dual-state fluorescence emission, were obtained through a substitution reaction with three isomers. Freely rotating structures are attributed to aggregation-induced phosphorescence behavior, whereas twisted rigidification of the molecule greatly contributes to its dual-state emission phenomenon. This work contributes to the controlled regulation of photophysical behaviors through simple reactions and provides a solid evidence to support the key role of the prohibition of intramolecular rotation in aggregation-induced emission process and molecular design of dual-state emitters.

Halogenated tetraphenylethene with enhanced aggregation-induced emission: an anomalous anti-heavy-atom effect and self-reversible mechanochromism.

Halogenated tetraphenylethene derivatives show a unique anti-heavy-atom effect where introducing heavy halogens like bromine greatly improves the fluorescence quantum yield upon aggregation, contrary to the classic heavy-atom effect. The unique self-reversible mechanochromism of brominated TPE is attributed to re-generation of halogen-halogen bonding after its breakage.

Rational Design of Dual-State Emission Luminogens with Solvatochromism by Combining a Partially Shared Donor-Acceptor Pattern and Twisted Structures.

We report a general design strategy for a new class of luminogens with dual-state emission (DSEgens) that are brightly emissive in both the solution and solid state, with solvatochromism properties, by constructing a partially shared donor-acceptor pattern based on a twisted molecule. The DSEgens with bright fluorescence emission in both the solid and solution state demonstrate a unique solvatochromism behaviour depending on solvent polarity and thus may have applications in anti-counterfeiting.

A water-soluble molecular probe with aggregation-induced emission for discriminative detection of Al3+ and Pb2+ and imaging in seedling root of Arabidopsis.

Luminogens with aggregation-induced emission (AIE) have been used to develop a new type of molecular probes based on analyte-triggered aggregation, but it still remains a challenge to design water-soluble AIE-active probe for specific detection of metal ions. Herein, we designed and synthesized a water-soluble molecular probe with AIE property for discriminative detection of aluminum ion and lead ion. Four carboxylic acid groups were incorporated into a tetraphenylethylene unit to enhance the coordination affinity and increase water-solubility in aqueous solution. The designed probe can be selectively lighted up by aluminum ion and lead ion via coordination-triggered AIE process. Discrimination of aluminum ion and lead ions based on the probe can be achieved in quantitative manner with the assistance of suitable masking reagents. This probe was further used to image aluminum ions in living cells of seedling roots of Arabidopsis, and the results showed that this probe is capable of imaging aluminum ions in living cells avoiding the interference of lead ions, and is suited for long-term imaging due to its excellent photostability. This work expands the application scope of AIE-active probes in discriminative detection of metal ions, and provides a design direction for water-soluble AIE probes to avoid the false signals from self-precipitation under physiological conditions.

Thiol-ene click reaction-induced fluorescence enhancement by altering the radiative rate for assaying butyrylcholinesterase activity.

Butyrylcholinesterase (BChE) generally acts as an important plasma biomarker for clinical diagnosis due to its major contribution to human plasma cholinesterase levels, but its current fluorometric assay relying on fluorogenic substrates frequently suffers from the lack of sufficiently fast response time and specific recognition of substrates relative to the traditional Ellman's method. In this work, we report a fluorescent molecular probe for assaying BChE activity based on thiol-triggered fluorescence enhancement via thiol-ene click reactions. A low-temperature experiment and theoretical analysis exclude the possibility of weak fluorescence of the probe caused by an intramolecular photoinduced electron transfer process and support the main cause of an ultraslow radiative rate due to the introduction of two acrylyl groups. This probe has sensitive fluorescence responses to thiols via thiol-ene click chemistry, and it can distinguish between glutathione and cysteine or homocysteine in different emission colors. The rapid reaction kinetics of this probe enables it to monitor hydrolysis reactions catalyzed by butyrylcholinesterase (BChE) in a real-time manner. This probe is used to develop the first fluorometric assay of BChE activity based on fluorescence enhancement triggered by thiol-ene click chemistry using butyrylthiocholine as the substrate. The established BChE assay shows excellent sensitivity, and is capable of avoiding the interference from glutathione and acetylcholinesterase (AChE) in a complex matrix. The inhibition test of tacrine on BChE with this assay substantiates its feasibility in screening potential inhibitors of BChE. This work demonstrates a design strategy of fluorescent probes lighted up by thiol-ene click reactions, reveals the main cause of thiol-triggered fluorescence enhancement by altering the radiative rate, and provides the first fluorometric assay of BChE based on rapid thiol-ene click reactions.

Inhibition of mitochondrial permeability transition pore opening contributes to cannabinoid type 1 receptor agonist ACEA-induced neuroprotection.

Cannabinoid type 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA) induces neuroprotection against brain ischemia, and the mechanism, however, is still elusive. In this study, we used bilateral common carotid artery occlusion (BCCAO) in mice and oxygen-glucose deprivation (OGD) in primary cultured neurons to mimic brain ischemic injury, and hypothesized that cannabinoid CB1 receptor agonist ACEA protects ischemic neurons via inhibiting the opening of mitochondrial permeability transition pore (MPTP). In vivo, we found that BCCAO treatment reduced the neurological functions, increased the number of apoptotic neuronal cells and deteriorated the mitochondrial morphology in the ischemic brain tissue. And in vitro, we observed that OGD injury reduced cell viability, mitochondrial function and anti-oxidant SOD2 expression, increased lactate dehydrogenase (LDH), mitochondrial cytochrome C (Cyto C) and apoptosis-inducing factor (AIF) releases, elevated the cell apoptosis and mitochondrial superoxide level. And the CB1 receptor agonist ACEA significantly abolished the BCCAO and OGD-induced neuronal injury above. However, the MPTP opener atractyloside (Atr) markedly reversed the ACEA-induced neuroprotective effects, inhibited the mitochondrial Cyto C and AIF releases and relieved the mitochondrial swelling, but the MPTP inhibitor cyclosporin A (CsA) did not cause significant effects on the ACEA-induced neuroprotection above. These findings indicated that inhibition of MPTP opening may be involved in the cannabinoid CB1 receptor agonist ACEA-induced neuroprotection.

Profiling peripheral microRNAs in obesity and type 2 diabetes mellitus.

Mechanisms of type 2 diabetes mellitus (T2DM) remain elusive, in which obesity (OB) is considered as one of the major risk factors for the disease. A microRNA (miRNA) is a small non-coding RNA molecule functioning in RNA silencing and post-transcriptional regulation of gene expression. It has been demonstrated that some miRNAs can exist in serum stably and is closely related to various diseases. The goal of our study was to identify whether the deregulation of serum miRNAs was associated with T2DM and obesity. Twenty-five subjects with T2DM2, 25 healthy controls, 25 subjects with obesity, and 25 subjects with T2DM combined with obesity were included in the study. A total of 536 miRNA serum samples from these four groups were studied by miRNA polymerase chain reaction (PCR) panels. Data showed that miR-152 and miR-17 were significantly elevated in the OB group, whereas miR-138 was significantly decreased in OB group when compared to controls, T2DM, or T2DM+obesity group. In addition, level of MiR-593 was significantly lower in T2DM group and T2DM+obesity group when compared with controls. Further analysis revealed that the four miRNAs can be used as potential biomarkers to distinguish obesity from T2DM, OB+T2DM, and healthy subjects. Our study is one of the pioneer studies showing the differences in peripheral miRNA level in obesity, T2DM and T2DM combined with obesity. The study results suggest the potential utility of miRNAs in the prediction for obesity and T2DM.