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Abstract Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major pathomechanism linking chronic stress to MDD. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of MAPK signaling pathways involved in cellular stress responses, survival, and neuroinflammation. We examined the possible contributions of MKP-1 to stress-induced MDD by comparing depression-like behaviors (anhedonia, motor retardation, behavioral despair), neuroinflammatory marker expression, and MAPK signaling pathways among rats exposed to chronic unpredictable mild stress (CUMS), overexpressing MKP-1 in the hippocampus, and CUMS-exposed rats underexpressing MKP-1 in the hippocampus. Rats exposed to CUMS exhibited MKP-1 overexpression, greater numbers of activated microglia, and enhanced expressions of neuroinflammatory markers (interleukin [IL]-6, [IL]-1β, tumor necrosis factor [TNF]-ɑ, and decreased phosphorylation levels of ERK and p38 in the hippocampus as well as anhedonia in the sucrose preference test, motor retardation in the open field, and greater immobility (despair) in the forced swimming tests. These signs of neuroinflammation and depression-like behaviors and phosphorylation levels of ERK and p38 were also observed in rats overexpressing MKP-1 without CUMS exposure, while CUMS-induced neuroinflammation, microglial activation, phosphorylation levels of ERK and p38, and depression-like behaviors were significantly reversed by MKP-1 knockdown. Moreover, MKP-1 knockdown promoted the activation of the MAPK isoform ERK, implying that the antidepressant-like effects of MKP-1 knockdown may be mediated by the ERK pathway disinhibition. These findings suggested that hippocampal MKP-1 is an essential regulator of stress-induced neuroinflammation and a promising target for antidepressant development.

IntroductionMacrophages or T-lymphocytes triggered inflammation and, consequently, activated glial cells may contribute to neuroinflammation and neurotransmitter dysfunction in schizophrenia (SZ), while omega(n)-3 polyunsaturated fatty acids (PUFAs) can attenuate some SZ symptoms through anti-inflammatory effects. However, the correlations between macrophage/T-lymphocyte-produced cytokines and glia phenotypes, between inflammatory status and PUFAs composition, between cytokines and neurotransmitter function, and between n-3 PUFAs and neurotransmitter abnormality in SZ are unclear.MethodsChanges in T-helper (h) patterns, peripheral macrophage/glial markers, PUFAs profile, membrane fluidity, and neurotransmitter functions were evaluated in SZ patients (n = 50) and healthy controls (n = 30) using ELISA, gas chromatography, fluorescence anisotropy techniques, and HPLC, respectively.ResultsCompared to the control, blood lymphocyte proliferation, the concentration of macrophage/microglia phenotype M1 markers, including cytokines IL-1β, TNF-α (Th1) and IL-6 (Th2), and astrocyte phenotype A1 marker S100β was significantly increased, while IL-17 and n-3 PUFAs contents, n-3/n-6 ratio, and membrane fluidity (FLU) were significantly decreased in SZ. Moreover, increased DA and HVA, decreased 5-HT and NE, and their metabolites appeared in SZ. Moreover, negative correlations between IL-6 and A2 marker Brain-Derived Neurotrophic Factor (BDNF) or n-3 PUFAs EPA and between IL-1β and FLU or 5HIAA, while positive correlations between EPA and 5-HIAA and between FLU and DHA were found in SZ.DiscussionThese findings showed (1) no clear Th pattern, but pro-inflammatory-dominant immunity occurred; (2) the pro-inflammatory pattern may result in the activated microglia M1 and astrocyte A1 phenotype; and (3) increased pro-inflammatory cytokines were related to decreased n-3 PUFA and decreased membrane fluidity and dysfunctional neurotransmitter systems in SZ.

A higher prevalence of depression occurs in patients with lung cancer, while poor prognosis of lung cancer is often associated with depression. Excessive inflammatory response is one of the factors in the presumptive etiology of depression, and the inflammatory microenvironment also plays a key role in tumor genesis, which may indicate a common factor between the lung and the brain. Recently, a new hypothesis, called lung-brain axis, has been proposed because critical pulmonary disorders, such as acute lung injury and acute respiratory distress syndrome appear to be responsible for mood disorder and poor cognitive outcomes. Thus, lung cancer and depression might influence each other through the lung-brain axis. Findings throughout the literature suggest that activation of the interleukin (IL)-6 pathway can activate glial M1 and A1 phenotype activity, which triggers the activity of indoleamine 2,3-dioxygenase (IDO), thereby depleting tryptophan and reducing 5-hydroxytryptamine (5-HT) synthesis. The activation of IL-6 can also inhibit the expression of the 5-HT transporter through the IL-6-JAK/STAT signaling pathway. These changes are major neuropathological aspects of depression. The pathway, as mentioned above, can also promote lung cancer since increased IDO inhibits T lymphocyte proliferation and induces lymphocyte apoptosis. Therefore, the up-regulation of IDO caused by IL-6 may be the common cause for both the development of depression and lung cancer. The purpose of this review is to analyze the inflammatory mechanism and the role of the lung-brain axis in these two disease entities. The review aims to confirm the hypothesis of the lung-brain axis and promote our understanding of the interaction between the lung and the brain.

Ageing-related structural and functional changes are accompanied by polarized imbalance of microglia and astroglia, which enhance neuroinflammation and neurodegeneration. As indispensable components of brain membranes, omega (n)-3 polyunsaturated fatty acids (PUFAs) are parallelly reduced in ageing. However, conflict results have been reported after mixed n-3 PUFA treatments. Thus, this study explored the role of glial phenotypes in ageing-induced memory impairment and compared therapeutic effects of DHA and EPA. Cognitive and spontaneous behaviors were tested in Morris Water Maze (MWM) and “open field”. Then n-3 PUFA profile, glial phenotype markers, and synaptic protein PSD-95 were detected. The results revealed that ageing rats showed memory impairment in MWM, which was improved by both PUFAs, while more effective for DHA than EPA. The imbalance between microglial M1/M2 polarizations, such as up-regulating IBA1, and down-regulating CD206 and ARG-1 were reversed by both n-3 PUFA, while DHA effect on CD206 was better. Similarly, the activation of astrocyte A1 polarization presented increasing S100B and C3, but decreasing S100a10 in ageing rat, which were attenuated by both PUFAs, while DHA was better restored the A2 S100a10 than EPA. Consistently with M1 and A1 activation in ageing rats, the concentration of proinflammatory cytokines TNF-α, interleukin (IL)-1β and IL-6 were significantly elevated accompanied by increasing TLR4 and NLRP3 inflammasome production, while DHA attenuated most cytokine changes, but EPA only suppressed IL-6. In addition, brain-derived neurotrophic factor (BDNF) was decreased in aged rats with increasing pro-BDNF, which was more powerfully down-regulated by DHA than EPA. DHA or EPA supplement increased the DHA or EPA respectively and balanced the n-6/n-3 ratio in the brain. Moreover, ageing decreased the nicotinic acetylcholine receptor (nAChR) β2 and synaptic protein PSD-95 were improved by both, but DHA was better again. In summary, enhanced microglial M1/M2 and astrocytic A1/A2 polarizations may contribute to increased proinflammatory cytokines and dysfunction of BDNF system. DHA was more effective than EPA on alleviating ageing-associated meory impairment.

Autophagy can remove endogenous inflammasome and reduce pro-inflammatory cytokine releases. While, over-expression of proinflammatory cytokines may inhibit autophagy. The mTOR is a major regulator of the autophagic process, in which PI3K/Akt pathway underlies the upstream of mTOR and modulates its activity. Both inflammatory response and mTOR-PI3K/Akt expressions were up-regulated in schizophrenia. However, the inter-relationship between chronic inflammation and autophagy, whether inflammation suppresses autophagy via PI3K/Akt/mTOR signaling pathway, and how the imbalance between two immunities causes neuroinflammation and neuropathological changes remain unknown in schizophrenia. Thus, this study determined relationship between inflammation and PI3K/Akt/mTOR pathway in schizophrenia patients (SZ), and between autophagy and glia inflammatory/neuroprotective phenotypes in a mouse model of schizophrenia.66 SZ and 44 healthy controls (CT) were enrolled. Clinical data as well as blood samples were collected. When compared to CT, peripheral autophagy factors MDC stain, and LC3 expression and autophagy activity were decreased, while the concentration of autophagy inhibitor P62, pro-inflammatory factors IL-1β, IL-6 and TNF-α concentrations were increased, and anti-inflammatory factors IL-10 and IL-4 were decreased in SZ. Blood microglia M1 marker IBA1 and astrocyte A1 S100B were up-regulated, while M2 CD206 and A2 P11 were downregulated. A negative correlation between inflammation and autophagy, and synaptic protein Beclin1 and MAP expression were found in SZ lymphocytes. In SZ lymphocytes, the PI3K/Akt/mTOR pathway was activated at both mRNA and protein levels. Then, IL-1 and IL-6 treatment significantly increased, while IL-10 decreased LC3 and Beclin 1 expression in SZ lymphocytes. Furthermore, 3-MA, an autophagy inhibitor, increased NLRP3, ASC, Caspase 1 and pro-inflammatory cytokines IL-1b and IL-6.Mouse model of schizophrenia induced by PolyI:C showed schizophrenia-like behaviors, such as increased spontaneous, impaired cognition and defected sensory-motor gating. In the brain, changes in proinflammatory cytokines, autophagy factors, glial phenotype patterns and synaptic protein were similar to peripheral changes in SZ. More important, clozapine or autophagy agonist RAPA reversed schizophrenia-like behavioral and neuropathological abnormalities, which were aborted by 3-MA.These data for the first time demonstrated imbalance between inflammation and autophagy may contribute to the neuropathology of schizophrenia.

In order to realize the visualization of unsaturated preferential flow migration of soil, a column device was designed to carry out unsaturated seepage tests. The transparent soil and digital image processing technology were used to establish the relationship between the normalized pixel intensity and the saturation of transparent soil. On this basis, the effects of the connectivity of the preferential flow path and the rotation angle of the adjacent preferential flow path on the preferential flow migration in unsaturated soils were studied by conducting laboratory model tests. The results showed that it was feasible to characterize the saturation of unsaturated transparent soils based on the intensity of image grayscale pixels. The profile of fully connection preferential flow (O-O type) and upper connection preferential flow (O-C type) presented a T-shape. The saturation of the central axis profile was obviously different from that of the central edge profile. In the lower connection preferential flow path (C-O type), the soil oil pressure and matrix potential could not make the fluid enter the preferential flow path to form the preferential flow, in which the trend of infiltration was consistent with the uniform flow. The stable infiltration rate and the wetting front moving velocity of O-C preferential flow were 1.5 times and 1.4 times of those of the C-O type, respectively. A new preferential flow was formed in the area between adjacent O-C preferential flows. The soil in that area reached higher saturation and the growth rate of saturation decreased with the increase of rotation angle. When the preferential flow rotation angle was 90°, 60° and 30°, the stable infiltration rate was respectively 1.5 times, 1.3 times and 1.2 times that of the uniform flow. As the fluid was affected by gravity, the preferential flow with a small rotation angle only infiltrated horizontally along one side of the path. However, the moving velocity of the wetting front was 1.3 times, 1.4 times, and 1.5 times that of uniform flow, respectively. The interaction between adjacent preferential flows was weakened, so it was difficult to form the new preferential flow.

Abstract Background Mounting evidences indicate that oxidative stress, neuroinflammation, and dysregulation of gut microbiota are related to neurodegenerative disorders (NDs). Butyrolactone I (BTL-I), a marine fungal metabolite, was previously reported as an in vitro neuroprotectant and inflammation inhibitor. However, little is known regarding its in vivo effects, whereas zebrafish (Danio rerio) could be used as a convenient in vivo model of toxicology and central nervous system (CNS) diseases. Methods Here, we employed in vivo and in silico methods to investigate the anti-NDs potential of BTL-I. Specifically, we established a cognitive deficit model in zebrafish by intraperitoneal (i.p.) injection of aluminum trichloride (AlCl3) (21 μg) and assessed their behaviors in the T-maze test. The proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) as well as acetylcholinesterase (AChE) activity or glutathione (GSH) levels were assayed 24 h after AlCl3 injection. The intestinal flora variation of the zebrafish was investigated by 16S rDNA high-throughput analysis. The marine fungal metabolite, butyrolactone I (BTL-I), was used to modulate zebrafish cognitive deficits evoked by AlCl3 and evaluated about its effects on the above inflammatory, cholinergic, oxidative stress, and gut floral indicators. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of BTL-I were studied by the in silico tool ADMETlab. Results BTL-I dose-dependently ameliorated AlCl3-induced cognitive deficits in zebrafish. While AlCl3 treatment elevated the levels of central and peripheral proinflammatory cytokines, increased AChE activity, and lowered GSH in the brains of zebrafish, these effects, except GSH reduction, were reversed by 25–100 mg/kg BTL-I administration. Besides, 16S rDNA high-throughput sequencing of the intestinal flora of zebrafish showed that AlCl3 decreased Gram-positive bacteria and increased proinflammatory Gram-negative bacteria, while BTL-I contributed to maintaining the predominance of beneficial Gram-positive bacteria. Moreover, the in silico analysis indicated that BTL-I exhibits acceptable drug-likeness and ADMET profiles. Conclusions The present findings suggest that BTL-I is a potential therapeutic agent for preventing CNS deficits caused by inflammation, neurotoxicity, and gut flora imbalance.

BackgroundClinical prevalence of major depression is higher in women than men, while the psychoneuroimmunological mechanisms underlying the differences between the two sexes are not fully understood.MethodsThe present study explored sex differences in the behaviors and depressive pathological mechanisms induced by chronic unpredictable mild stress (CUMS). Depression- and anxiety-like behaviors were assessed by the sucrose preference test (SPT), force swimming test (FST), open field test (OFT), and elevated plus-maze (EPM). The enzyme-linked immunosorbent assay (ELISA) was used to measure cytokine concentrations, high-performance liquid chromatography (HPLC) was used to measure monoamine neurotransmitters and metabolite contents, and real-time quantitative PCR (qPCR) and western blotting (WB) were used to measure glial parameters in the hippocampus.ResultsUnder control conditions, female rats exhibited shorter immobility times in the FST, lower interferon (IFN)-γ, and interleukin (IL)-4 levels in the hippocampus, lower norepinephrine (NE) and homovanillic acid (HVA), and higher p75 and glial-derived neurotrophic factor (GDNF) expression than male rats. CUMS markedly reduced rat body weight gain, sucrose preference, locomotor activity, number of entries into the central zone and rearing in the OFT, as well as the number of entries into and time spent in open arms of the EPM; however, CUMS increased the immobility times of the rats of both sexes in the FST. Interestingly, more pronounced changes in sucrose preference and locomotor activity were observed in female rats than in males. Consistently, CUMS-increased glucocorticoid concentration, M1 microglial marker CD11b, and peripheral IL-1β and IL-4, while decreased hippocampal IL-10, serotonin (5-HT), dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were more significant in females than in males.ConclusionThese data revealed possible mechanisms by which females suffer more depression than males at least in a stressful environment.

Neuroinflammation induced by microglial and astrocyte polarizations may contribute to neurodegeneration and cognitive impairment. Omega (n)-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory and neuroprotective effects, but conflicting results were reported after different n-3 PUFA treatments. This study examined both the change in glial polarizations in ageing rats and the differential effects of two omega-3 PUFAs. The results showed that both PUFAs improved spatial memory in ageing rats, with docosahexaenoic acid (DHA) being more effective than eicosapentaenoic acid (EPA). The imbalance between microglial M1/M2 polarizations, such as up-regulating ionized calcium binding adaptor molecule 1 (IBA1) and down-regulating CD206 and arginase-1 (ARG-1) was reversed in the hippocampus by both n-3 PUFAs, while the DHA effect on CD206 was stronger. Astrocyte A1 polarization presented increasing S100B and C3 but decreasing A2 parameter S100A10 in the ageing brain, which were restored by both PUFAs, while DHA was more effective on S100A10 than EPA. Consistent with microglial M1 activation, the concentration of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were significantly increased, which were attenuated by DHA, while EPA only suppressed IL-6. In correlation with astrocyte changes, brain-derived neurotrophic factor precursor was increased in ageing rats, which was more powerfully down-regulated by DHA than EPA. In summary, enhanced microglial M1 and astrocytic A1 polarizations may contribute to increased brain pro-inflammatory cytokines, while DHA was more powerful than EPA to alleviate ageing-associated neuroimmunological changes, thereby better-improving memory impairment.

ObjectiveDepression is positively correlated with the high incidence and low survival rate of cancers, while more cancer patients suffer depression. However, the interaction between depression and cancer, and possible underline mechanisms are unclear.MethodsChronic unpredictable mild stress (CUMS) was used to induce depression, and smoke to induce lung cancer in lung cancer vulnerable AJ mice. After 8 weeks, sucrose preference and forced swimming behaviors were tested. Blood corticosterone concentration, and levels of cytokines, lung cancer-related factors, brain-derived neurotrophic factor (BDNF) and apoptosis-related factors in the lung, amygdala and hippocampus were measured.ResultsCompared to control group, CUMS or smoke decreased sucrose consumption and increased immobility time, which were deteriorated by stress+smoke. CUMS, smoke or both combination decreased mononuclear viability and lung TNF-α concentration, increased serum corticosterone and lung interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10, IL-12 and HSP-90α concentrations. Furthermore, stress+smoke caused more increase in corticosterone and IL-10, but decreased TNF-α. In parallel, in the lung, Bcl-2/Bax and lung cancer-related factors CDK1, CDC20, P38α etc were significantly increased in stress+smoke group. Moreover, CUMS decreased BDNF, while CUMS or smoke increased TrkB and P75 concentrations, which were exacerbated by stress+smoke. In the amygdala, except for CUMS largely increased Bax/Bcl-2 and decreased TrkB, each single factor decreased BDNF and IL-10, but increased P75, IL-1β, IL-12, TNF-α concentrations. Changes in Bax/Bcl-2, IL-10 and TNF-α were further aggravated by the combination. In the hippocampus, except for CUMS largely increased P75 concentration, each single factor significantly increased Bax/Bcl-2 ratio, IL-1β and TNF-α, but decreased BDNF, TrkB and IL-10 concentrations. Changes in Bax, Bax/Bcl-2, IL-10 and TNF-α were further aggravated by the combination.ConclusionThese results suggest that a synergy between CUMS and smoke exposure could promote the development of depression and lung cancer, through CUMS increased the risk of cancer occurrence, and conversely lung cancer inducer smoke exposure deteriorated depressive symptoms.

This study aimed to explore the mechanism of fucoidan in chronic kidney disease (CKD)-triggered cognitive dysfunction. The adenine-induced ICR strain CKD mice model was applied, and RNA-Seq was performed for differential gene analysis between aged-CKD and normal mice. As a result, fucoidan (100 and 200 mg kg−1) significantly reversed adenine-induced high expression of urea, uric acid in urine, and creatinine in serum, as well as the novel object recognition memory and spatial memory deficits. RNA sequencing analysis indicated that oxidative and inflammatory signaling were involved in adenine-induced kidney injury and cognitive dysfunction; furthermore, fucoidan inhibited oxidative stress via GSK3β-Nrf2-HO-1 signaling and ameliorated inflammatory response through regulation of microglia/macrophage polarization in the kidney and hippocampus of CKD mice. Additionally, we clarified six hallmarks in the hippocampus and four in the kidney, which were correlated with CKD-triggered cognitive dysfunction. This study provides a theoretical basis for the application of fucoidan in the treatment of CKD-triggered memory deficits.

Microglia M1 phenotype causes HPA axis hyperactivity, neurotransmitter dysfunction, and production of proinflammatory mediators and oxidants, which may contribute to the etiology of depression and neurodegenerative diseases. Eicosapentaenoic acid (EPA) may counteract neuroinflammation by increasing n-3 docosapentaenoic acid (DPA). However, the cellular and molecular mechanisms of DPA, as well as whether it can exert antineuroinflammatory and neuroprotective effects, are unknown. The present study first evaluated DPA’s antineuroinflammatory effects in lipopolysaccharide (LPS)-activated BV2 microglia. The results showed that 50 μM DPA significantly decreased BV2 cell viability after 100 ng/mL LPS stimulation, which was associated with significant downregulation of microglia M1 phenotype markers and proinflammatory cytokines but upregulation of M2 markers and anti-inflammatory cytokine. Then, DPA inhibited the activation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65 pathways, which results were similar to the effects of NF-κB inhibitor, a positive control. Second, BV2 cell supernatant was cultured with differentiated SH-SY5Y neurons. The results showed that the supernatant from LPS-activated BV2 cells significantly decreased SH-SY5Y cell viability and brain-derived neurotrophic factor (BDNF), TrkB, p-AKT, and PI3K expression, which were significantly reversed by DPA pretreatment. Furthermore, DPA neuroprotection was abrogated by BDNF-SiRNA. Therefore, n-3 DPA may protect neurons from neuroinflammation-induced damage by balancing microglia M1 and M2 polarizations, inhibiting microglia-NF-κB and MAPK p38 while activating neuron-BDNF/TrkB-PI3K/AKT pathways.

Paprika was soaked in n-hexane to extract paprika pigment by using ultrasonic and microwave assisted extraction (UMAE). The effects of different operating variables were investigated and the extraction condition was optimized through orthogonal design: ultrasonic power of 50 w, microwave power of 240 w, powder-solvent ratio of 1: 25 (g/mL), microwave time of 600 s, paprika particle size of 60 mesh. At these conditions, the color value of 147 of paprika pigment was reached. Compared with the conventional water bath extraction method, UMAE has the advantages of shorter extraction time and higher efficiency, which may be related to the effect of UMAE on destroying the cellular structure of paprika.

Proinflammatory cytokine interleukin (IL)-1β can cause cognitive impairment, activate the hypothalamic-pituitary-adrenal axis and impair monoaminergic neurotransmission in the rat. IL-1β has also been shown to increase the concentration of the inflammatory mediator prostaglandin E2 (PGE2) in the blood. Omega (n)-3 fatty acids, such as eicosapentaenoic acid (EPA), which are components of fish oil, have been shown to reduce both the proinflammatory cytokines and the synthesis of PGE2. The purpose of this study was to determine whether dietary supplements of EPA would attenuate the inflammation-induced impairment of spatial memory by centrally administered IL-1β. Rats were fed with a diet of coconut oil (contained a negligible quantity of fatty acids), soybean oil (contained mainly n-6 fatty acids), or a diet of coconut oil enriched with ethyl-EPA (E-EPA). The rats were then injected intracerebroventricularly with IL-1β or saline.The results of this study demonstrated that the IL-1-induced deficit in spatial memory was correlated with an impairment of central noradrenergic and serotonergic (but not dopaminergic) function and an increase in the serum corticosterone concentration. IL-1β also caused an increase in the hippocampal PGE2 concentration. These effects of IL-1 were attenuated by the chronic administration of E-EPA. By contrast, rats fed with the soybean oil diet showed no effect on the changes induced by the IL-1 administration.

The present study demonstrated that an ω (n)-3 fatty acid, ethyl-eicosapentaenoic acid (ethyl-EPA), supplemented diet significantly attenuated the stress/anxiety behavior of rats in the “open field” and elevated plus maze, which was induced by subchronic intracerebroventricular administration of proinflammatory cytokine interleukin (IL)-1β. Ethyl-EPA also reduced the rise in serum corticosterone induced by IL-1. The n-6 fatty acid ethyl-γ-linolenic acid (ethyl-GLA) had little effect on the IL-1-induced changes in behavior and the corticosterone concentration. Following IL-1β administration, ethyl-EPA reduced the elevated prostaglandin (PG) E2 secretion and increased the secretion of antiinflammatory cytokine IL-10 from whole blood cells. Ethyl-GLA showed a similar antiinflammatory effect to ethyl-EPA. By contrast, n-6 fatty acid arachidonic acid (AA) had no effect on the behavior, immune, and endocrine changes induced by IL-1. AA alone enhanced the basal inflammatory response, raised serum corticosterone concentrations, and induced anxiety behavior in the elevated plus maze. The reduced growth rates of rats following the administration of IL-1 was attenuated by ethyl-EPA, and to a greater extent by ethyl-EPA plus ethyl-GLA, but not by AA alone or in combination with ethyl-EPA.Thus, ethyl-EPA would appear to antagonise the endocrine, immune, and behavioral effects of subchronic IL-1 administration. Ethyl-GLA only antagonised IL-1-induced inflammatory changes, whereas AA caused an increase in the secretion of corticosterone and PGE2, and induced anxiety-like behavior without enhancing the effects of IL-1.

Classic hypotheses of Alzheimer’s disease (AD) include cholinergic neuron death, acetylcholine (ACh) deficiency, metal ion dynamic equilibrium disorder, and deposition of amyloid and tau. Increased evidence suggests neuroinflammation and oxidative stress may cause AD. However, none of these factors induces AD independently, but they are all associated with the formation of Aβ and tau proteins. Current clinical treatments based on ACh deficiency can only temporarily relieve symptoms, accompanied with many side-effects. Hence, searching for natural neuroprotective agents, which can significantly improve the major symptoms and reverse disease progress, have received great attention. Currently, several bioactive marine products have shown neuroprotective activities, immunomodulatory and anti-inflammatory effects with low toxicity and mild side effects in laboratory studies. Recently, chitosan (CTS), chitooligosaccharide (COS) and their derivatives from exoskeletons of crustaceans and cell walls of fungi have shown neuroprotective and antioxidative effects, matrix metalloproteinase inhibition, anti-HIV and anti-inflammatory properties. With regards to the hypotheses of AD, the neuroprotective effect of CTS, COS, and their derivatives on AD-like changes in several models have been reported. CTS and COS exert beneficial effects on cognitive impairments via inhibiting oxidative stress and neuroinflammation. They are also a new type of non-toxic β-secretase and AChE inhibitor. As neuroprotective agents, they could reduce the cell membrane damage caused by copper ions and decrease the content of reactive oxygen species. This review will focus on their anti-neuroinflammation, antioxidants and their inhibition of β-amyloid, acetylcholinesterase and copper ions adsorption. Finally, the limitations and future work will be discussed.

Increased evidence suggests that marine unsaturated fatty acids (FAs) can protect neurons from amyloid-β (Aβ)-induced neurodegeneration. Nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC) and gas chromatography (GC) assays showed that the acetone extract 4-2A obtained from shrimp Pandalus borealis industry processing wastes contained 67.19% monounsaturated FAs and 16.84% polyunsaturated FAs. The present study evaluated the anti-oxidative and anti-inflammatory effects of 4-2A in Aβ25–35-insulted differentiated SH-SY5Y cells. Cell viability and cytotoxicity were measured by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Quantitative PCR and Western blotting were used to study the expression of neurotrophins, pro-inflammatory cytokines and apoptosis-related genes. Administration of 20 μM Aβ25–35 significantly reduced SH-SY5Y cell viability, the expression of nerve growth factor (NGF) and its tyrosine kinase TrkA receptor, as well as the level of glutathione, while increased reactive oxygen species (ROS), nitric oxide, tumor necrosis factor (TNF)-α, brain derived neurotrophic factor (BDNF) and its TrkB receptor. Aβ25–35 also increased the Bax/Bcl-2 ratio and Caspase-3 expression. Treatment with 4-2A significantly attenuated the Aβ25–35-induced changes in cell viability, ROS, GSH, NGF, TrkA, TNF-α, the Bax/Bcl-2 ratio and Caspase-3, except for nitric oxide, BDNF and TrKB. In conclusion, 4-2A effectively protected SH-SY5Y cells against Aβ-induced neuronal apoptosis/death by suppressing inflammation and oxidative stress and up-regulating NGF and TrKA expression.

A 2D imine-linked COF with a hitherto unreported htb type topology was synthesized from a linear diamine linker and a judiciously designed tetra-aldehyde building block. This work opens the door to the development of COFs with unprecedented topologies and may broaden the scope of COF functional materials by pore size and pore surface engineering.

Two stable crystalline hydrazone-linked covalent organic frameworks (COFs) (Bth-Dha and Bth-Dma) containing functional O,N,O'-chelating sites have been designed and successfully synthesized by the Schiff-base condensation reactions between benzene-1,3,5-tricarbohydrazide (Bth) and 2,5-dihydroxyterephthalaldehyde (Dha) or 2,5-dimethoxyterephthal-aldehyde (Dma), respectively. Bth-Dma exhibits strong fluorescence in the solid state and in an aqueous dispersion, while no fluorescence can be observed for Bth-Dha. Interestingly, the as-synthesized Bth-Dma can be used as a turn-off fluorescence sensor for the Fe(III) ion in aqueous solution with outstanding selectivity and sensitivity. The recognition process can be attributed to the coordination interaction between Fe(III) ion and the O,N,O'-chelating sites in the pore wall of Bth-Dma COF, as verified by X-ray photoelectron spectroscopy and 1H NMR spectroscopy. To the best of our knowledge, this is the first report on the rational design of luminescent COF with predesigned O,N,O'-chelating sites as a fluorescence sensor for highly selective and sensitive metal ion detection. This work may pave the way for designing luminescent COF sensors with functional binding sites for detecting specific metal ions.