Resolvin D1 Induces mTOR-independent and ATG5-dependent Autophagy in BV-2 Microglial Cells.

OBJECTIVE: The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation. Autophagy is a catabolic process responsible for maintaining cellular homeostasis. In recent years, autophagy has been demonstrated to play an important role in neuroinflammation. Resolvin D1 (RvD1) is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities. However, whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation. The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways. METHODS: Mouse microglial cells (BV-2) were cultured, treated with RvD1, and examined by Western blotting, confocal immunofluorescence microscopy, transmission electron microscopy, and flow cytometry. RESULTS: RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes. Importantly, RvD1 had no significant effect on the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II (CaMK II) activation. Moreover, by downregulating ATG5, the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy. CONCLUSION: The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy, highlighting its therapeutic potential against neuroinflammation.

Surviving hot summer: Roles of phenotypic plasticity of intertidal mobile species considering microhabitat environmental heterogeneity.

For species inhabiting warming and variable thermal environment, coordinated changes in heat tolerance to temperature fluctuations, which largely depend on phenotypic plasticity, are pivotal in buffering high temperatures. Determining the roles of phenotypic plasticity in wild populations and common garden experiments help us understand how organisms survive hot summer and the warming world. We thus monitored the operative temperature of the intertidal limpets Cellana toreuma in both emergent rock and tidal pool microhabitats from June to October 2021, determined the variations of upper thermal limits of short-term acclimated and long-term acclimated limpets from different microhabitats (emergent rock and tidal pool), and further calculated the relationship between the upper thermal limits and acclimation capacity. Our results indicated that living on the emergent rock, limpets encountered more extreme events in summer. For the short-term acclimated samples, limpets on the emergent rock exhibited obvious variations of sublethal thermal limit (i.e., Arrhenius Break Point of cardiac performance, ABT) during summer months, however, this variation of ABT was absent in the limpets in the tidal pool. After the laboratory long-term acclimation, the ABTs and FLTs (Flat Line Temperature of cardiac performance, as an indicator of lethal temperature) of limpets both on the rock and in the tidal pool increased significantly in October, implying the potential existence of selection during the hot summer. Our results further showed that environmental temperature was an important driver of phenotypic plasticity. This study highlighted the changes in the thermal tolerance of intertidal limpets during summer in different microhabitats.

An innovative risk index based on neutrophils and macrophages can effectively predict prognosis and immunotherapy response in patients with muscle-invasive bladder cancer.

Background: This study aimed to establish an innovative prognostic risk index based on tumor-infiltrating immune cells (TIICs) for patients with muscle-invasive bladder cancer (MIBC). Methods: We used the CIBERSORT algorithm to calculate the abundance of immune cells in MIBC samples from the The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, and stepwise regression analysis were used to identify the included immune cells. Then, we constructed the risk index based on these cells through multivariate Cox regression analysis. By the risk index formula, we obtained the risk score of each patient and divided the patients into high-risk and low-risk groups. Kaplan-Meier (K-M) curve was used for survival analysis between groups. The receiver operating characteristic (ROC) curve was used to measure the prediction accuracy of the index. We validated the performance of the index in the IMvigor210 immunotherapy cohort. In addition, we established a nomogram combining the index and clinical characteristics. Finally, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differential genes between groups. Results: The risk index we constructed consists of three variables, including M0 macrophages, M2 macrophages, and neutrophils. K-M curve showed that the risk score had good risk stratification performance. Moreover, the risk score correlates with the patient's response to chemotherapy and immunotherapy. The nomogram has good accuracy and clinical benefit. GO and KEGG enrichment analysis revealed the tumor-promoting molecular mechanism of the index. Conclusions: The risk index based on TIICs can facilitate individualized treatment of MIBC patients by predicting prognosis and immunotherapy response.

Reply to Franski, R. Comment on "Hu et al. Determination of 2-Pentanol Enantiomers via Chiral GC-MS and Its Sensory Evaluation in Baijiu. Foods 2022, 11, 2584".

The comments [...].

Thermal heterogeneity is an important factor for maintaining the genetic differentiation pattern of the pelagic barnacle Lepas anatifera in the northwest Pacific.

Macrobenthic invertebrates are ubiquitously distributed in the epipelagic zone of the open ocean. Yet, our understanding of their genetic structure patterns remains poorly understood. Investigating the genetic differentiation patterns of pelagic Lepas anatifera and clarifying the potential roles of temperature maintaining this pattern are crucial for our understanding of the distribution and biodiversity of pelagic macrobenthos. In the present study, mitochondrial cytochrome oxidase subunit I (mtDNA COI) from three South China Sea (SCS) populations and six Kuroshio Extension (KE) region populations of L. anatifera sampled from fixed buoys and genome-wide SNPs from a subset of populations (two SCS populations and four KE region populations) were sequenced and analyzed for investigating the genetic pattern of the pelagic barnacle. Water temperature was different among sampling sites; in other words, the water temperature decreased with latitude increases, and the water temperature on the surface was higher than in the subsurface. Our result showed that three lineages with clear genetic differentiation were found in different geographical locations and depths based on mtDNA COI, all SNPs, neutral SNPs, and outlier SNPs. Lineage 1 and lineage 2 were dominant in the subsurface populations and surface populations from the KE region, respectively. Lineage 3 was dominant in the SCS populations. Historical events during the Pliocene epoch shaped the differentiation of the three lineages, while, nowadays, temperature heterogeneity maintains the current genetic pattern of L. anatifera in the northwest Pacific. The subsurface populations were genetically isolated from the surface populations in the Kuroshio Extension (KE) region, implying small-scale vertical thermal heterogeneity was also an important factor maintaining the genetic differentiation pattern of the pelagic species.

Microhabitat-specific diurnal metabolomic responses of the intertidal limpet Cellana toreuma to winter low temperature.

High-throughput determination of circadian rhythms in metabolic response and their divergent patterns in various microhabitats are crucial for understanding how organisms respond to environmental stresses. A mid-intertidal limpet Cellana toreuma was collected at various time points across both daytime and nighttime in winter during low tide for investigating the diurnal metabolomic responses to cold stress and elucidating the divergent metabolic responses to temperature variations across microhabitats. Temperatures of emergent rock microhabitats were lower than the tidal pool and even aggravated at night. A series of metabolomic responses exhibited coordinated diurnal changes in winter. Metabolic responses which were associated with cellular stress responses and energy metabolism of emergent rock microhabitat individuals were highly induced compared to the tidal pool ones. This study shed light on the diurnal patterns of metabolomic responses of intertidal molluscs in the field and emphasized the variations in metabolic responses between microhabitats.

The pleiotropic mode and molecular mechanism of macrophages in promoting tumor progression and metastasis

Macrophages are the most abundant immune cells in primary and metastatic tumor tissues. Studies have shown that macrophages mainly exhibit a tumor-promoting phenotype and play a key role in tumor progression and metastasis. Therefore, many macrophage-targeted drugs have entered clinical trials. However, compared to preclinical studies, some clinical trial results showed that macrophage-targeted therapy did not achieve the desired effect. This may be because most of what we know about macrophages comes from in vitro experiments and animal models, while macrophages in the more complex human microenvironment are still poorly understood. With the development of technologies such as single-cell RNA sequencing, we have gained a new understanding of the origin, classification and functional mechanism of tumor-associated macrophages. Therefore, this study reviewed the recent progress of macrophages in promoting tumor progression and metastasis, aiming to provide some help for the formulation of optimal strategies for macrophage-targeted therapy (AU)

The pleiotropic mode and molecular mechanism of macrophages in promoting tumor progression and metastasis.

Macrophages are the most abundant immune cells in primary and metastatic tumor tissues. Studies have shown that macrophages mainly exhibit a tumor-promoting phenotype and play a key role in tumor progression and metastasis. Therefore, many macrophage-targeted drugs have entered clinical trials. However, compared to preclinical studies, some clinical trial results showed that macrophage-targeted therapy did not achieve the desired effect. This may be because most of what we know about macrophages comes from in vitro experiments and animal models, while macrophages in the more complex human microenvironment are still poorly understood. With the development of technologies such as single-cell RNA sequencing, we have gained a new understanding of the origin, classification and functional mechanism of tumor-associated macrophages. Therefore, this study reviewed the recent progress of macrophages in promoting tumor progression and metastasis, aiming to provide some help for the formulation of optimal strategies for macrophage-targeted therapy.

Multiple genetic sources facilitate the northward range expansion of an intertidal oyster along China's coast.

Coastal artificial structures on the former mudflats provide available habitats for the rocky intertidal species which can establish new populations in these emerging habitats over their former distribution range limits. As a former southern species, the oyster Crassostrea sikamea has become a pioneer and rapidly invaded the artificial shorelines in northern China. We used a seascape genomics approach to investigate the population structure and genetic sources of C. sikamea on the coastal artificial structures, which is crucial for understanding the genetic mechanisms driving species distribution range expansion and invasion pathway of intertidal species. Five C. sikamea populations, including two artificial substrate populations (WGZ and ZAP), one oyster reef population (LS), and two natural rocky shore populations (ZS and XM), were measured using single nucleotide polymorphism (SNPs) obtained from double digest restriction-site associated DNA sequencing (ddRAD-Seq). Redundancy analyses (RDA) were implemented for investigating the relationship between local temperature variables and the temperature adaptability of C. sikamea. Genetic diversity, direction and strength of gene flow, and population structure all revealed that the LS and ZS populations were the genetic sources for the oyster populations on the emerging northern coastal artificial structures. Results of RDA showed that there were different adaptive potentials for northern and southern populations to local temperature variables and the oyster reef population which frequently suffers from heat stress owned high heat adaptability. The ZS population as a genetic source nearby the Yangtze River estuary provided mass larvae for the northern populations, and the other genetic source, the heat-tolerant LS population, in the oyster reef played an important role in the post-settlement success by providing preadapted genotypes. These results highlight the importance of multiple sources with divergent adaptative capabilities for biological invasion, and also emphasize the importance of the oyster reef in coastal biodiversity and conservation.

Determination of 2-Pentanol Enantiomers via Chiral GC-MS and Its Sensory Evaluation in Baijiu.

The enantiomeric contents of 2-pentanol of Baijiu were analyzed by liquid-liquid extraction (LLE) coupled with gas chromatography-mass spectrometry (GC-MS) using ß-cyclodextrin as a chiral stationary phase. In this study, the average enantiomeric ratios R:S were 72:28, 64:36, and 94:6 in soy sauce aroma-type Baijiu (SSB), strong aroma-type Baijiu (STB), and light aroma-type Baijiu (LTB), respectively, and only (R)- configuration was found in rice aroma-type Baijiu (RTB). The highest enantiomeric concentration of 2-pentanol was found in STB. (R)-2-pentanol dominated in 48 Baijiu studied, and the concentration of (R)-2-pentanol was higher than that of the (S)-configuration. The results showed that the enantiomers of 2-pentanol were discrepant in different aroma types of Baijiu, and it may be the result of differences in raw materials, environment, and production processes. The 2-pentanol enantiomers had different odor characteristics, with different olfactory thresholds in pure water and 46% ethanol solutions by sensory analysis. (R)-2-pentanol was described as paint, rubber, grease, while the (S)-form had mint, plastic, and pungent notes. The olfactory thresholds of (R)- and (S)-form were 163.30 mg/L and 78.58 mg/L in 46% ethanol and 12.62 mg/L and 3.03 mg/L in pure water, respectively. The different enantiomeric distribution and aroma characteristics of the 2-pentanol enantiomers in Baijiu could be a potential marker for determining adulteration.

Two complete mitochondrial genomes of the barnacle Lepas anatifera Linnaeus, 1758 (Scalpellomorpha, Lepadidae) implying the possibility of cryptic speciation.

The barnacle Lepas anatifera Linnaeus, 1758 (Scalpellomorpha, Lepadidae) is a worldwide distributed species. For investigating its genetic diversity in the northwest Pacific, two complete mitochondrial genomes were determined and analyzed. The lengths of the two complete mitogenomes were 15,708 bp and 15,703 bp, respectively. Both of them contained typical 37 genes with an identical order to L. anserifera Linnaeus, 1767 and L. australis Darwin, 1851 mitogenome. Except for ND1 and ND2, 11 protein-coding genes (PCGs) started with an ATN initiation codon (ATA, ATG, ATC, and ATT). Twelve PCGs were terminated with TAA or TAG stop codon, whereas ND1 possessed an incomplete termination codon (T-). Phylogenetic analysis revealed that L. australis and L. anserifera clustered together, and then with L. anatifera. The distinct genetic distances (0.17) based on concatenated sequence of 13 PCGs between the two mitogenomes of L. anatifera suggest the existence of cryptic speciation. Additional samples from multiple localities should be collected and analyzed to deepen the understanding of cryptic diversity within the northwest Pacific.

Modulation of Spike Count Correlations Between Macaque Primary Visual Cortex Neurons by Difficulty of Attentional Task.

Studies have shown that spatial attention remarkably affects the trial-to-trial response variability shared between neurons. Difficulty in the attentional task adjusts how much concentration we maintain on what is currently important and what is filtered as irrelevant sensory information. However, how task difficulty mediates the interactions between neurons with separated receptive fields (RFs) that are attended to or attended away is still not clear. We examined spike count correlations between single-unit activities recorded simultaneously in the primary visual cortex (V1) while monkeys performed a spatial attention task with two levels of difficulty. Moreover, the RFs of the two neurons recorded were non-overlapping to allow us to study fluctuations in the correlated responses between competing visual inputs when the focus of attention was allocated to the RF of one neuron. While increasing difficulty in the spatial attention task, spike count correlations were either decreased to become negative between neuronal pairs, implying competition among them, with one neuron (or none) exhibiting attentional enhancement of firing rate, or increased to become positive, suggesting inter-neuronal cooperation, with one of the pair showing attentional suppression of spiking responses. Besides, the modulation of spike count correlations by task difficulty was independent of the attended locations. These findings provide evidence that task difficulty affects the functional interactions between different neuronal pools in V1 when selective attention resolves the spatial competition.

Reconstruction of the evolutionary biogeography reveal the origins and diversification of oysters (Bivalvia: Ostreidae).

Oysters (Bivalvia: Ostreidae Rafinesque, 1815) live in the intertidal and shallow subtidal areas worldwide. Despite their long evolutionary histories, abundant fossil records, global distribution, and ecological significance, a systematic time-dependent biogeographical analysis of this family is still lacking. Using combined mitochondrial (COI and 16S rRNA) and nuclear (18S rRNA, 28S rRNA, H3 and ITS2) gene makers for 80% (70/88) of the recognized extant Ostreidae, we reconstructed the global phylogenetic and biogeographical relationships throughout the evolutionary history of oysters. The result provided a holistic view of the origin, migration and dispersal patterns of Ostreidae. The phylogenetic results and fossil evidence indicated that Ostreidae originated from the circum-Arctic region in the Early Jurassic. The widening of the Atlantic Ocean and changes in the Tethys Ocean further facilitated their subsequent diversification during the Cretaceous and the Palaeogene periods. In particular, Crassostrea and Saccostrea exhibited relatively low dispersal abilities and their major diversifications were consistent with the tectonic events. Environmental adaptations and reproductive patterns, therefore, should play key roles in the formation of oyster distribution patterners, rather than the dispersal ability of their planktonic larvae. The diversity dynamics inferred by standard phylogenetic are consistent with the fossil record, however, further systematic classification, especially for fossil genus Ostrea, would enhance our understanding on extant and fossil oysters. The present study of the historical biogeography of oysters provides new insights into the evolution and speciation of oysters. Our findings also provide a foundation for the assessment of evolutionary patterns and ecological processes in intertidal and inshore life.

Resolvin D1 attenuates mechanical stretch-induced pulmonary fibrosis via epithelial-mesenchymal transition.

Mechanical ventilation-induced pulmonary fibrosis plays an important role in the high mortality rate of acute respiratory distress syndrome (ARDS). Resolvin D1 (RvD1) displays potent proresolving activities. Epithelial-mesenchymal transition (EMT) has been proved to be an important pathological feature of lung fibrosis. This study aimed to investigate whether RvD1 can attenuate mechanical ventilation-induced lung fibrosis. Human lung epithelial (BEAS-2B) cells were pretreated with RvD1 for 30 min and exposed to acid for 10 min before being subjected to mechanical stretch for 48 h. C57BL/6 mice were subjected to intratracheal acid aspiration followed by mechanical ventilation 24 h later (peak inspiratory pressure 22 cmH2O, positive end-expiratory pressure 2 cmH2O, and respiratory rate 120 breaths/min for 2 h). RvD1 was injected into mice for 5 consecutive days after mechanical ventilation. Treatment with RvD1 significantly inhibited mechanical stretch-induced mesenchymal markers (vimentin and α-smooth muscle actin) and stimulated epithelial markers (E-cadherin). Tert-butyloxycarbonyl 2 (BOC-2), a lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2) antagonist, is known to inhibit ALX/FPR2 function. BOC-2 could reverse the beneficial effects of RvD1. The antifibrotic effect of RvD1 was associated with the suppression of Smad2/3 phosphorylation. This study demonstrated that mechanical stretch could induce EMT and pulmonary fibrosis and that treatment with RvD1 could attenuate mechanical ventilation-induced lung fibrosis, thus highlighting RvD1 as an effective therapeutic agent against pulmonary fibrosis associated with mechanical ventilation.

Maresin 1 attenuates the inflammatory response and mitochondrial damage in mice with cerebral ischemia/reperfusion in a SIRT1-dependent manner.

Maresin 1 (MaR1) confers brain-protective effects against cerebral ischemia/reperfusion (I/R) injury. Activation of silent information regulator 1 (SIRT1) signaling has also been demonstrated to inhibit cerebral I/R injury. We hypothesize that MaR1 may protect against cerebral I/R injury by activating SIRT1 signaling. The present study investigated the protective effect of MaR1 treatment on cerebral I/R injury and elucidated the potential mechanisms. Mice were exposed to the treatment in the presence or absence of MaR1 or the SIRT1 inhibitor EX527 and then subjected to the middle cerebral artery occlusion (MCAO) operation. MaR1 conferred a brain-protective effect by up-regulating SIRT1 and Bcl2 expression, down-regulating acetylated neuclear factor kappaB (AC-NF-κB) and Bax expression, reducing pro-inflammatory factor levels (IL-1, IL-6 and TNF-α), increasing the mitochondrial membrane potential, and diminishing neuronal degeneration, the infarct size and the neurological defects of cerebral I/R. These protective effects were partially blocked by the SIRT1 inhibitor EX527, indicating that SIRT1 signaling might be specifically involved in the protection provided by MaR1 against cerebral I/R injury. In summary, our results demonstrate that MaR1 treatment attenuates cerebral I/R injury by reducing inflammatory responses and mitochondrial damage via activation of SIRT1 signaling.

The complete mitochondrial genome of a marine mussel, Modiolus comptus (Mollusca: Mytilidae), and its phylogenetic implication.

In this study, the complete mitochondrial genome of Modiolus comptus was determined and annotated for the first time. The 15,591 bp circular genome has a base composition of 24.3% A, 38.6% T, 12.5% C, and 24.5% G, demonstrating a bias of higher AT content (63.0%) than GC content (27.0%). The mitochondrial genome contains 12 protein-coding genes (PCGs), 20 transfer RNA genes (tRNA), 2 ribosomal RNA genes (12S rRNA and 16S rRNA), and one control region. All genes of M. comptus were encoded on the heavy strand, except trnT(ugu) gene. The whole mitochondrial genome of M. comptus and 21 mitogenomes of other Mytilidae species were used for phylogenetic analysis. The result indicated the newly sequenced species had the closest relationship with Modiolus nipponicus (MK721547) and was clustered within the clade of genus Modiolus.

Death-associated protein kinase 1 mediates interleukin-1ß production through regulating inlfammasome activation in Bv2 microglial cells and mice.

Interleukin-1ß (IL-1ß) plays a crucial role in mediating inflammation and innate immunity response in the central nervous system. Death-associated protein kinase 1 (DAPK1) was shown to be involved in several cellular processes. Here, we investigated the effects of DAPK1 on IL-1ß production in microglial cells. We used a combination of in vitro (Bv2 microglial cell cultures) and in vivo (mice injected with amyloid-ß (Aß)) techniques to address the role of caspase-1 activation in release of IL-1ß. DAPK1 involvement was postulated through genetic approaches and pharmacological blockade of this enzyme. We found that Aß25-35 stimulation induced IL-1ß production and caspase-1 activation in LPS-primed Bv2 cells and mice. DAPK1 knockdown and catalytic activity inhibition reduced IL-1ß maturation and caspase-1 activation, nevertheless, DAPK1 overexpression attenuated these effects. Aß25-35-induced lysosomal cathepsin B leakage was required for DAPK1 activation. Furthermore, repeated DAPK1 inhibitor treatment ameliorated the memory impairment in Aß25-35-injected mice. Taken together, our findings suggest that DAPK1 facilitates Aß25-35-induced IL-1ß production through regulating caspase-1 activation in microglial cells.

DAPK1-ERK signal mediates oxygen glucose deprivation reperfusion induced apoptosis in mouse N2a cells.

AIMS: Death-associated protein kinase 1 (DAPK1) is a kinase found to promote neuronal apoptosis induced by ischemia. Extracellular signal-regulated kinase (ERK) was identified as a key molecule in DAPK1 signaling. However, the mechanisms of neuronal ischemia reperfusion injury remain unknown. Here, we investigate the influence of DAPK1-ERK signal on neuronal apoptosis following ischemia reperfusion. METHODS: Mouse N2a cells were used in this study and primary cultured neurons along with mice were adopted as supplements. Oxygen glucose deprivation (OGD) or administration of N-methyl-d-aspartate (NMDA) and glycine was performed on cells while middle cerebral artery occlusion (MCAO) model on mice. DAPK1 knocking down was achieved by lentiviral-delivered shRNA. Protein expressions were evaluated by western blots. Protein-protein binding was confirmed by co-immunoprecipitation and immunofluorescent assay. Apoptosis of cells was measured by flow cytometry and lacate dehydrogenase (LDH) leakage assay. RESULTS: Ischemia reperfusion resulted in increased DAPK1 and ERK activation as well as aggravated apoptosis in a time-dependent manner. DAPK1 was proved to bind to ERK during reperfusion following OGD, MCAO and excitotoxicity model. Interception of this binding by knocking down DAPK1 led to nuclear translocation of ERK and reduced apoptosis. CONCLUSION: Our study revealed the DAPK1-ERK signal as a potential mechanism contributing to neuronal apoptosis in response to ischemia reperfusion. Disruption of this signal pathway could be a promising therapeutic target against stroke.

Protectin DX Exhibits Protective Effects in Mouse Model of Lipopolysaccharide-Induced Acute Lung Injury.

BACKGROUND: Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis. Protectin DX (PDX), a pro-resolving lipid mediator, exhibits protective effects in ALI. Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide (LPS). METHODS: BALB/c mice were randomly divided into five groups: sham, LPS, LPS plus 1 ng of PDX (LPS + PDX-1 ng), LPS plus 10 ng of PDX (LPS + PDX-10 ng), and LPS plus 100 ng of PDX (LPS + PDX-100 ng). Bronchoalveolar lavage fluids (BALFs) were collected after 24 h, and total cells, polymorphonuclear leukocytes, monocyte-macrophages, and lymphocytes in BALF were enumerated. The concentration of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein (MIP)-1α, and MIP-2 in BALF was determined, and histopathological changes of the lung were observed. The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema. After determining the optimal dose of PDX, neutrophil-platelet interactions in whole blood were evaluated by flow cytometry. RESULTS: The highest dose of PDX (100 ng/mouse) failed to provide pulmonary protective effects, whereas lower doses of PDX (1 ng/mouse and 10 ng/mouse), especially 1 ng PDX, alleviated pulmonary histopathological changes, mitigated LPS-induced ALI and pulmonary edema, inhibited neutrophil infiltration, and reduced pro-inflammatory mediator (IL-1ß, IL-6, TNF-α, and MIP-1α) levels. Meanwhile, 1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-10 levels. The flow cytometry results showed that PDX could inhibit neutrophil-platelet interactions in ALI. CONCLUSION: PDX exerts protective effects in LPS-induced ALI by mitigating pulmonary inflammation and abrogating neutrophil-platelet interactions.

The pro-resolving lipid mediator Maresin 1 protects against cerebral ischemia/reperfusion injury by attenuating the pro-inflammatory response.

Inflammation plays a crucial role in acute ischemic stroke pathogenesis. Macrophage-derived Maresin 1 (MaR1) is a newly uncovered mediator with potent anti-inflammatory abilities. Here, we investigated the effect of MaR1 on acute inflammation and neuroprotection in a mouse brain ischemia reperfusion (I/R) model. Male C57 mice were subjected to 1-h middle cerebral artery occlusion (MCAO) and reperfusion. By the methods of 2,3,5-triphenyltetrazolium chloride, haematoxylin and eosin or Fluoro-Jade B staining, neurological deficits scoring, ELISA detection, immunofluorescence assay and western blot analysis, we found that intracerebroventricular injection of MaR1 significantly reduced the infarct volume and neurological defects, essentially protected the brain tissue and neurons from injury, alleviated pro-inflammatory reactions and NF-κB p65 activation and nuclear translocation. Taken together, our results suggest that MaR1 significantly protects against I/R injury probably by inhibiting pro-inflammatory reactions.