Empagliflozin, a sodium-glucose cotransporter inhibitor enhancing mitochondrial action and cardioprotection in metabolic syndrome.

Metabolic syndrome (MetS) has a large clinical population nowadays, usually due to excessive energy intake and lack of exercise. During MetS, excess nutrients stress the mitochondria, resulting in relative hypoxia in tissues and organs, even when blood supply is not interrupted or reduced, making mitochondrial dysfunction a central pathogenesis of cardiovascular disease in the MetS. Sodium-glucose cotransporter 2 inhibitors were designed as a hyperglycemic drug that acts on the renal tubules to block sugar reabsorption in primary urine. Recently they have been shown to have anti-inflammatory and other protective effects on cardiomyocytes in MetS, and have also been recommended in the latest heart failure guidelines as a routine therapy. Among these inhibitors, empagliflozin shows better clinical promise due to less influence from glomerular filtration rate. This review focuses on the mitochondrial mechanisms of empagliflozin, which underlie the anti-inflammatory and recover cellular functions in MetS cardiomyocytes, including stabilizing calcium concentration, mediating metabolic reprogramming, maintaining homeostasis of mitochondrial quantity and quality, stable mitochondrial DNA copy number, and repairing damaged mitochondrial DNA.

Gut microbiota-brain bile acid axis orchestrates aging-related neuroinflammation and behavior impairment in mice.

Emerging evidence shows that disrupted gut microbiota-bile acid (BA) axis is critically involved in the development of neurodegenerative diseases. However, the alterations in spatial distribution of BAs among different brain regions that command important functions during aging and their exact roles in aging-related neurodegenerative diseases are poorly understood. Here, we analyzed the BA profiles in cerebral cortex, hippocampus, and hypothalamus of young and natural aging mice of both sexes. The results showed that aging altered brain BA profiles sex- and region- dependently, in which TßMCA was consistently elevated in aging mice of both sexes, particularly in the hippocampus and hypothalamus. Furthermore, we found that aging accumulated-TßMCA stimulated microglia inflammation in vitro and shortened the lifespan of C. elegans, as well as behavioral impairment and neuroinflammation in mice. In addition, metagenomic analysis suggested that the accumulation of brain TßMCA during aging was partially attributed to reduction in BSH-carrying bacteria. Finally, rejuvenation of gut microbiota by co-housing aged mice with young mice restored brain BA homeostasis and improved neurological dysfunctions in natural aging mice. In conclusion, our current study highlighted the potential of improving aging-related neuro-impairment by targeting gut microbiota-brain BA axis.

Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid.

Accumulating evidence indicates gut microbiota contributes to aging-related disorders. However, the exact mechanism underlying gut dysbiosis-related pathophysiological changes during aging remains largely unclear. In the current study, we first performed gut microbiota remodeling on old mice by fecal microbiota transplantation (FMT) from young mice, and then characterized the bacteria signature that was specifically altered by FMT. Our results revealed that FMT significantly improved natural aging-related systemic disorders, particularly exerted hepatoprotective effects, and improved glucose sensitivity, hepatosplenomegaly, inflammaging, antioxidative capacity and intestinal barrier. Moreover, FMT particularly increased the abundance of fecal A.muciniphila, which was almost nondetectable in old mice. Interestingly, A.muciniphila supplementation also exerted similar benefits with FMT on old mice. Notably, targeted metabolomics on short chain fatty acids (SCFAs) revealed that only acetic acid was consistently reversed by FMT. Then, acetic acid intervention exerted beneficial actions on both Caenorhabditis elegans and natural aging mice. In conclusion, our current study demonstrated that gut microbiota remodeling improved natural aging-related disorders through A.muciniphila and its derived acetic acid, suggesting that interventions with potent stimulative capacity on A. muciniphila growth and production of acetic acid was alternative and effective way to maintain healthy aging. DATA AVAILABILITY STATEMENT: The data of RNAseq and 16 S rRNA gene sequencing can be accessed in NCBI with the accession number PRJNA848996 and PRJNA849355.

Influence of phycospheric bacterioplankton disruption or removal on algae growth and survival.

Phycospheric bacteria play a crucial role in the survival of microalgae. However, the potential of using the growth regulation and community structure modulation of phycospheric bacteria to prevent the occurrence of blooms is yet to be verified. The phycospheric bacterioplankton of Cyclotella sp. can be categorized into HNA (high nucleic acid) bacteria and LNA (low nucleic acid) bacteria. 16S rRNA sequencing showed that the HNA bacteria exhibited higher α-diversity compared to the LNA bacteria, and the microbial community composition also exhibited variations. Metagenomic sequencing further indicated the distinct ecological functions between HNA and LNA bacteria. Furthermore, the study showcased the restorative capacity of the phycospheric bacterioplankton. Biomass analysis revealed that the recovery of phycospheric bacterioplankton positively influenced the microalgae growth, thus affirming the significance of phycospheric bacterioplankton to microalgae. The community structure of phycospheric bacterioplankton demonstrated a notable decrease in the abundance of restored LNA core bacteria. Additionally, the restored phycospheric bacterioplankton exhibited a more complex co-occurrence network structure, resulting in decreased resistance and sensitivity of microalgae to adverse environments. The presence of phycospheric bacterioplankton provides a protective shield for microalgae, and thus destabilizing or removing phycospheric bacterioplankton may effectively inhibit growth of microalgae.

Tea polyphenols inhibit blooms caused by eukaryotic and prokaryotic algae.

With changes in global climate, blooms are becoming more frequent and difficult to control. Therefore, the selection of algal suppressor agents with effective inhibition and environmental safety is of paramount importance. One of the main treatment strategies is to inhibit the release of harmful algal toxins. Tea polyphenols (TP) are natural products that have been widely used in medicine, the environment, and other fields due to their antibacterial and antioxidant properties. To investigate their potential application in the treatment of algal blooms, TP were applied to three different microalgae. TP exhibited strong inhibitory effects towards all three microalgae. They stimulate the accumulation of ROS in algal cells, leading to lipid peroxidation and subsequent damage to the cell membrane, resulting in the rupture and necrosis of Cyclotella sp. and Chlorella vulgaris cells. Remarkably, it was observed that lower concentrations of TP exhibited the ability to induce apoptosis in M. aeruginosa cells without causing any structural damage. This outcome is particularly significant as it reduces the potential risk of microcystin release resulting from cell rupture. Overall, blooms dominated by different algae can be treated by adjusting the concentration of TP, a new algal suppressor, indicating strong potential treatment applications.

Impacts of a bacterial algicide on metabolic pathways in Chlorella vulgaris.

Chlorella is a dominant species during harmful algal blooms (HABs) worldwide, which bring about great environmental problems and are also a serious threat to drinking water safety. Application of bacterial algicides is a promising way to control HABs. However, the identified bacterial algicides against Chlorella and the understanding of their effects on algal metabolism are very limited. Here, we isolated a novel bacterium Microbacterium paraoxydans strain M1 that has significant algicidal activities against Chlorella vulgaris (algicidal rate 64.38 %, at 120 h). Atrazine-desethyl (AD) was then identified from strain M1 as an effective bacterial algicide, with inhibition or algae-lysing concentration values (EC50) of 1.64 µg/mL and 1.38 µg/mL, at 72 h and 120 h, respectively. LAD (2 µg/mL AD) or HAD (20 µg/mL AD) causes morphology alteration and ultrastructure damage, chlorophyll a reduction, gene expression regulation (for example, psbA, 0.05 fold at 24 h, 2.97 fold at 72 h, and 0.23 fold of the control in HAD), oxidative stress, lipid oxidation (MDA, 2.09 and 3.08 fold of the control in LAD and HAD, respectively, at 120 h) and DNA damage (average percentage of tail DNA 6.23 % at 120 h in HAD, slight damage: 5∼20 %) in the algal cells. The impacts of AD on algal metabolites and metabolic pathways, as well as the algal response to the adverse effects were investigated. The results revealed that amino acids, amines, glycosides and urea decreased significantly compared to the control after 24 h exposure to AD (p < 0.05). The main up-regulated metabolic pathways implied metabonomic resistance and defense against osmotic pressure, oxidative stress, photosynthesis inhibition or partial cellular structure damage, such as phenylalanine metabolism, arginine biosynthesis. The down-regulated glycine, serine and threonine metabolism is a major lead in the algicidal mechanism according to the value of pathway impact. The down-regulated glycine, and serine are responsible for the downregulation of glyoxylate and dicarboxylate metabolism, aminoacyl-tRNA biosynthesis, glutathione metabolism, and sulfur metabolism, which strengthen the algae-lysing effect. It is the first time to highlight the pivotal role of glycine, serine and threonine metabolism in algicidal activities, which provided a new perspective for understanding the mechanism of bacterial algicides exerting on algal cells at the metabolic level.

Mitochondrial abnormalities: a hub in metabolic syndrome-related cardiac dysfunction caused by oxidative stress.

Metabolic syndrome (MetS) refers to a group of cardiovascular risk elements comprising insulin resistance, obesity, dyslipidemia, increased glucose intolerance, and increased blood pressure. Individually, all the MetS components can lead to cardiac dysfunction, while their combination generates additional risks of morbidity and mortality. Growing evidence suggests that oxidative stress, a dominant event in cellular damage and impairment, plays an indispensable role in cardiac dysfunction in MetS. Oxidative stress can not only disrupt mitochondrial activity through inducing oxidative damage to mitochondrial DNA, RNA, lipids, and proteins but can also impair cardiomyocyte contractile function via mitochondria-related oxidative modifications of proteins central to excitation-contraction coupling. Furthermore, excessive reactive oxygen species (ROS) generation can lead to the activation of several mitochondria apoptotic signaling pathways, release of cytochrome c, and eventual induction of myocardial apoptosis. This review will focus on such processes of mitochondrial abnormalities in oxidative stress induced cardiac dysfunction in MetS.

The synergistic efficacy and safety of combined low-concentration atropine and orthokeratology for slowing the progression of myopia: A meta-analysis.

PURPOSE: To explore the efficacy and safety of combined low-concentration atropine and orthokeratology (OK) for slowing the progression of myopia. METHODS: We performed a systematic search of English and Chinese databases to collect potentially eligible randomised controlled trials (RCTs), nonrandomised controlled trials (non-RCTs) and retrospective cohort studies (REs) published between the establishment of the database and 1 January 2022. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated for each outcome. RESULTS: Fifteen studies were ultimately included in the meta-analysis, which indicated that compared with OK lenses alone, the combination of low-concentration atropine with OK lenses significantly slowed axial growth (WMD = -0.12 mm; 95% CI: -0.13 to -0.11, p < 0.001) and reduced the rate of change of the spherical equivalent refraction (WMD = 0.15 D; 95% CI: 0.06 to 0.24, p < 0.001). Additionally, the combined treatment may cause a slight increase in pupil diameter (WMD = 0.62 mm; 95% CI: 0.42 to 0.81, p < 0.001). No significant difference in the amplitude of accommodation, intraocular pressure, tear film break-up time or corneal endothelial cell density was found between the OK and combination therapy groups. CONCLUSIONS: The combination therapy of low-concentration atropine and OK lenses had a greater effect in slowing myopia progression during a 6-to-12-month treatment interval and was still effective over a 24-month period. Increased pupil diameter was the major side effect of the combination therapy, with no negative impact on the amplitude of accommodation, intraocular pressure, tear film break-up time or corneal endothelial cell density.

Environment dependent microbial co-occurrences across a cyanobacterial bloom in a freshwater lake.

Microbial taxon-taxon co-occurrences may directly or indirectly reflect the potential relationships between the members within a microbial community. However, to what extent and the specificity by which these co-occurrences are influenced by environmental factors remains unclear. In this report, we evaluated how the dynamics of microbial taxon-taxon co-occurrence is associated with the changes of environmental factors in Nan Lake at Wuhan city, China with a Modified Liquid Association method. We were able to detect more than 1000 taxon-taxon co-occurrences highly correlated with one or more environmental factors across a phytoplankton bloom using 16S rRNA gene amplicon community profiles. These co-occurrences, referred to as environment dependent co-occurrences (ED_co-occurrences), delineate a unique network in which a taxon-taxon pair exhibits specific, and potentially dynamic correlations with an environmental parameter, while the individual relative abundance of each may not. Microcystis involved ED_co-occurrences are in important topological positions in the network, suggesting relationships between the bloom dominant species and other taxa could play a role in the interplay of microbial community and environment across various bloom stages. Our results may broaden our understanding of the response of a microbial community to the environment, particularly at the level of microbe-microbe associations.

Algicidal activity of a novel indigenous bacterial strain of Paracoccus homiensis against the harmful algal bloom species, Karenia mikimotoi.

Harmful algal blooms have deleterious effects on aquatic ecosystems and human health. The application of algicidal bacteria is a promising and environmentally friendly method of preventing and eradicating harmful algal blooms. In this study, a screen for algicidal agents against harmful algal blooms was used to identify an algicidal bacterial strain (strain O-4) isolated from a Karenia mikimotoi culture. Strain O-4 exhibited a strong inhibitory effect on harmful K. mikimotoi and was identified as Paracoccus homiensis via 16S rRNA gene sequence analysis. This strain killed K. mikimotoi by secreting active algicidal compounds, which were stable at temperatures of -80-121 °C but were sensitive to strongly acidic conditions (pH = 2). The algicidal properties of strain O-4 against K. mikimotoi were cell density- and time-dependent. No significant changes or negative effects were noted for two other Chlorophyta species, which highlighted the specificity of the studied algicidal substance. Finally, single-factor experiments revealed the optimum growth conditions of strain O-4 under different pH and temperature conditions. Therefore, strain O-4 has the potential to be used as a bio-agent for reducing the biomass of harmful K. mikimotoi blooms.

[Investigation of modulating effect of Qingfei Paidu Decoction on host metabolism and gut microbiome in rats].

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.

Metabolic and Gut Microbial Characterization of Obesity-Prone Mice under a High-Fat Diet.

Obesity is characterized with high heterogeneity due to genetic abnormality, energy imbalance, gut dysbiosis, or a combination of all three. Obesity-prone (OP) and -resistant (OR) phenotypes are frequently observed in rodents, even in those given a high-fat diet (HFD). However, the underlying mechanisms are largely unknown. Male C57BL/6J mice were fed with chow or a HFD for 8 weeks. OP and OR mice were defined based on body weight gain, and integrated serum metabolic and gut microbial profiling was performed by the gas chromatography-mass spectroscopy-based metabolomic sequencing and pyrosequencing of 16S rDNA of cecum contents. A total of 60 differential metabolites were identified in comparisons among Con, OP, and OR groups, in which 27 were OP-related. These differential metabolites are mainly involved in glycolysis, lipids, and amino acids metabolism and the TCA cycle. Meanwhile, OP mice had a distinct profile in gut microbiota compared to those of OR or Con mice, which showed a reduced ratio of Firmicutes to Bacteroidetes and increased Proteobacteria. Moreover, the gut microbial alteration of OP mice was correlated with the changes of the key serum metabolites. OP-enriched Parasutterella from the Proteobacteria phylum correlated to most of metabolites, suggesting that it was essential in obesity. OP mice are distinct in metabolic and gut microbial profiles, and OP-related metabolites and bacteria are of significance for understanding obesity development.

Therapeutic Effects of Coccomyxagloeobotrydiformis on the Metabolic Syndrome in Rats.

BACKGROUND/AIMS: The metabolic syndrome (MS) is a cluster of metabolic changes that carry a high risk of cardiovascular disease (CVD). A newly discovered microalga, coccomyxagloeobotrydiformis (CGD), has been reported to improve ischemic stroke and metabolism-related indicators. We observed the therapeutic effects of CGD on MS and postulated the underlying mechanism. METHODS: A diet-induced MS model in rats was used to observe the therapeutic effects of CGD on MS. Blood-glucose and lipid indices were measured using enzymatic colorimetric kits. A biologic data acquisition and analysis system (BL-420F) was used to evaluate cardiac function. Expression of mitochondrial respiratory chain (MRC) enzymes was measured by immunofluorescence staining. The proteins associated with oxidative stress, apoptosis and inflammation were detected by western blotting. RESULTS: Body weight, abdominal circumference, fasting blood glucose , blood pressure as well as serum levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol were decreased whereas serum levels of high-density lipoprotein-cholesterol was increased in CGD-treated MS rats. CGD increased left-ventricular systolic pressure, left-ventricular end-diastolic pressure, left-ventricular systolic pressure maximum rate of increase and left-ventricular diastolic pressure maximum rate of decrease in MS rats with cardiovascular complications. CGD up-regulated expression of adenosine monophosphate-activated protein kinase and peroxisome proliferator activated receptor gamma coactivator 1-alpha in the heart, adipose tissue and skeletal muscle. Expression of the MRC subunits of ATPase 6, cytochrome b and succinate dehydrogenase complex, subunit-A was increased whereas that of uncoupling protein-2 decreased in different tissues. CGD showed anti-oxidation effects by increasing expression of superoxide dismutase and decreasing that of malondialdehyde. High expression of Bcl-2 and low expression of Bax and caspase-3 supported the anti-apoptotic effect of CGD on the cardiovascular complications of MS. CONCLUSION: CGD has a therapeutic effect on MS and associated cardiovascular complications by eliciting mitochondrial protection and having anti-oxidation and anti-apoptosis effects. CGD could be used for MS treatment.

Coccomyxa Gloeobotrydiformis Polysaccharide Inhibits Lipopolysaccharide-Induced Inflammation in RAW 264.7 Macrophages.

BACKGROUND/AIMS: Inflammation plays a vital role in the etiology and pathogenesis of chronic noncommunicable diseases (NCDs), which are the leading health issues throughout the world. Our previous studies verified the satisfactory therapeutic effects of Coccomyxa gloeobotrydiformis (CGD) polysaccharide on several NCDs. In this study, we aimed to investigate the anti-inflammatory effects of CGD polysaccharide, and the corresponding molecular mechanisms, on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. METHODS: A viability assay and a lactate dehydrogenase (LDH) assay were used to measure the cytotoxic effects of CGD polysaccharide on LPS-stimulated RAW264.7 cells. To investigate the potential anti-inflammatory mechanisms of CGD polysaccharide in LPS-stimulated RAW264.7 cells, nitric oxide (NO) production was determined using a NO assay and the expression of inflammatory mediators (PGE2, iNOS and COX-2), inflammatory cytokines (TNF-α, IL-6, IL-1ß and IL-10) and inflammation-related signaling pathways (the MAPK/NF-κB, PI3K/AKT/JNK, JAK/STAT and Nrf2/HO-1pathways) were observed by western blotting. The translocation of NF-κB p65 was also observed using an immunofluorescent assay. RESULTS: CGD polysaccharide significantly inhibited LPS-induced NO production and PGE2 expression by reducing the expression of iNOS and COX-2. It also suppressed the expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1ß, and up-regulated the expression of the anti-inflammatory cytokine IL-10. Further experiments demonstrated that CGD polysaccharide could inhibit inflammatory signaling pathways (the MAPK/NF-κB, PI3K/AKT/JNK and JAK/STAT pathways). At the same time, it enhanced the anti-inflammatory pathway Nrf2/HO-1. In addition, CGD polysaccharide did not display any cytotoxic effects, even at a high concentration. CONCLUSION: Taken together, the results suggest that CGD polysaccharide significantly inhibits LPS-induced inflammation in RAW264.7 cells. This effect lies in its regulatory effects on the signaling pathways MAPK/ NF-κB, PI3K/AKT/JNK, JAK/STAT and Nrf2/HO-1.Our findings reveal that CGD polysaccharide has the potential to be used as a relatively safe and effective drug as part of the treatment of NCDs.

Gut Microbiota Modulation Attenuated the Hypolipidemic Effect of Simvastatin in High-Fat/Cholesterol-Diet Fed Mice.

The hypolipidemic effect of simvastatin varies greatly among patients. In the current study, we investigated the gut microbial-involved mechanisms underlying the different responses to simvastatin. Male C57BL/6J mice were divided into control (Con), high-fat/cholesterol diet (HFD), antibiotic (AB), simvastatin (SV) and antibiotic_simvastatin (AB_SV) groups, respectively. At the end of the experiment, serum samples were collected for lipids and metabolomic analysis, and liver tissues for histology, gene and protein expression analysis. The results showed that antibiotic treatment not only altered the composition of gut microbiota, but attenuated the hypolipidemic effect of SV. A total of 16 differential metabolites between SV and HFD groups were identified with metabolomics, while most of them showed no statistical differences between AB_SV and HFD groups, and similar changes were also observed in bile acids profile. The expressions of several genes and proteins involved in regulating bile acids synthesis were significantly reversed by SV, but not AB_SV in HFD fed mice. In summary, our current study indicated that the hypolipidemic effect of SV was correlated with the composition of the gut microbiota, and the attenuated hypolipidemic effect of SV by gut microbiota modulation was associated with a suppression of bile acids synthesis from cholesterol.

Mitochondrial Genome Encoded Proteins Expression Disorder, the Possible Mechanism of the Heart Disease in Metabolic Syndrome.

BACKGROUND/AIMS: The direct consequence of metabolic syndrome (MS) is the increased morbidity and mortality caused by the heart disease. We tried to explain why the heart is more severely damaged during MS from the point of mitochondria, the center of cellular metabolism. METHODS: 1. The classic diet induced MS rat model was used to observe the morphological changes of mitochondria by transmission electron microscope (TEM); 2. The expression of mitochondrial DNA (mt-DNA) encoded proteins was observed by immunohistochemistry and Western blot; 3. The expression of mitochondrial ribosomal proteins (MRPs) was observed by real-time PCR. RESULTS: 1. The mitochondrial volume increased but the number was normal in myocardial cells of the MS rats. But in the hepatocytes and skeletal muscle cells, the mitochondrial number decreased; 2.The mt-DNA encoded protein cytochrome b increased significantly in heart but decreased in liver and the ATPase6 increased in liver but decreased in heart of the MS rats; 3. The mRNA levels of MRPS23, MRPL27, MRPL45 and MRPL48 elevated in heart but down-regulated in liver of the MS rats. CONCLUSION: The morphologic and functional alterations of mitochondrion in MS were tissue specific. Heart displays a distinctive pattern of mitochondrial metabolic status compared with other tissues.

Dexmedetomidine preconditioning attenuates global cerebral ischemic injury following asphyxial cardiac arrest.

BACKGROUND/AIMS: To investigate the protection effect of dexmedetomidine preconditioning on global cerebral ischemic injury following asphyxial cardiac arrest (CA) in rats. METHODS: Seventy-two rats were randomly assigned into three groups, sham group (no asphyxia), control group (asphyxia only), and dexmedetomidine preconditioned group (asphyxia + dexmedetomidine). Dexmedetomidine was administered 5 minutes before an 8 min of asphyxia. Rats were resuscitated by a standardized method. Blood O(2) and CO(2) partial pressures were, pH, base excess (BE), and blood glucose concentration measured before asphyxial CA and 1 h after resuscitation. Neurological deficit score (NDS) was measured at 12, 24, 48, and 72 h after CA. Histopathologic changes in the hippocampal region were observed by H&E staining and histopathologic damage score. Ultrastructural morphology was observed by transmission electron microscopy. HIF-1 and VEGF expression were measured by immunostaining of serial sections obtained from brain tissue. RESULTS: Asphyxial CA -induced global cerebral ischemic decreased PaO(2), pH, BE and increased PaCO(2), blood glucose. Dexmedetomidine preconditioning improved neurologic outcome, which was associated with reduction in histopathologic injury measured by H&E staining, the histopathologic damage score and electron microscopy. Dexmedetomidine preconditioning also elevated HIF-1α and VEGF expression after global cerebral ischemia following asphyxial CA. CONCLUSION: Dexmedetomidine preconditioning protected against cerebral ischemic injury and was associated with upregulation of HIF-1α and VEGF expression.

PDK1 Activity Regulates Proliferation, Invasion and Growth of Hemangiomas.

BACKGROUND: Hemangiomas are common vascular endothelial cell tumors. Abnormally activated PI3K/Akt signaling pathway is one of the most important biological characteristics of Hemangioma. 3-phosphoinositide-dependent kinase 1(PDK1), an upstream protein of Akt, regulates the activity of Akt and its downstream kinases. The objective of this study is to explore the effect of PDK1 on malignant vascular tumors and their cell signaling mechanism in mice. METHODS: Mouse Hemangioendothelioma Endothelial Cells (EOMA cells) and Nu/Nu mice were used. The silencing of PDK1 was mediated by lentiviral shRNA. Western blotting, WST-1 proliferation assay, Matrigel invasion assay, and Xenograft vascular tumor model were utilized to examine the effects and mechanism of PDK1 growth, proliferation, and invasion of an Hemangioma. RESULTS: PDK1 deficiency significantly reduced the proliferation and invasion of EOMA cells in vitro, and depressed the growth of vascular tumor in vivo by decreasing the activity of Akt signaling pathway. CONCLUSION: We hypothesize that PDK1 plays a significant role in the progression and growth of vascular tumors and targeting PDK1 may thus be considered in their treatment.

Low concentration of rapamycin inhibits hemangioma endothelial cell proliferation, migration, and vascular tumor formation in mice.

BACKGROUND: Vascular endothelial cell excessive proliferation is the main biological behavior of hemangioma. Rapamycin regulates the growth of endothelial cells by inhibiting mammalian target of rapamycin (mTOR). Thus hemangioma accompanied by excessive mTOR activation should be sensitive to rapamycin. We aimed to illustrate the effect of low-concentration rapamycin on hemangioma and provide a safe and effective drug therapy. METHODS: Mouse hemangioendothelioma endothelial cells and Nu/Nu mice were used. Rapamycin was applied in a concentration from 1 nM to 20 nM. WST-1 cell proliferation and transwell migration assays were used to analyze vascular tumor proliferation and migration in vitro. Xenograft mouse models were used to test vascular tumor growth in vivo. RESULTS: Low-concentration rapamycin (1 nM) inhibited hemangioendothelioma endothelial cell proliferation and migration in vitro and vascular tumor growth in vivo. The mechanism was decreased activation of the protein kinase B/mTOR/S6 ribosomal protein (S6) signaling pathway. CONCLUSIONS: Rapamycin used in vitro was analogous to low serum concentration rapamycin (7-16 nM) and also significantly inhibited the growth of hemangioma. These results demonstrate a low-toxic drug therapy for hemangioma and encourage continued development of rapamycin and its analogs for use in vascular tumor therapy.

Metagenomics analysis reveals effects of salinity fluctuation on diversity and ecological functions of high and low nucleic acid content bacteria.

Salinity is a critical environmental factor in marine ecosystems and has complex and wide-ranging biological effects. However, the effects of changing salinity on diversity and ecological functions of high nucleic acid (HNA) and low nucleic acid (LNA) bacteria are not well understood. In this study, we used 16S rRNA sequencing and metagenomic sequencing analysis to reveal the response of HNA and LNA bacterial communities and their ecological functions to salinity, which was decreased from 26 ‰ to 16 ‰. The results showed that salinity changes had significant effects on the community composition of HNA and LNA bacteria. Among LNA bacteria, 14 classes showed a significant correlation between relative abundance and salinity. Salinity changes can lead to the transfer of some bacteria from HNA bacteria to LNA bacteria. In the network topology relationship, the complexity of the network between HNA and LNA bacterial communities gradually decreased with decreased salinity. The abundance of some carbon and nitrogen cycling genes in HNA and LNA bacteria varied with salinity. Overall, this study demonstrates the effects of salinity on diversity and ecological functions and suggests the importance of salinity in regulating HNA and LNA bacterial communities and functions.