Rothia dentocariosa endocarditis with brain abscess and splenic abscess: case report and brief review.

Rothia dentocariosa is a conditionally pathogenic bacterium that may cause infective endocarditis (IE) in selected patients and give rise to a variety of clinical complications, albeit it is not a common IE pathogen. We present the case of a patient diagnosed with Rothia dentocariosa-associated IE secondary to influenza B and thrombocytopenic purpura. The blood culture revealed Rochebacterium caries, cardiac ultrasound detected vegetation, while brain and spleen abscesses manifested and progressively deteriorated. Despite a suboptimal response to anti-infective therapy, the patient ultimately underwent aortic valve replacement. Discharge from the hospital was achieved upon control of the brain abscess and spleen abscess.

Comparison of the Efficacy of Indwelling Gastric Tubes in Preoperative and Postoperative Patients With Oral and Maxillofacial Malignancies.

PURPOSE: To explore the optimal plan for the timing of indwelling gastric tube placement in oral and maxillofacial malignant tumor patients. DESIGN: A prospective randomized controlled trial. METHODS: 80 patients with oral and maxillofacial tumor were selected, and 40 patients were Pre-operative group. The remaining 40 patients were the control group, called Postoperative group. The body weight and hospital stay of the two groups were observed before and after surgery. Blood samples were taken before surgery and 1, 3 and 7 days after surgery to detect hemoglobin and plasma albumin. FINDINGS: The number of postoperative hospitalization days in the pre-operative group was significantly lower than that in the post-operative group; postoperative hemoglobin and plasma albumins were lower in both groups compared with the preoperative level. CONCLUSIONS: Preoperative nasogastric tube ensured early postoperative administration of gastrointestinal nutrition, promoted postoperative plasma albumin recovery, and shortened the days of hospitalization.

Synthesis, antioxidant and anti-hypoxia activities of 6-hydroxygenistein and its methylated derivatives. / 6-ç¾ŸåŸºæŸ“æ–™æœ¨ç´ åŠå ¶ç”²åŸºåŒ–è¡ç”Ÿç‰©çš„åˆæˆå’ŒæŠ—æ°§åŒ–ä¸ŽæŠ—ç¼ºæ°§æ´»æ€§.

OBJECTIVES: Hypoxia is a common pathological phenomenon, usually caused by insufficient oxygen supply or inability to use oxygen effectively. Hydroxylated and methoxylated flavonoids have significant anti-hypoxia activity. This study aims to explore the synthesis, antioxidant and anti-hypoxia activities of 6-hydroxygenistein (6-OHG) and its methoxylated derivatives. METHODS: The 6-OHG and its methoxylated derivatives, including 4',6,7-trimethoxy-5-hydroxyisoflavone (compound 3), 4',5,6,7-tetramethoxyisoflavone (compound 4), 4',6-imethoxy-5,7-dihydroxyisoflavone (compound 6), and 4'-methoxy-5,6,7-trihydroxyisoflavone (compound 7), were synthesized by methylation, bromination, methoxylation, and demethylation using biochanin A as raw material. The structure of these products were characterized by 1hydrogen-nuclear magnetic resonance spectroscopy (1H-NMR) and mass spectrometry (MS). The purity of these compounds was detected by high pressure chromatography (HPLC). The antioxidant activity in vitro was investigated by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) free radical scavenging assay. PC12 cells were divided into a normal group, a hypoxia model group, rutin (1×10-9-1×10-5 mol/L) groups, and target compounds (1×10-9-1×10-5 mol/L) groups under normal and hypoxic conditions. Cell viability was detected by cell counting kit-8 (CCK-8) assay, the target compounds with excellent anti-hypoxia activity and the drug concentration at the maximum anti-hypoxia activity were screened. PC12 cells were treated with the optimal concentration of the target compound or rutin with excellent anti-hypoxia activity, and the cell morphology was observed under light microscope. The apoptotic rate was determined by flow cytometry, and the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected by Western blotting. RESULTS: The structure of 6-OHG and its 4 methylated derivatives were correct, and the purity was all more than 97%. When the concentration was 4 mmol/L, the DPPH free radical removal rates of chemical compounds 7 and 6-OHG were 81.16% and 86.94%, respectively, which were higher than those of rutin, the positive control. The removal rates of chemical compounds 3, 4, and 6 were all lower than 20%. Compared with the normal group, the cell viability of the hypoxia model group was significantly decreased (P<0.01). Compared with the hypoxia model group, compounds 3, 4, and 6 had no significant effect on cell viability under hypoxic conditions. At all experimental concentrations, the cell viability of the 6-OHG group was significantly higher than that of the hypoxia model group (all P<0.05). The cell viability of compound 7 group at 1×10-7 and 1×10-6 mol/L was significantly higher than that of the hypoxia model group (both P<0.05). The anti-hypoxia activity of 6-OHG and compound 7 was excellent, and the optimal drug concentration was 1×10-6 and 1×10-7 mol/L. After PC12 cells was treated with 6-OHG (1×10-6 mol/L) and compound 7 (1×10-7 mol/L), the cell damage was reduced, the apoptotic rate was significantly decreased (P<0.01), and the protein expression levels of HIF-1α and VEGF were significantly decreased in comparison with the hypoxia model group (both P<0.01). CONCLUSIONS: The optimized synthesis route can increase the yield of 6-OHG and obtain 4 derivatives by methylation and selective demethylation. 6-OHG and compound 7 have excellent antioxidant and anti-hypoxia activities, which are related to the structure of the A-ring ortho-triphenol hydroxyl group in the molecule.

Preparation of copolymer 7-hydroxyethyl chrysin loaded PLGA nanoparticles and the in vitro release. / 7-ç¾Ÿä¹™åŸºç™½æ¨ç´ èšä¹³é ¸-ç¾ŸåŸºä¹™é ¸å ±èšç‰©çº³ç±³ç²’çš„åˆ¶å¤‡åŠä½“å¤–é‡Šæ”¾è¯„ä»·.

OBJECTIVES: To prepare 7-hydroxyethyl chrysin (7-HEC) loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles and to detect the in vitro release. METHODS: The 7-HEC/PLGA nanoparticles were prepared by emulsification solvent volatilization method. The particle size, polydispersity index (PDI), encapsulation rate, drug loading and zeta potential were measured. The prescription was optimized by single factor investigation combined with Box-Behnken response surface method. Mannitol was used as protectant to prepare lyophilized powder, and the optimal formulation was characterized and studied for the in vitro release. RESULTS: The optimal formulation of 7-HEC/PLGA nanoparticles was as follows: drug loading ratio of 2.12∶20, oil-water volume ratio of 1∶14.7, and 2.72% soybean phospholipid as emulsifier. With the optimal formulation, the average particle size of 7-HEC/PLGA nanoparticles was (240.28±0.96) nm, the PDI was 0.25±0.69, the encapsulation rate was (75.74±0.80)%, the drug loading capacity was (6.98±0.83)%, and the potentiostatic potential was (－18.17±0.17) mV. The cumulative in vitro release reached more than 50% within 48 h. CONCLUSIONS: The optimized formulation is stable and easy to operate. The prepared 7-HEC/PLGA nanoparticles have uniform particle size, high encapsulation rate and significantly higher dissolution rate than 7-HEC.

Moslosooflavone protects against brain injury induced by hypobaric hypoxic via suppressing oxidative stress, neuroinflammation, energy metabolism disorder, and apoptosis.

OBJECTIVES: To investigate the protect effect of moslosooflavone against brain injury induced by hypobaric hypoxia (HH) in mice. METHODS: Protective effects of moslosooflavone in oxidative stress, neuroinflammation, energy metabolism disorder, and apoptosis were studied in HH-induced brain damage mice. The pathological morphology in the cortex of mice was determined by hematoxylin and eosin staining. The related protein expressions were detected by western blot. KEY FINDINGS: Moslosooflavone improved HH-induced brain histopathological changes, reduced the contents of ROS and MDA, and elevated the levels of antioxidant enzymes and GSH in HH-exposed brains of mice. Moslosooflavone also markedly enhanced the ATPase activities and PK, ATP contents, while reducing LDH activity and the LD, TNF-α, IL-1ß, and IL-6 contents HH-exposed brains of mice. In addition, moslosooflavone notably decreased the expression of HIF-1α, VEGF, Bax, and cleaved caspase-3 dramatically increasing the expression of Bcl-2, Nrf2, and HO­1 in HH-exposed brains of mice. CONCLUSIONS: Our current studies indicate that moslosooflavone protects HH-induced brain injury possibly through alleviating oxidative stress and neuroinflammation, maintaining the balance of energy metabolism, and inhibiting cell apoptosis.

Nitronyl Nitroxide Ameliorates Hypobaric Hypoxia-Induced Cognitive Impairment in Mice by Suppressing the Oxidative Stress, Inflammatory Response and Apoptosis.

Abundant investigations have shown that hypobaric hypoxia (HH) causes cognitive impairment, mostly attributed to oxidative stress, inflammation, and apoptosis. HPN (4'-hydroxyl-2-subsitiuted phenylnitronyl nitroxide) is an excellent free radical scavenger with anti-inflammatory and anti-apoptotic activities. Our previous study has found that HPN exhibited neuroprotective effect on HH induced brain injury. In the present study, we examined the protective effect and potential mechanism of HPN on HH-induced cognitive impairment. Male mice were exposed to HH at 8000 m for 3 days with and without HPN treatment. Cognitive performance was assessed by the eight-arm radical maze. The histological changes were assayed by Nissle staining. The hippocampus cell apoptosis was detected by Tunnel staining. The levels of inflammatory cytokines and oxidative stress markers were detected. The expression of oxidative stress, inflammation-related and apoptosis-related proteins was determined by western blot. HPN administration significantly and mitigated HH induced histological damages and spatial memory loss with the evidence of decreased working memory error (WME), reference memory error (RME), total errors (TE) and total time (TT). In addition, HPN treatment significantly decreased the content of H2O2 and MDA, increased the levels of SOD, CAT, GSH-Px and GSH, and inhibited the synthesis of TNF-α, IL-1ß and IL-6. Moreover, HPN administration could down-regulate the expression of NF-κB, TNF-α, Bax, and cleaved caspase-3 and up-regulate the expression of Nrf2, HO-1 and Bcl-2. The number of apoptotic cells was also significantly decreased in the hippocampus of mice in the HPN group. There results indicate that HPN improve HH-induced cognitive impairment by alleviating oxidative stress damage, suppressing inflammatory response and apoptosis and may be a powerful candidate compound for alleviating memory loss induced by HH.

Simulated microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia.

Oxidative stress has been considered to be closely related to spaceflight-induced bone loss; however, mechanism is elusive and there are no effective countermeasures. Using cultured rat calvarial osteoblasts exposed to microgravity simulated by a random positioning machine, this study addressed the hypotheses that microgravity-induced shortening of primary cilia leads to oxidative stress and that primary cilium protection prevents oxidative stress and osteogenesis loss. Microgravity was found to induce oxidative stress (as represented by increased levels of reactive oxygen species (ROS) and malondialdehyde production, and decreased activities of antioxidant enzymes), which was perfectly replicated in osteoblasts growing in NG with abrogated primary cilia (created by transfection of an interfering RNA), suggesting the possibility that shortening of primary cilia leads to oxidative stress. Oxidative stress was accompanied by mitochondrial dysfunction (represented by increased mitochondrial ROS and decreased mitochondrial membrane potential) and intracellular Ca2+ overload, and the latter was found to be caused by increased activity of Ca2+ channel transient receptor potential vanilloid 4 (TRPV4), as also evidenced by TRPV4 agonist GSK1016790A-elicited Ca2+ influx. Supplementation of HC-067047, a specific antagonist of TRPV4, attenuated microgravity-induced mitochondrial dysfunction, oxidative stress, and osteogenesis loss. Although TRPV4 was found localized in primary cilia and expressed at low levels in NG, microgravity-induced shortening of primary cilia led to increased TRPV4 levels and Ca2+ influx. When primary cilia were protected by miR-129-3p overexpression or supplementation with a natural flavonoid moslosooflavone, microgravity-induced increased TRPV4 expression, mitochondrial dysfunction, oxidative stress, and osteogenesis loss were all prevented. Our data revealed a new mechanism that primary cilia function as a controller for TRPV4 expression. Microgravity-induced injury on primary cilia leads to increased expression and overactive channel of TRPV4, causing intracellular Ca2+ overload and oxidative stress, and primary cilium protection could be an effective countermeasure against microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts.

Stress measurement of aero-engine thin-walled catheter based on ultrasonic guided wave.

A pipeline system made of catheters is used for liquid-gas transportation in aero-engines. It is important to measure the residual stresses, such as the assembly stress in this system, as they influence performance and lifetime. Compared to other testing techniques, ultrasonic measurement methods based on acoustic-elastic effects can better solve problems. For the above requirements, this paper researches an aero-engine thin-wall catheter's assembly stress measurement method based on ultrasonic guided waves's acoustic, elastic effect. The propagation and dispersion characteristics of guided ultrasonic waves in the catheter were studied. Then, the excitation frequency, guided wave mode, and single-mode excitation mode of the simulation model were determined. Next, a finite element simulation model was established for simulation experiments. In order to reduce the influence of sampling rate and working environment noise on the measurement accuracy of assembly stress, the ultrasonic guided wave signal was processed by the wavelet threshold method. A good noise reduction effect was obtained by determining the wavelet base and the number of decomposition layers. Finally, an experimental platform was built to measure the assembly stress of thin-walled catheters. The maximum measurement error of the assembly stress of a thin-walled catheter was 21.1 MPa, which verified the feasibility of the measurement method. This study provides a promising method for accurately measuring the assembly stress of thin-walled catheters in aero-engines.

Research progress on the preparation and application of flavonoid nanocrystals. / é»„é ®ç±»åŒ–åˆç‰©çº³ç±³æ™¶ä½“çš„åˆ¶å¤‡åŠåº”ç”¨ç ”ç©¶è¿›å±•.

Flavonoids have been reported to possess significant pharmacological activities,such as antioxidant, anti-inflammatory and anticancer effects. However, the low solubility and low bioavailability limits their clinical application. Nanocrystal technology can solve the delivery problems of flavonoids by reducing particle size, increasing the solubility of insoluble drugs and improving their bioavailability. This article summaries nanosuspension preparation methods and the stabilizers for flavonoid nanocrystals, and reviews the drug delivery routes including oral, Injection and transdermal of flavonoid nanocrystals, to provide information for further research on nanocrystal delivery system of flavonoids.

Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity.

The molecular mechanism for the microgravity-induced decrease in bone formation remains unclear and there is a lack of effective specific preventative therapies. We recently reported that primary cilia of osteoblasts became shorter and even disappeared when the cells were exposed to random positioning machine (RPM)-simulated microgravity and that the microgravity-induced loss of osteogenic potential of osteoblasts could be attenuated when the resorption of primary cilia was prevented by treatment with 0.1 µM cytochalasin D. In the current study, it was further found that the loss of the osteogenic capacity of rat calvarial osteoblasts (ROBs) was associated with the inhibition of the BMP-2/Smad1/5/8 signalling pathway, of which most of the signalling proteins including BMP-2, BMPRII, Smad1/5/8 and p-Smad1/5/8 were found localized to primary cilia. Accompanying the resorption of primary cilia following the cells being exposed to simulated microgravity, the expression levels of these signalling proteins were reduced significantly. Furthermore, the expression of miRNA-129-3p, a microRNA previously reported to control cilium biogenesis, was found to be reduced quickly and changed in a similar tendency with the length of primary cilia. Moreover, overexpression of miRNA-129-3p in ROBs significantly attenuated microgravity-induced inhibition of BMP-2 signalling and loss of osteogenic differentiation and mineralization. These results indicated the important role of miRNA-129-3p in microgravity-induced resorption of primary cilia of osteoblasts and the potential of replenishing the miRNA-129-3p as an effective countermeasure against microgravity-induced loss of primary cilia and impairment of osteoblast function.

circ_0025033 promotes ovarian cancer development via regulating the hsa_miR-370-3p/SLC1A5 axis.

BACKGROUND: Circular RNAs (circRNAs) appear to be important modulators in ovarian cancer. We aimed to explore the role and mechanism of circ_0025033 in ovarian cancer. METHODS: qRT-PCR was conducted to determine circ_0025033, hsa_miR-370-3p, and SLC1A5 mRNA expression. Functional experiments were conducted, including Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, tube formation, xenograft tumor model assay, western blot analysis of protein levels, and analysis of glutamine metabolism using commercial kits. Their predicted interaction was confirmed using dual-luciferase reporter and RNA pull-down. RESULTS: circ_0025033 was upregulated in ovarian cancer; its knockdown induced proliferation, invasion, angiogenesis, glutamine metabolism, and apoptosis in vitro, and blocked tumor growth in vivo. circ_0025033 regulated ovarian cancer cellular behaviors via sponging hsa_miR-370-3p. In parallel, SLC1A5 might abolish the anti-ovarian cancer role of hsa_miR-370-3p. Furthermore, circ_0025033 affected SLC1A5 via regulating hsa_miR-370-3p. CONCLUSION: circ_0025033 might promote ovarian cancer progression via hsa_miR-370-3p/SLC1A5, providing an interesting insight into ovarian cancer tumorigenesis.

[The effects of different herbal compound and extracts from different extraction methods on hypoxia tolerance in mice].

Objective: To investigate the effects of different prescription compositions of traditional Chinese medicine and its different extraction methods of compound formula extracts on hypoxia tolerance in mice, in order to preferably select their prescription compositions and preparation extraction methods. Methods: Male BALB/c mice were randomly divided into 6 groups: blank control group, compound danshen group, compound Rhodiola Rosea alcohol-water extract group (Rhodiola rosea, Astragali Radix, Polygonati Rhizoma, Lycii Fructus), compound Rhodiola Rosea water extract group, compound Astragalus alcohol-water extract group (Astragali Radix, Polygonati Rhizoma, Lycii Fructus) and compound Astragalus water extract group, 30 mice in each group. Each group was administered continuously by gavage for 10 d. The blank group was gavaged with sterilized injection water. The mice in the other groups were treated with 0.15 g/kg of compound danshen, 3 g/kg of compound Rhodiola Rosea alcohol-water extract or water extract, and 1.7 g/kg of compound Astragalus alcohol-water extract or water extract, respectively. Each group was subjected to normobaric hypoxia tolerance test, sodium nitrite toxicity survival test and acute cerebral ischemia-hypoxia test 1 h after the last gavage, and the mice brain tissues were used to determine the activity of antioxidant enzymes and metabolites related to oxidative stress. Results: Compared with the blank control group, in normobaric hypoxia tolerance test, the survival time of mice in the compound danshen group and the compound Astragalus alcohol-water extract group and water extraction group was prolonged significantly (P＜0.01), and the number of open-mouth gasping after cerebral ischemia and hypoxia was increased significantly (P＜0.05). There was no statistical difference in survival time after sodium nitrite injection in each group. Compared with the blank control group, the activities of T-AOC, SOD, GSH and CAT were increased significantly (P＜0.05, P＜0.01) and the content of MDA was decreased significantly (P＜0.01) in the compound Astragalus water extract group. Compared with the compound danshen group, the activities of SOD, CAT and GSH were increased significantly (P＜0.01, P＜0.05) and the content of MDA was decreased significantly (P＜0.05). Conclusion: Compound Astragalus water extraction has the best effect of hypoxia tolerance, compound Rhodiola Rosea can eliminate Rhodiola rosea and consists of Astragali Radix, Polygonati Rhizoma, Lycii Fructus and its extraction method is water extraction.

Protective effect of 5,6,7,8-Tetrahydroxyflavone on high altitude cerebral edema in rats.

High altitude cerebral edema (HACE) is a potentially life-threatening disease encountered at high altitudes. However, effective methods for HACE prophylaxis are limited. Convincing evidence confirms that oxidative stress induced by hypobaric hypoxia (HH) is one of the main factors that account for the development of HACE. 5,6,7,8-Tetrahydroxyflavone (THF), a flavone with four consecutive OH groups in ring A, exhibited excellent antioxidant activity in vitro and could attenuate HH induced injury in vivo. The aim of this study was to investigate the protective effect of THF against HACE and its underlying mechanisms. THF administration significantly suppressed HH induced oxidative stress by reducing the formation of hydrogen peroxide and malondialdehyde, by increasing the levels of glutathione and superoxide dismutase in brain tissue. Simultaneously, THF administration inhibited inflammatory responses by decreasing the levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in serum and brain tissue. In addition, THF administration mitigated the energy metabolism disorder induced by HACE as evidenced by decreased levels of lactic acid, lactate dehydrogenase and pyruvate kinase as well as increased ATP levels and ATPase activities. Furthermore, THF administration decreased the expression of matrix metalloproteinase-9, aquaporin 4, hypoxia-inducible factor-1α and vascular endothelial growth factor, which attenuated blood-brain barrier (BBB) disruption and brain edema. Additionally, THF administration improved HACE induced cognitive dysfunction. These results show that THF is a promising agent in the prevention and treatment of HACE.

The interdependent relationship between the nitric oxide signaling pathway and primary cilia in pulse electromagnetic field-stimulated osteoblastic differentiation.

Pulsed electromagnetic fields (PEMFs) have long been recognized being safe and effective in treating bone fracture nonunion and osteoporosis. However, the mechanism of osteogenic action of PEMFs is still unclear. While primary cilia are reported to be a sensory organelle for PEMFs, and nitric oxide (NO) plays an indispensable role in osteogenic effect of PEMFs, the relationship between NO and primary cilia is unknown. In this study, effects of treatment with 50 Hz 0.6 mT PEMFs on osteogenic differentiation and mineralization, NO secretion, and ciliary location of specific proteins were examined in rat calvarial osteoblasts (ROBs) with normal or abrogated primary cilia. It was found that PEMFs stimulated the osteogenic differentiation by activating the NOS/NO/sGC/cGMP/PKG signaling pathway, which need the existence of primary cilia. All components of the signaling pathway including iNOS, eNOS, sGC, PKG-1, and PKG-2 were localized to primary cilia, and eNOS was phosphorylated inside the primary cilia. Besides, primary cilia were elongated significantly by PEMF treatment and changed dynamically with the activation NO/cGMP pathway. When the pathway was blocked by L-NAME, PEMFs could no longer elongate the primary cilia and stimulate the osteoblastic differentiation. Thus, this study for the first time observed activation of the NO/cGMP signaling pathway in ciliary compartment of osteoblasts, and PEMFs could not stimulate the osteoblastic differentiation if the NO signaling pathway was blocked or the ciliogenesis was inhibited. Our findings indicate the interdependent relationship between NO and primary cilia in the PEMF-promoted osteogenesis.

A novel nitronyl nitroxide radical HPN-C6 attenuates brain damage in an acute hypobaric hypoxia mouse model through inhibition of the oxidative stress.

Hypobaric hypoxia (HH) results in the increased formation of ROS and induces a wide range of deleterious effects on the brain. Nitronyl nitroxide radicals are a kind of stable organic nitroxide radicals with a good ability to scavenge ROS. Herein, a series of new nitronyl nitroxide radicals was synthesized according to the previous method. Among them, a compound with six carbon atoms alkyl chain (HPN-C6) was screened for estimating the protective effect against HH-induced brain injury in the acute HH mouse model. The results showed that HPN-C6 ameliorated oxidative stress by decreasing the activity of LDH and the content of H2O2, NO, and MDA, increasing the activities of SOD, CAT and GSH-PX in the brain tissue of HH injured mice. Moreover, HPN-C6 exhibited an anti-inflammatory effect by reducing the level of IL-1ß, TNF-α, and IL-6 in the brains of mice after HH exposure through regulating the P38 MAPK signaling pathway. In addition, HPN-C6 exhibited the protection effect by inhibiting the release of mitochondrial cytochrome C, locking the activation of caspase-3, and downregulating the expression of Bax and upregulating the expression of Bcl-2. HPN-C6 pretreatment could inhibit the caspase-dependent mitochondria apoptosis pathway. These findings indicate that HPN-C6 is a potential therapeutic agent to prevent brain damage induced by HH.

Proteomic landscape subtype and clinical prognosis of patients with the cognitive impairment by Japanese encephalitis infection.

BACKGROUND: Cognitive impairment is one of the primary sequelae affecting the quality of life of patients with Japanese encephalitis (JE). The clinical treatment is mainly focused on life support, lacking of targeted treatment strategy. METHODS: A cerebrospinal fluid (CSF) proteomic profiling study was performed including 26 patients with JE in Gansu province of China from June 2017 to October 2018 and 33 other concurrent hospitalized patients who were excluded central nervous system (CNS) organic or CNS infection diseases. The clinical and proteomics data of patients with JE were undergoing combined analysis for the first time. RESULTS: Two subtypes of JE associated with significantly different prognoses were identified. Compared to JE1, the JE2 subtype is associated with lower overall survival rate and a higher risk of cognitive impairment. The percentages of neutrophils (N%), lymphocyte (L%), and monocytes (M%) decreased in JE2 significantly. CONCLUSIONS: The differences in proteomic landscape between JE subgroups have specificity for the prognosis of cognitive impairment. The data also provided some potential target proteins for treatment of cognitive impairments caused by JE. Trial registration ChiCTR, ChiCTR2000030499. Registered 1st June 2017, http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=6333.

Design, synthesis and anti-hypoxia activity of HPN derivatives containing lipophilic long chains.

OBJECTIVE: To design and synthesize long-chain substituted 2-[(4'-hydroxyethoxy) phenyl]-4,4,5,5-tetramethyl-2-imidazoline-1-oxyl 3-oxide (HPN) derivatives with enhanced anti-hypoxic activity. METHODS: HPN derivatives 1, 3, 5 containing lipophilic long chains were synthesized via the alkylation of HPN with 6-bromohexan-1-ol, ethyl 6-bromohexanoate or 6-bromohexane, respectively using acetonitrile as the solvent and K 2CO 3 as the acid-binding agent at 60 ℃. Derivative 2 was synthesized via hydrolysis reactions of derivative 1 in the NaOH/CH 3OH/H 2O system. Using dichloromethane as the solvent and N, N'-diisopropylcarbodiimide as the dehydrating agent, HPN underwent esterification with hexanoic acid to obtain derivative 4. The structures of derivatives 1-5 were characterized by infrared spectroscopy, electron paramagnetic resonance and high resolution mass spectrometry. The purities of derivatives were detected by high performance liquid chromatography, and the lipid solubilities of derivatives were evaluated by calculating the oil-water partition coefficients (log P). Anti-hypoxia activities of HPN and its long-chain lipophilic derivatives 1-5 were evaluated using normobaric hypoxia test and acute decompression hypoxia test. RESULTS: The structures of the derivatives were confirmed by infrared spectroscopy, electron paramagnetic resonance and high resolution mass spectroscopy. The yields of target derivatives were all above 92%, and the purities were all above 96%. The log P values of derivatives 1-5 were 2.78, 2.00, 2.04, 2.88 and 3.10, which were higher than that of HPN (0.97). Derivatives 1-5 significantly prolonged the survival time of mice at the dose of 0.3 mmol/kg in normobaric hypoxic test and reduced the mortality rate of acute decompression hypoxic mice to 60%, 70%, 60%, 70% and 40%, respectively. CONCLUSIONS: The synthesis of derivatives 1-5 is convenient, and the yield is high. The synthesized derivatives especially derivative 5 show anti-hypoxic activity similar to or better than HPN at lower doses.

LRP8, modulated by miR-1262, promotes tumour progression and forecasts the prognosis of patients in breast cancer.

This research was designed to detect the function of low-density lipoprotein receptor (LDLR)-related protein 8 (LRP8) in breast cancer (BC). Our results revealed that LRP8 was highly expressed in BC tissues and cell lines compared with human normal breast tissues. The poor prognosis of patients with BC was associated with the up-regulation of LRP8 while inversely connected with overexpression of miR-1262. Functionally, LRP8 depletion in BC cells impaired the proliferative, clonogenic, invasive, and migratory capabilities, which was consistent with the effects of upregulated miR-1262. Bioinformatics prediction and luciferase reporter assay confirmed that miR-1262 was an upstream factor for LRP8 and negatively regulated the expression of LRP8. Further experiments illustrated that the co-transfection of miR-1262 antamir and si-LRP8 could significantly suppress the promoting impacts caused by the transfection of miR-1262 antamir alone. These findings highlighted that LRP8 accelerated the BC development by contributing cellular aggressiveness, which was modulated by miR-1262.

Protective effect of 5,6,7,8-trtrahydroxyflavone against acute hypobaric hypoxia induced-oxidative stress in mice.

Severe oxidative stress triggered by acute hypobaric hypoxia (AHH) is harmful for lots of organs in body, especial brain and heart. Flavonoids with antioxidant properties can protect organs from oxidative stress. Our previous study found that 5,6,7,8-trtrahydroxyflavone (5,6,7,8-THF), a flavones with four consecutive hydrogen group on ring A, showed excellent antioxidant properties in vitro. In the present study, the protective of 5,6,7,8-THF against oxidative stress caused by AHH was investigated. Mice were administered with 5,6,7,8-THF(500mg/kg) for 5 consecutive days before HH exposure. The heart rate (HR) and blood pressure (BP) was measured. The activity of SOD, CAT, GSH-Px, LDH, Na+-K+-ATPase and Ca2+-Mg2+-ATPase and the content of H2O2, MDA, LD and ATP in brain and heart tissue was evaluated using commercial kit. AHH led to a significant increase in HR and decrease in BP. Pretreatment of 5,6,7,8-THF could reversed these changes. In addition, administration of 5,6,7,8-THF could significantly increase the activity of SOD, CAT and GSH-Px and decrease the content of H2O2 and MDA in the brain and heart of mice under AHH. Furthermore, 5,6,7,8-THF inhibited the activity of LDH, decreased the level of LD and improved ATPase activity. These results indicate that 5,6,7,8-THF may protect the mice against AHH injury via scavenging free radical, inhibiting lipid peroxidation, enhancing antioxidant enzyme activity, preserving energy metabolism and can be further explored as an excellent anti-hypoxia agent for preventing acute mountain sickness.