Statin-mediated reduction in mitochondrial cholesterol primes an anti-inflammatory response in macrophages by upregulating JMJD3.

Stains are known to be anti-inflammatory, but the mechanism remains poorly understood. Here we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the ATP synthase in the inner mitochondrial membrane (IMM) and changes the proton gradient in the mitochondria. This activates NFkB and Jmjd3 expression to remove the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus LPS (M1), both macrophages treated with statins in vitro or isolated from statin-treated mice in vivo, express lower levels pro-inflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.

Spin- and Valley-Dependent Electronic Structure in Silicene Under Periodic Potentials.

We study the spin- and valley-dependent energy band and transport property of silicene under a periodic potential, where both spin and valley degeneracies are lifted. It is found that the Dirac point, miniband, band gap, anisotropic velocity, and conductance strongly depend on the spin and valley indices. The extra Dirac points appear as the voltage potential increases, the critical values of which are different for electron with different spins and valleys. Interestingly, the velocity is greatly suppressed due to the electric field and exchange field, other than the gapless graphene. It is possible to achieve an excellent collimation effect for a specific spin near a specific valley. The spin- and valley-dependent band structure can be used to adjust the transport, and perfect transmissions are observed at Dirac points. Therefore, a remarkable spin and valley polarization is achieved which can be switched effectively by the structural parameters. Importantly, the spin and valley polarizations are greatly enhanced by the disorder of the periodic potential.

Plague in China 2014-All sporadic case report of pneumonic plague.

BACKGROUND: Yersinia pestis is the pathogen of the plague and caused three pandemics worldwide. Pneumonic plague is rarer than bubonic and septicemic plague. We report detailed clinical and pathogenic data for all the three sporadic cases of pneumonic plagues in China in 2014. CASE PRESENTATION: All the three patients are herders in Gansu province of China. They were all infected by Yersinia pestis and displayed in the form of pneumonic plague respectively without related. We tested patient specimens from the upper (nasopharyngeal swabs) or the lower (sputum) respiratory tract and whole blood, plasma, and serum specimens for Yersinia pestis. All patients had fever, cough and dyspnea, and for patient 2 and 3, unconscious. Respiratory symptoms were predominant with acute respiratory failure. The chest X-ray showed signs consistent with necrotizing inflammation with multiple lobar involvements. Despite emergency treatment, all patients died of refractory multiple organ failure within 24 h after admission to hospital. All the contacts were quarantined immediately and there were no secondary cases. CONCLUSIONS: Nowadays, the plague is epidemic in animals and can infect people who contact with the infected animals which may cause an epidemic in human. We think dogs maybe an intermediate vector for plague and as a source of risk for humans who are exposed to pet animals or who work professionally with canines. If a patient has been exposed to a risk factor and has fever and dyspnea, plague should be considered. People who had contact with a confirmed case should be isolated and investigated for F1 antigen analysis and receive post-exposure preventive treatment. A vaccination strategy might be useful for individuals who are occupationally exposed in areas where endemically infected reservoirs of plague-infected small mammals co-exist.

[Chemical constituents from leaves of Garcinia xanthochymus].

The constituents were isolated and purified by the silica gel and semi-preparative HPLC, and their structures were elucidated by NMR spectral and MS data. Fifteen compounds were isolated from the ethyl acetate fraction of 95% ethanol extract from the leaves of Garcinia xanthochymus, and identified as 5, 7, 4'-trihydroxy-6-(3-hydroxy-3-methylbutyl)-flavone(1), 1,5-dihydroxy-3-methoxyxanthone(2), 1, 3-dimethoxy-5-hydroxy xanthone(3), kaempferol(4),(2S,3S)-trans-dihydrokaempferol(5), 3, 24, 25-trihydroxytirucall-7-ene(6), 4-hydroxycinnamic acid(7), isovanillic acid(8),(Z)-2-(2,4-dihydroxy-2, 6, 6-trimethylcyclohexylidene)acetic acid(9), volkensiflavone(10), morelloflavone(11), 3, 8″-biapigenin(12), bilobetin(13), fukugiside(14), GB2a glucoside(15). Compound 1 is a new compound, compounds 5, 6, 9 and 13 are isolated from the genus Garcinia for the first time, and compounds 4, 7-8, 10-12, 14 and 15 are firstly found from this plant. α-Amylase inhibitory activities of 10 compounds were determined using starch azure as the substrate, and the results show that compound 13 has the inhibitory activities against α-amylase, IC50 values of compound 13 and acarbose are 8.12, 4.32 µmol•L⁻¹ respectively.

Four new lignans from Schisandra sphenanthera.

Three new 7,8-secolignans, schisandlignans A-C (1, 2, and 4), one new dibenzocyclooctadiene lignan, schisandlignan D (5), together with nine known lignans 3',4'-dimethoxybenzoic acid (3″,4″-dimethoxyphenyl)-2-methyl-3-oxobutyl ester (3), gomisin J (6), rubrisandrin A(1b) (7), interiotherin B (8), schisantherin D (9), ( - )-machilusin (10), ganschisandrine (11), henricine A (12), and (+)-1-hydroxy pinoresinol (13), were isolated from the rattan of Schisandra sphenanthera. Their structures were determined by analysis of 1D and 2D NMR spectroscopic data.

Critical influenza (H1N1) pneumonia: imaging manifestations and histopathological findings.

BACKGROUND: The global outbreak of influenza A (H1N1) has led to the Ministry of Health of China listing it as one of the A-class infectious diseases. Pneumonia is the most serious complication of influenza A, commonly causing death. Populations are ordinarily susceptible to influenza A. This study aimed to investigate the imaging manifestation features of critical influenza A (H1N1) pneumonia and to improve its diagnostic techniques. METHODS: A total of seven death cases from critical influenza A (H1N1) pneumonia were retrospectively analyzed on their imaging manifestations and autopsy data. Pulmonary CT scanning was performed for five cases, with one receiving additional chest X-ray and chest CT scanning, and chest postero-anterior position X-ray examination was performed for other two. Autopsy was performed for five cases and postmortem examinations were performed for other two cases. RESULTS: The seven cases of influenza A showed critical manifestations in 4 - 7 days after symptoms onset, with two having basic diseases of diabetes and one being pregnant. Extensive blurry high-density shadows of bilateral lungs were found in three cases, which were most obvious in middle and inferior parts of lungs. Pulmonary CT scanning revealed bilateral flaky parenchymal shadows in peripheral, dorsal and fundus segments of the middle-inferior parts of lungs, with one case of complicated pneumothorax, atelectasis and pleural effusion and another case of thin-walled cavity and dilated bronchi shadows in the superior parts of lungs. CONCLUSIONS: Diagnostic imaging is an important assessing tool for critical influenza A (H1N1) pneumonia. The imaging manifestations are characteristic instead of being specific. The definitive diagnosis can be made in combination with clinical examinations and laboratory tests.

[Terpenoids from Euphorbia antiquorum L.].

To study the chemical constituents of Euphorbia antiquorum L., the constituents were isolated with normal-phase and reverse-phase silica gel column chromatography and their structures were elucidated on the basis of spectroscopic data. Seven terpenoids were obtained from EtOAc extract of E. antiquoru L. They were identified as antiquorine A (1), antiquorine B (2), ent-13S-hydroxy-16-atisene-3,14-dione (3), taraxerol (4), 3beta-hydroxy-25,26,27-trisnorcycloart-24-oic acid (5), 9beta,19-cyclolanostan-3beta-ol (6) and psi-taraxastane-3,20-diol (7) by spectral analysis. Compounds 1-3 are diterpenoids, which belonged to abietane, ent-kaurane and atisane respectively. Among them, compounds 1 and 2 are new compounds. Compounds 4-7 are triterpenoids, and compound 5 is a degraded cycloartane triterpenoid which is a new natural product. Compound 7 was isolated from this plant for the first time. It demonstrated that the chemical structures of constituents in this plant were diverse.

Terpenoids and flavonoids from Laggera pterodonta.

To study the chemical constituents of aerial parts of Laggera pterodonta (DC.) Benth., the air-dried aerial parts of this plant were powered and extracted with boiling water and purified by silica gel column chromatography and recrystallized. Eleven compounds were obtained from L. pterodonta. They were identified as to be 6-O-beta-D-glucopyranosyl-carvotanacetone (1), pterodontic acid (2), 1beta-hydroxy pterondontic acid (3), pterodontoside A (4), pterodondiol (5), pterodontriol B (6), 5-hydroxy-3,4', 6,7-tetramethoxyflavone (7), artemitin (8), chrysosplenetin B (9), quercetin (10) and beta-sitosterol (11). Compound 1 is a new monoterpene glucoside. Compounds 10 and 11 were isolated from this plant for the first time. Compounds 2 and 5 showed moderate activity against bacteria including Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Mycobacteium phlei and Bacillus circulans by paper disc diffusion method, while they both displayed no activity against Escherichia coli.

Ca2+ participates in alpha1B-adrenoceptor-mediated cAMP response in HEK293 cells.

AIM: To investigate the alpha1B-adrenoceptor (alpha1B-AR)-mediated cAMP response and underlying mechanisms in HEK293 cells. METHODS: Full-length cDNA encoding alpha1B-AR was transfected into HEK293 cells using the calcium phosphate precipitation method, and alpha1B-AR expression and cAMP accumulation were determined by using the saturation radioligand binding assay and ion-exchange chromatography, respectively. RESULTS: Under agonist stimulation, alpha1B-AR mediated cAMP synthesis in HEK293 cells, and blockade by PLC-PKC or tyrosine kinase did not reduce cAMP accumulation induced by NE. Pretreatment with pertussis toxin (PTX) had little effect on basal cAMP accumulation as well as norepinephrine (NE)-stimulated cAMP accumulation. In addition, pretreatment with cholera toxin (CTX) neither mimicked nor blocked the effect induced by NE. The extracellular Ca2+ chelator egtazic acid (EGTA), nonselective Ca2+ channel blocker CdCl2 and calmodulin (CaM) inhibitor W-7 significantly reduced NE-induced cAMP accumulation from 1.59%+/-0.47% to 1.00%+/-0.31%, 0.78%+/-0.23%, and 0.90%+/-0.40%, respectively. CONCLUSION: By coupling with a PTX-insensitive G protein, alpha1BAR promotes Ca2+ influx via receptor-dependent Ca2+ channels, then Ca2+ is linked to CaM to form a Ca2+-CaM complex, which stimulates adenylyl cyclase (AC), thereby increasing the cAMP production in HEK293 cell lines.