Antibacterial metabolites from the beetle-associated fungus Penicillium chrysogenum.

The antibacterial secondary metabolites of the fungus Penicillium chrysogenum associated with the beetle Aspongopus chinensis were investigated through chromatographic fractionation methods of ethyl acetate extracts of the fungal cultures. Five compounds were isolated, and their structures were determined as emodin, 4-(methoxymethyl)benzoic acid, isoochracinic acid, secalonic acid D, and dicerandrol A using mass spectroscopy and nuclear magnetic resonance spectroscopic analyses. Emodin exhibited strong antimicrobial activity, especially against Staphylococcus aureus even when growing on cooked pork, with a minimal inhibitory concentration (MIC) of 6.3 µg/mL. Dimeric tetrahydroxanthones, such as secalonic acid D and dicerandrol A, also exhibited potent activity, with MIC values ranging from 9.5 to 28.5 µg/mL. In summary, P. chrysogenum was isolated as a symbiotic fungus of the beetle A. chinensis for the first time and this strain could generate antibacterial secondary metabolites, which could potently inhibit gram-positive bacteria growth in vitro.

Antibacterial and antioxidant metabolites from the insect-associated fungus Aspergillus fumigatus.

The research on bioactive secondary metabolites from Aspergillus fumigatus afforded six compounds, which were identified by mass spectrometer (MS) and nuclear magnetic resonance (NMR) spectroscopic analysis as cyclopyazonic acid (1), trypacidin A (2), asterric acid (3), methyl asterrate (4), demethylcitreoviranol (5), as well as (5-hydroxy-2-oxo-2H-pyran-4-yl) methyl acetate (6). Cyclopyazonic acid (1) was found to have potent antibacterial effects, especially against Bacillus licheniformis with minimal inhibitory concentration (MIC) value of 3.7µg/mL. Its antibacterial effects were possibly related to the olefinic acid group in the structure. Phenyl ether derivatives 3 and 4, and trypacidin A (2) also exhibited antimicrobial effects. In addition, compound 6 showed significant antioxidant effects with half maximal effective concentration (EC50) value of 10.2µM in the ABTS (2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) assay, which was better than the positive control.

Antioxidant epoxydon and benzolactone derivatives from the insect-associated fungus Phoma sp.

One new epoxydon ester (1) and a new benzolactone derivative (2), along with four known compounds (3-6), were isolated from the insect-associated fungus Phoma sp. Their structures were confirmed by extensive MS and NMR spectroscopic analysis and their absolute configurations were determined by a combination of modified Mosher method and Mo2(OCOCH3)4-induced electronic circular dichroism (ECD) experiments. Compounds 1 and 5 were revealed to have potent antioxidant activities, which were approximate to the potency of the positive control trolox. In addition, 1 also exhibited moderate cytotoxic effect against human MGC-803 tumor cell line.[Formula: see text].

Melatonin modulates daytime-dependent synaptic plasticity and learning efficiency.

Mechanisms of hippocampus-related memory formation are time-of-day-dependent. While the circadian system and clock genes are related to timing of hippocampal mnemonic processes (acquisition, consolidation, and retrieval of long-term memory [LTM]) and long-term potentiation (LTP), little is known about temporal gating mechanisms. Here, the role of the neurohormone melatonin as a circadian time cue for hippocampal signaling and memory formation was investigated in C3H/He wildtype (WT) and melatonin receptor-knockout ( MT 1 / 2 - / - ) mice. Immunohistochemical and immunoblot analyses revealed the presence of melatonin receptors on mouse hippocampal neurons. Temporal patterns of time-of-day-dependent clock gene protein levels were profoundly altered in MT 1 / 2 - / - mice compared to WT animals. On the behavioral level, WT mice displayed better spatial learning efficiency during daytime as compared to nighttime. In contrast, high error scores were observed in MT 1 / 2 - / - mice during both, daytime and nighttime acquisition. Day-night difference in LTP, as observed in WT mice, was absent in MT 1 / 2 - / - mice and in WT animals, in which the sympathetic innervation of the pineal gland was surgically removed to erase rhythmic melatonin synthesis. In addition, treatment of melatonin-deficient C57BL/6 mice with melatonin at nighttime significantly improved their working memory performance at daytime. These results illustrate that melatonin shapes time-of-day-dependent learning efficiency in parallel to consolidating expression patterns of clock genes in the mouse hippocampus. Our data suggest that melatonin imprints a time cue on mouse hippocampal signaling and gene expression to foster better learning during daytime.

Hybrid operation to revascularize long-segment occluded internal carotid artery prevent further ischemic events.

PURPOSE: The effects and complications of hybrid procedure (combined carotid endarterectomy and carotid stenting) to revascularize chronic long-segment occlusion of internal carotid artery (ICA) are currently unknown and the purpose of this study. METHODS: Sixty-five patients with long-segment occlusion of ICA were prospectively enrolled and divided into two groups of revascularization with hybrid operation (n = 30) and medication group (n = 35), and clinical and angiographic data were analyzed. RESULTS: The duration from symptom onset to revascularization ranged 17-120 days (mean 40.5 ± 5.0) in the hybrid operation, with a success revascularization rate of 100%. All patients had thrombi extracted with the clot length ranging 5-8 cm (mean 6.3 ± 0.9). The thrombolysis in cerebral infarction grade (TICI) was significantly (P < 0.0001) greater immediately after (median 2,) than before recanalization (0). Periprocedural complications included recurrent laryngeal nerve injury in one patient and intracranial hemorrhage in another (6.7%), but no severe neurological deficits occurred. The symptoms were significantly (P < 0.0001) improved after compared with before operation, with the modified Rankin score of 2.5 ± 0.6 at 3 months postoperation which was significantly (P < 0.0001) improved compared with before revascularization (3.4 ± 0.6). Follow-up angiography revealed patent ICA in all patients with hybrid operation. In the medication alone group, no significant (P > 0.05) improvement was observed with the mRS score of 3.5 ± 0.8 at admission and 3.4 ± 0.7 at 3 months, which was significantly (P < 0.001) greater than in the hybrid operation. CONCLUSION: Hybrid operation may be safe and effective in revascularizing long-segment occlusion of internal carotid artery for prevention of further ischemic events.

Association of Basilar Bifurcation Aneurysms With Age, Sex, and Bifurcation Geometry.

BACKGROUND AND PURPOSE: Basilar artery (BA) bifurcation aneurysms are common, but the correlation between BA bifurcation morphology and aneurysm formation remains to be established. Our purpose was to determine the association of BA bifurcation aneurysms with patient age, sex, bifurcation angle, and branch diameter. METHODS: Three-dimensional angiographic data of 195 patients were used, including 59 patients with BA bifurcation aneurysms and 136 control subjects. The angles formed between left and right posterior cerebral arteries (φ1) and between posterior cerebral artery and BA (the smaller angle defined as φ2 and the larger one as φ3), arterial diameters, and BA bifurcation aneurysm geometric characters were examined. RESULTS: Women of 40 to 70 years of age are more vulnerable to BA bifurcation aneurysm formation than men. The φ1 bifurcation angle significantly increased (P<0.0001), whereas both φ2 and φ3 angles significantly decreased (P<0.0001 and P=0.09, respectively) with increase of patients' age. Statistically significant (P<0.0001 and P=0.0002, respectively) positive correlations were observed between BA bifurcation branch diameter and aneurysm size. The φ1 angle was significantly (P<0.0001) wider in patients harboring BA bifurcation aneurysms than the control, whereas φ2 and φ3 angles in aneurysm group were significantly smaller than those in the control group (P<0.0001). The BA bifurcation aneurysms were mostly deviated toward the smaller φ2 angle side between φ2 and φ3 angles and deviated toward the smaller-diameter daughter posterior cerebral artery branch. CONCLUSIONS: BA bifurcation aneurysms are significantly associated with patients' age, female sex, wider bifurcation angles, and smaller vascular diameter at the BA bifurcation.

Hypoxia-Protective Azaphilone Adducts from Peyronellaea glomerata.

Peyronellones A and B (1 and 2), a pair of rare tetracyclic caged adducts of azaphilone with pyruvic acid, along with four new analogues (3-6), were isolated from solid cultures of the endophytic fungus Peyronellaea glomerata. Their structures were elucidated through spectroscopic analysis, and their absolute configurations were unambiguously determined by a combination of single-crystal X-ray crystallography, Rh2(OCOCF3)4-induced ECD experiments, ECD calculations, and modified Mosher methods. Compound 2 (5 µM) was found to have a significant hypoxia-protective effect that improved the survival rate of hypoxia/reoxygenation-treated human umbilical vein endothelial cells from 35% to 70%, which was equal to the potency of the positive control, verapamil. Flow cytometry analysis suggested 2 could inhibit H/R-induced late-stage apoptosis of this cell line.

In Vitro Antibiofilm Activity of Eucarobustol E against Candida albicans.

Formyl-phloroglucinol meroterpenoids (FPMs) are important types of natural products with various bioactivities. Our antifungal susceptibility assay showed that one of the Eucalyptus robusta-derived FPMs, eucarobustol E (EE), exerted a strong inhibitory effect against Candida albicans biofilms at a concentration of 16 µg/ml. EE was found to block the yeast-to-hypha transition and reduce the cellular surface hydrophobicity of the biofilm cells. RNA sequencing and real-time reverse transcription-PCR analysis showed that exposure to 16 µg/ml of EE resulted in marked reductions in the levels of expressions of genes involved in hyphal growth (EFG1, CPH1, TEC1, EED1, UME6, and HGC1) and cell surface protein genes (ALS3, HWP1, and SAP5). Interestingly, in response to EE, genes involved in ergosterol biosynthesis were downregulated, while the farnesol-encoding gene (DPP3) was upregulated, and these findings were in agreement with those from the quantification of ergosterol and farnesol. Combined with the obvious elevation of negative regulator genes (TUP1, NRG1), we speculated that EE's inhibition of carbon flow to ergosterol triggered the mechanisms of the negative regulation of hyphal growth and eventually led to biofilm inhibition.

Accuracy of computed tomographic angiography in the diagnosis of patients with inferior vena cava partial obstruction in Budd-Chiari syndrome.

BACKGROUND AND AIM: The diagnosis of the partially obstructed inferior vena cava (IVC) in Budd-Chiari syndrome (BCS) patients has received little attention. We aimed to evaluate the diagnostic accuracy of computed tomographic angiography (CTA) for patients with BCS and a partially obstructed IVC. METHODS: A total of 329 patients with BCS and an obstructed IVC were endovascularly treated with balloon dilation and/or stent placement. All patients underwent a CTA examination prior to endovascular treatment, and the data were retrospectively reviewed. The presence of a round, oval, irregular shape or jet sign low-density area without enhancement within the enhanced proximal IVC was considered a sign of a partially obstructed IVC. Digital subtraction angiography was used as the gold standard. RESULTS: The results from the digital subtraction angiography revealed a partially obstructed IVC in 108 BCS patients and a complete obstruction in 221 patients. The CTA discovered a partially obstructed IVC in 99 patients and a completely obstructed IVC in 230 patients. From the CTA results, 15 were false negatives, and six were false positives. The patient-based evaluation yielded an accuracy of 93.6%, a sensitivity of 86.1%, specificity of 97.3%, positive predictive value of 93.9%, and negative predictive value of 93.5% for the detection of BCS patients with a partial IVC obstruction. CONCLUSIONS: Computed tomographic angiography offered a high diagnostic accuracy and sensitivity in BCS patients with a partially obstructed IVC. The low-density area within the enhanced proximal IVC above the membrane in artery phase can be considered a reliable indicator of a stenotic IVC in BCS patients.

Outcomes of middle cerebral artery angioplasty and stenting with Wingspan at a high-volume center.

INTRODUCTION: This study was to investigate the periprocedural stroke rates, safety, and long-term effect of Wingspan stenting for symptomatic severe stenosis of the middle cerebral artery (MCA) at a high-volume center. METHODS: Between July 2007 and April 2013, 196 consecutive patients with severe MCA atherosclerotic stenosis (≥70%) who were treated with Wingspan stenting were retrospectively studied. All patients had arterial stenosis-related temporary ischemic attack or strokes. The demographic data, cerebral angiography, technical success rate, periprocedural complications, and clinical and imaging follow-up were analyzed. RESULTS: The successful stenting rate was 98.0%, and the stenosis rate was improved from pre-stenting (80.6 ± 8.3 %) to post-stenting (15.5 ± 6.8%). The 30-day periprocedural stroke or death rate was 7.1%, with a disabling or fatal rate of 2.6%. The perioprocedural stroke rate was significantly (P < 0.01) greater in the early learning stage (16.0%) than in the later technical maturation stage (4.1%). The total periprocedural ischemic and perforator stroke rates were greater in patients with the most stenosis in the distal MCA 1/3 segment (6.8 and 5.7%, respectively) than in the proximal and middle 2/3 segments (0.9 and 0%, respectively). The ipsilateral stroke or death rate beyond 30 days (6-69 months, mean 30 ± 16) was 4.8%, with the 1- and 2-year cumulative stroke rates of 9.6 and 12.1%, respectively. Imaging follow-up 6-69 months (mean 10.9 ± 8.5) revealed restenosis in 21 cases (20.4 %). CONCLUSION: Intracranial stenting of MCA stenoses may have the potential of better clinical outcomes if patients are properly selected and treated by an experienced operator at a high-volume center.