The risk factors of new-onset atrial fibrillation after pacemaker implantation.

OBJECTIVE: The aim of this study was to determine the incidence of newly detected atrial fibrillation (AF) in patients following dual-chamber pacemaker (PPM) implantation and to define the clinical predictors of new-onset AF in a Chinese cohort. METHODS: A total of 219 patients without documented AF that underwent dual-chamber PPM implantation for sick sinus syndrome (SSS) (n = 88) or atrioventricular block (AVB) (n = 131) were prospectively studied. All patients were invited to follow-up at 1 month, 3 months and 6 months after the pacemaker implantation procedure, and once every 6 months thereafter. An atrial high-rate episode (AHRE) ≥5 min and an atrial rate ≥180 bpm was defined as AF. RESULTS: During follow-up of 884 ± 180 days, AF was detected in 56 (26%) patients. Using Kaplan-Meier survival curves with Log-rank test, SSS patients with a cumulative percentage of ventricular pacing (Cum % VP) ≥60% had a significantly higher rate of new-onset AF compared to AVB patients (p = 0.026) and SSS patients with Cum % VP <60% (p = 0.018). On multivariate Cox regression analysis, higher Cum % VP independently predicted higher morbidity of newly detected AF (hazard ratio [HR] 1.01; confidence interval [CI] 1.00 ~ 1.02; p = 0.035) among SSS patients. Larger left atrial (LA) dimension was a predictor of newly detected AF (HR 1.06; CI 1.01 ~ 1.14; p = 0.046) in AVB patients. CONCLUSION: The incidence of AF following dual-chamber PPM implantation was relatively high in this Chinese cohort. High Cum % VP and larger LA dimension could independently predict new-onset AF after dual-chamber PPM implantation in SSS and AVB patients, respectively.

One new spirocyclic lactone and one new benzopyran derivative from Aspergillus terreus.

One new spirocyclic lactone, terreinlactone C (1), and one new benzopyran derivative, 2,2-dimethyl-3-hydroxychroman-6-aldehyde (2), were discovered from the fungus Aspergillus terreus. The chemical structures of compounds 1 and 2 were elucidated by detailedly analyzing NMR and HRESIMS data. Compound 1 is the first natural product with a 1-oxaspiro[4.5]decan-2-one ring system and a possible biogenetic pathway is proposed. Two compounds were tested for their cytotoxic activities against five human cancer cell lines.[Formula: see text].

Amiaspochalasins A-H, Undescribed Aspochalasins with a C-21 Ester Carbonyl from Aspergillus micronesiensis.

Amiaspochalasins A-H (1-8), eight undescribed aspochalasins, and trichalasin D (9), a known analogue, were isolated from the solid culture of Aspergillus micronesiensis. Compounds 1-9 are aspochalasins with a C-21 ester carbonyl, and their structures were determined by spectroscopic data, X-ray crystallographic analyses, electronic circular dichroism calculations, and chemical methods. The CH3-25 in compound 1 is located at C-16 rather than C-14 in the previously reported aspochalasins, endowing 1 with an unexpected carbon skeleton. Compounds 2 and 3 are the first examples of aspochalasins with an unprecedented 5/6/6/8 tetracyclic ring system. Compounds 4 and 5 are diastereomers of aspochalasins I and J, respectively. Compounds 6 and 7 are the first aspochalasins featuring a long open-chain system, and their absolute configurations were discussed by comparing the NMR data of the hydrolysis and methyl esterification products of 4 and 5. Compound 8 is an isomeride of 9. The cytotoxic and antimicrobial effects of 1-9 were tested.

Flavipesines A and B and Asperchalasines E-H: Cytochalasans and Merocytochalasans from Aspergillus flavipes.

Flavipesines A and B (1 and 2) and asperchalasines E-H (3-6), two cytochalasans with an unusual ring system and four merocytochalasans possessing a 5/6/11/5/5/6 ring system, were isolated from Aspergillus flavipes, along with three related compounds (7-9). Their structures, including absolute configurations, were determined on the basis of data from HRESIMS, NMR, ECD, molecular modeling, and single-crystal X-ray diffraction. Flavipesines A and B (1 and 2) represent the first examples of cytochalasans possessing a 5/6/7/6 ring system with a C-18-O-C-21 bridge. Compounds 3, 7, and 9 show moderate inhibitory activities against isocitrate dehydrogenase 1 (IDH1). This is the first report on the IDH1 inhibitory activities of cytochalasans.

Cysteine Residue Containing Merocytochalasans and 17,18-seco-Aspochalasins from Aspergillus micronesiensis.

Two cysteine residue containing merocytochalasans (cyschalasins A and B, 1 and 2) and two 17,18-seco-aspochalasins (secochalasins A and B, 3 and 4) were isolated from the endophytic fungus Aspergillus micronesiensis. Cyschalasins A and B represent a new type of merocytochalasan featuring the fusion of an aspochalasin with a modified cysteine residue. Secochalasins A and B are the first 17,18-seco-aspochalasins to be reported and represent a previously undescribed carbon skeleton. Plausible biosynthetic pathways of 1-4 were proposed. Compounds 1 and 2 were cytotoxic and active against Gram-positive bacteria.

Dibrefeldins A and B, A pair of epimers representing the first brefeldin A dimers with cytotoxic activities from Penicillium janthinellum.

Dibrefeldins A and B (1 and 2), two unexpected brefeldin A (BFA) dimers, as well as brefeldin F (3), brefeldin G (4), and 14-hydroxy-BFA (5), three new BFA derivatives, together with three new naturally occurring BFA derivatives (6-8) and four known analogues (9-12), were isolated from the fungus Penicillium janthinellum. Dibrefeldins A and B (1 and 2) represent the first examples of BFA dimers formed by an esterification between two BFA monomer units. Brefeldin F (3) has an α,ß-unsaturated γ-lactone ring, and this moiety was first discovered in naturally occurring BFA derivatives. The structures and relative/absolute configurations of these derivatives were elucidated by extensive spectroscopic methods, 13C NMR calculations, and single-crystal X-ray diffraction. Compounds 1, 2, 8, and 9 showed excellent cytotoxic activities against six cancer cell lines with IC50 values ranging from 0.01 to 4.45 µM.

(±)-Terreinlactone A, a Pair of 3-Substituted δ-Lactone Enantiomers Derived from Terrein from the Fungus Aspergillus terreus.

Terreinlactone A (1a/1b), a pair of 3-substituted δ-lactone enantiomers, and terreinlactone B (2), a new biosynthetic intermediate of 1a/1b, were isolated from Aspergillus terreus, along with their biosynthetic precursor (+)-terrein (3) and (+)-isoterrein (4). Compounds 1a and 1b were separated by using a Daicel chiral-pak ASH column eluting with n-hexane-EtOH (80 : 20). The structures of 1a/1b with absolute configurations were determined by comprehensive spectroscopic analyses and electronic circular dichroic (ECD) calculations. Terreinlactone A (1) represents the first example of 1,5-seco-terrein and a biogenetic pathway is proposed from the precursor terrein via the intermediated terreinlactone B (2).

Neolignans with a Rare 2-Oxaspiro[4.5]deca-6,9-dien-8-one Motif from the Stem Bark of Cinnamomum subavenium.

Two pairs of racemic spirodienone neolignans with a rare 2-oxaspiro[4.5]deca-6,9-dien-8-one motif, named (±)-subaveniumins A (1) and B (2), were isolated from the bark of Cinnamomum subavenium. The chiral separation of the (+)-1, (-)-1, (+)-2, and (-)-2 enantiomers was accomplished via high-performance liquid chromatography on a chiral column. Their structures were elucidated using single-crystal X-ray diffraction and spectroscopic analyses (UV, IR, HRESIMS, and 1D and 2D NMR). The absolute configurations of the enantiomers were determined by comparing the experimental and calculated electronic circular dichroic spectra. The (+)-1, (-)-1, (+)-2, and (-)-2 enantiomers exhibited moderate inhibitory effects against NO production in RAW264.7 mouse macrophages induced by lipopolysaccharide, with IC50 values of 17.9, 5.6, 15.1, and 4.3 µM, respectively.

A rare case of watery diarrhea, hypokalemia and achlorhydria syndrome caused by pheochromocytoma.

BACKGROUND: A rare syndrome of watery diarrhea, hypokalemia and achlorhydria (WDHA) is usually caused by pancreatic endocrine tumors that secrete excessive vasoactive intestinal polypeptide (VIP). Here we report a rare case of WDHA caused by a pheochromocytoma. CASE PRESENTATION: A 45-year old male presented with persistent and progressive watery diarrhea for half a year, and was treated with dialysis due to azotemia, hypokalemia, hypercalcemia and metabolic acidosis. A right adrenal mass was found by ultrasonography, and Positron Emission Tomography-Computed Tomography (PET-CT) showed the tumor was hyper-metabolic. Levels of plasma normetanephrine (NMN) and serum chromogranin A (CgA) were significantly elevated. Immunohistochemistry analysis of the adrenal tumor was strongly positive for CgA, synaptophysin and VIP. The patient fully recovered from WDHA syndrome soon after surgery, as reflected in that diarrhea stopped, levels of plasma NMN, serum CgA, and electrolytes returned to normal thus no dialysis was needed. The patient remained disease free in a 12-months follow-up period. CONCLUSION: We report an extremely rare case of pheochromocytoma causing WDHA syndrome and uremia, which the patient completely recovered from after tumor resection.

[Selective arterial occlusion in the treatment of placenta percreta in late trimester of pregnancy].

OBJECTIVE: To evaluate the value of selective arterial occlusion in the treatment of placenta percreta in late trimester of pregnancy. METHODS: Fifteen clinical patients ( gestational age ≥34 weeks), diagnosed with placenta percreta in Xiangya Hospital of Central South University from January 2003 to December 2010, were retrospectively analyzed. According to whether the selective arterial occlusion was used or not, the 15 patients were divided into 2 groups: an arterial occlusion group (n=8) and a non-arterial occlusion group (n=7). Based on the time of occlusion, the arterial occlusion group was divided into a prophylactic occlusion subgroup (n=4) and a remedial occlusion subgroup (n=4) (including 1 patient who was performed after the iliac artery balloon was taken out ). The blood loss, the rate of hysterectomy and complications were compared between the arterial occlusion group and the non-arterial occlusion group. RESULTS: In all 15 patients, the average amount of blood loss was 3813 mL, and the rate of hysterectomy was 73.3% (11/15). The recent complication rate was 20.0% (3/15, including 2 blood coagulation dysfunctions and 1 lower extremity thrombosis), and long-term complication was not found. The average amount of blood loss in the occlusion group was 2512 mL, the hysterectomy rate was 62.5%(5/8); while the average amount of bleeding was 5549 mL and the hysterectomy rate was 85.7% in the non-occlusion group (6/7). There was significant difference between the 2 groups (P<0.05). The average amount of blood loss and the rate of hysterectomy in the prophylactic occlusion subgroup were lower than those in the remedial occlusion subgroup (1350 mL vs 3600 mL, 60.0% vs 66.7%, P<0.05). CONCLUSION: Patients with placenta percreta in the third trimester of pregnancy may encounter severe postpartum hemorrhage, and the rate of hysterectomy is high. The amount of blood loss and the rate of hysterectomy may be reduced by the selective arterial occlusion before or in the cesarean section, but cannot be avoided completely.

Mesoporous Activated Biochar from Crab Shell with Enhanced Adsorption Performance for Tetracycline.

In this study, three mesoporous-activated crab shell biochars were prepared by carbonation and chemical activation with KOH (K-CSB), H3PO4 (P-CSB), and KMnO4 (M-CSB) to evaluate their tetracycline (TC) adsorption capacities. Characterization by SEM and a porosity analysis revealed that the K-CSB, P-CSB, and M-CSB possessed a puffy, mesoporous structure, with K-CSB exhibiting a larger specific surface area (1738 m2/g). FT-IR analysis revealed that abundant, surface ox-containing functional groups possessed by K-CSB, P-CSB, and M-CSB, such as -OH, C-O, and C=O, enhanced adsorption for TC, thereby enhancing their adsorption efficiency for TC. The maximum TC adsorption capacities of the K-CSB, P-CSB, and M-CSB were 380.92, 331.53, and 281.38 mg/g, respectively. The adsorption isotherms and kinetics data of the three TC adsorbents fit the Langmuir and pseudo-second-order model. The adsorption mechanism involved aperture filling, hydrogen bonding, electrostatic action, π-π EDA action, and complexation. As a low-cost and highly effective adsorbent for antibiotic wastewater treatment, activated crab shell biochar has enormous application potential.

Downregulation of hsa_circ_0004543 Activates oxLDL-Induced Vascular Endothelial Cell Proliferation and Angiogenesis.

Circular RNAs (circRNAs) are novel non-coding RNAs, which show abnormal expression in several diseases, such as atherosclerosis (AS). The purpose of the present study was to reveal the association between hsa_circ_0004543 and AS. In the present study, hsa_circ_0004543 was overexpressed in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (oxLDL). Inhibition of hsa_circ_0004543 expression facilitated the proliferation, migration, and invasion of HUVECs and significantly reduced their apoptotic rate following treatment with oxLDL. Furthermore, silencing of hsa_circ_0004543 activated the PI3K/AKT/NOS3 pathway in oxLDL-induced HUVECs. Collectively, these results demonstrated that hsa_circ_0004543 may play a vital role in the development of AS and affect the proliferation of HUVECs, providing a potential target for treating endothelial cell damage in AS.

SIRT3 is a downstream target of PPAR-α implicated in high glucose-induced cardiomyocyte injury in AC16 cells.

Diabetic cardiomyopathy (DCM) is a worldwide public health concern that continues to display rapid growth trends. This study investigated the function of sirtuin 3 (SIRT3), a primary mitochondrial deacetylase with important roles in antioxidant defense and oxidative metabolism, during high glucose-induced cardiomyocyte (AC16 cell) injury. Peroxisome proliferator-activated receptor-α (PPAR-α) is directly related to the occurrence of DCM. Hence, we further examined the relationship between SIRT3 and PPAR-α. AC16 cells were treated with various concentrations of glucose. Relative mRNA expression and protein levels were detected by RT-qPCR and western blot analysis, respectively. Cell proliferation and apoptosis were assessed using CCK8 and Annexin V-FITC apoptosis detection kits, respectively. DCFH-DA assay was used to measure reactive oxygen species (ROS) accumulation. The results indicated that high glucose treatment reduced the expression of mRNA and protein of SIRT3 and PPAR-α in AC16 cells. Moreover, high glucose inhibited cell proliferation, as well as induced apoptosis, intracellular hydrogen peroxide production, and JNK1/2 phosphorylation. These effects were antagonized by SIRT3 overexpression or treatment with the PPAR-α agonist, Wy14643. Conversely, inhibition of SIRT3 via 3-TYP led to similar phenomena as those induced by high glucose treatment in AC16 cells, which were blocked by Wy14643. Lastly, chromatin immunoprecipitation (ChIP) and luciferase assays demonstrated SIRT3 as a direct target of PPAR-α. Taken together, the results provide evidence for an important role of SIRT3 in high glucose-induced cardiomyocyte injury and regulation of JNK1/2 signaling. Further, SIRT3 is a direct downstream target of PPAR-α.

Dimericchalasine A and Amichalasines D and E: Unexpected Cytochalasan Homodimer and Heterotrimers from Aspergillus micronesiensis PG-1.

The study of Aspergillus micronesiensis led to the isolation of three unprecedented cytochalasans (1-3). Dimericchalasine A (1) is the first cytochalasan homodimer fused by a C-20/C-20' single bond. Amichalasines D (2) and E (3) represent a new type of cytochalasan heterotrimer with a decacyclic 5/6/11/5/5/6/5/12/6/5 ring system. Their structures were determined by extensive spectroscopic data and single-crystal X-ray diffraction. The plausible biosynthetic pathways of 1-3 were proposed.

[Expression of NMBR in myometrium in pregnant mice at different gestational ages and its relation with parturition].

OBJECTIVE: To investigate the spatiotemporal expression of neuromedin B receptor (NMBR) in mice myometrium at different pregnant stages, as well as its mechanism and relation with parturition. METHODS: The pregnant mice were divided into no-pregnancy (NP), early pregnancy (EP), mid-pregnancy (MP), late-pregnancy (LP), parturition (PT) and postpartum (PP) groups (12 mice in each group), according to pregnant stage. The mRNA and protein expression of NMBR, HSP70 and IL-6 were detected in myometrium in pregnant mice by semi-quantitative RT-PCR and Western blot, while NF-kappaB-P65 DNA binding activity was determined by NoShift transcription factor assay kits, respectively. Their relation with parturition was analyzed. RESULTS: The mRNA expression level of NMBR in the PT group was significantly higher than that in the NP, EP, LP and PP groups (P<0.05), but this difference was not observed in the MP group (P>0.05). The NMBR protein in PT group was significantly higher than that in the other 5 groups (P<0.01). NF-kappaB-P65 DNA binding activity at PT group was remarkably higher than that in the NP, LP and PP groups (P<0.05). The expression of IL-6 mRNA was significantly higher than that in the NP, LP and PP groups (P<0.05), its protein expression in PT and LP groups was significantly higher than that in the NP and PP groups (P<0.05). The expression of HSP70 mRNA in the PT group was significantly higher than that in the NP and PP groups (P<0.05), and the protein of HSP70 was significantly up-regulated in PT and PP groups compared with in NP and LP groups (P<0.05). The DNA-binding activity of P65 was positively correlated to the mRNA expression of NMBR and IL-6 (r=0.40, P<0.01; r=0.30, P<0.05), so were positively correlated to DNA-binding activity of P65, mRNA expression of HSP70 and NMBR ( r=0.40, P<0.01; r=0.49, P<0.01). DNA-binding activity of P65 did not correlate with the mRNA expression of HSP70. CONCLUSION: The mRNA and protein expressions of NMBR reach a peak at the onset of labor. NMBR may play an important role in the parturition via NF-kappaB P65-IL-6 signal transduction pathway. It may also influence the onset of labor by regulating HSP70, but this role does not rely on P65 pathway.

Upregulation of miR-93 and inhibition of LIMK1 improve ventricular remodeling and alleviate cardiac dysfunction in rats with chronic heart failure by inhibiting RhoA/ROCK signaling pathway activation.

OBJECTIVE: There are some researches about the role of microRNA (miRNA) in chronic heart failure (CHF) were performed, but the study about miR-93's function in CHF is scarcely investigated. Thus, we determined to probe into the effects of miR-93 in rats with CHF by targeting LIMK1 through regulating RhoA/ROCK pathway. RESULTS: We found increased LIMK1 and decreased miR-93 in CHF rats, and up-regulation of miR-93 inhibited LIMK1, RhoA and ROCK1 expression in CHF rats. Up-regulation of miR-93 or inhibition of LIMK1 decreased oxidative stress, inflammatory factors, as well as apoptosis-related indicators in CHF rats. LIMK1 was confirmed as a direct target gene of miR-93. CONCLUSION: Our study provides evidence that upregulated miR-93 and downregulated LIMK1 improve ventricular remodeling and reduce cardiac dysfunction in CHF rats by inhibiting RhoA/ROCK signaling pathway activation. METHODS: First, rat models of CHF were established by aortic coarctation, and the rats were injected with miR-93 mimics, LIMK1-siRNA or overexpressed-LIMK1. Then expression of miR-93, LIMK1, RhoA, and ROCK1 expression in myocardial tissues were detected, after which indices of cardiac ultrasound, hemodynamics, and oxidative stress, inflammatory factors, apoptosis-related indicators were detected via a series of assays. Finally, the targeting relationship of miR-93 and LIMK1 was verified.

Amichalasines A-C: Three Cytochalasan Heterotrimers from Aspergillus micronesiensis PG-1.

Amichalasines A-C (1-3), which represent a new type of cytochalasan heterotrimers, were isolated from Aspergillus micronesiensis PG-1. Compounds 1 and 2 possess an undecacyclic 5/6/11/5/5/6/6/5/11/6/5 ring system, and 3 has an additional furan ring with a dodecacyclic 5/6/11/5/5/6/6/5/5/11/6/5 ring system. 1 and 2 exhibited potent cytotoxic activities through apoptosis induction mediated by caspase-3 activation and PARP degradation, and their IC50 values against HL60 cells were 1.71 and 3.74 µM, respectively.

Brasilane sesquiterpenoids and dihydrobenzofuran derivatives from Aspergillus terreus [CFCC 81836].

Brasilanones A-F and asperterreusines A-C, undescribed brasilane sesquiterpenoids and dihydrobenzofuran derivatives, were isolated from the marine-derived fungus Aspergillus terreus [CFCC 81836]. Their structures with absolute configurations were elucidated on the basis of spectroscopic data, X-ray crystallographic analyses, and electronic circular dichroism (ECD) calculations. Brasilanones A-F are unusual brasilane sesquiterpenoids with an α,ß-unsaturated ketone unit, interestingly, brasilanones B-D are stereo isomers. All of the isolates were evaluated for their inhibitory activities against NO production and cytotoxic activities against five human cancer cell lines (HL-60, SW-480, A-549, MCF-7, and SMMC-7721). Brasilanones A and E showed moderate inhibitory effect with NO inhibition rates of 47.7% (p < 0.001) and 37.3% (p < 0.001) at the concentration of 40 µM. Asperterreusines A showed cytotoxicity against HL-60 and SW-480 cell lines with IC50 values of 15.3 and 25.7 µM, respectively.

Phenylacetylene-bearing 3,4-seco-cleistanthane diterpenoids from the roots of Phyllanthus glaucus.

Three new cleistanthane diterpenoids, phyllanglins A-C (1-3), a new natural product, 4-acetyl-bergenin (4), and three known compounds (5-7) were isolated from the roots of Phyllanthus glaucus. Their structures were elucidated by extensive spectroscopic data analyses and single-crystal X-ray diffraction. Phyllanglins A-C were unusual cleistanthane diterpenoids with phenylacetylene moieties, and a plausible biogenetic pathway was proposed to discuss the origins of them. All of the isolates were evaluated for their anti-inflammatory activities.

[Scanning of drug targets related to uterus contraction from the uterine smooth muscles by cDNA microarray].

OBJECTIVE: To screen the differentially expressed gene profile from the smooth muscles in the fundus uterus at the active stage of labor, and to provide candidate genes for picking out the drug targets related to uterine contraction. METHODS: Differentially expressed genes of uterine smooth muscles in the corpus from pro and post spontaneous parturition and those induced by oxytocin,as well as those from the corpus and the lower portion spontaneous parturition,were scanned respectively by human full-length genetic cDNA microarray with 8064 probe sets. Semi-quantitative RT-PCR was applied to testify the expression of voltage dependent calcium channel-L subtype (CACNA). The differentially expressed genes in the structure and function of the drug targets were picked out by bio-informatics to serve as candidate drug targets related to uterine contraction. RESULTS: The expressions of 29 genes were upregulated in fundus smooth muscles from the pro and post natural parturition, the pro and post inductive parturition of oxytocin, and the natural parturition. The expression of CACNA gene in RT-PCR was in accordance with that in the microarray. Among the 29 genes, neuromedin B receptor (NMBR) gene and neuropeptide Y (NPY) gene were the genes which not only had the targets of uterine contracted medicine, but also could contract the uterine. The differential expression ratios of NMBR in the above 3 types of uterine myometrium were 6.9,11.3, and 9.0, respectively while those of NPY were 6.0,29.8, and 2.9 respectively. CONCLUSION: NMBR, whose expression in the uterine smooth muscles is always up-regulated at different parturition conditions, is likely to be an ideal candidate target of uterotonic drugs.