Significance of the lipid profile and endothelium-dependent vasodilatation in the pathogenesis of microvascular angina

Background: To investigate the significance of lipid disorders and endothelial dysfunction in the pathogenesis of microvascular angina. Methods: Levels of plasma lipids, lipoproteins and apolipoproteins were assessed in 21 patients with microvascular angina and 24 healthy subjects as controls. Also, the endothelium-dependent vasodilatation function was determined with high-resolution ultrasound in both groups. Results: Levels of serum total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), apolipoprotein B100 (ApoB100) and lipoprotein(a) [Lp(a)] in microvascular angina group were significantly higher than those in healthy subjects (each p < 0.05). The flow-mediated dilatation (FMD) in brachial arteries in patients with microvascular angina declined significantly as compared with that in control subjects (4.7 &#177; 1.9% vs. 12.8 &#177; 3.7%, p < 0.001). However, no significant difference was observed in response to nitroglycerin between groups (19.7 &#177; 8.1% vs. 21.2 &#177; 6.6%; p > 0.05). Linear correlation analysis revealed a significant negative correlation between the FMD of brachial arteries and the serum levels of LDL-C and Lp(a) in the microvascular angina group (r = -0.5125 and -0.4271, respectively, both p < 0.001). Subsequently, all subjects were pooled and divided into two groups (groups A and B) according to the degree of FMD in brachial arteries (A &#163; 4% and B > 4%). The serum LDL-C level was found to be significantly higher in group A than in group B (4.09 &#177; 0.65 mmol/L vs. 2.59 &#177; 0.49 mmol/L; p < 0.05). Conclusions: Plasma lipid disorders and vascular endothelial dysfunction may play important roles in the development of microvascular angina. The dysfunction of endothelium-dependent vasodilation was mainly associated with anomalies in LDL-C and Lp(a), and myocardial endothelial dysfunction was aggravated by lipid abnormalities in patients with microvascular angina

Molecular Mechanism of GTPase Activation at the Signal Recognition Particle (SRP) RNA Distal End

The signal recognition particle (SRP) RNA is a universally conserved and essential component of the SRP that mediates the co-translational targeting of proteins to the correct cellular membrane. During the targeting reaction, two functional ends in the SRP RNA mediate distinct functions. Whereas the RNA tetraloop facilitates initial assembly of two GTPases between the SRP and SRP receptor, this GTPase complex subsequently relocalizes ∼100 Å to the 5′,3′-distal end of the RNA, a conformation crucial for GTPase activation and cargo handover. Here we combined biochemical, single molecule, and NMR studies to investigate the molecular mechanism of this large scale conformational change. We show that two independent sites contribute to the interaction of the GTPase complex with the SRP RNA distal end. Loop E plays a crucial role in the precise positioning of the GTPase complex on these two sites by inducing a defined bend in the RNA helix and thus generating a preorganized recognition surface. GTPase docking can be uncoupled from its subsequent activation, which is mediated by conserved bases in the next internal loop. These results, combined with recent structural work, elucidate how the SRP RNA induces GTPase relocalization and activation at the end of the protein targeting reaction

The vital role of hole-carriers for superconductivity in pressurized black phosphorus

The influence of carrier type on superconductivity has been an important issue for understanding both conventional and unconventional superconductors [1-7]. For elements that superconduct, it is known that hole-carriers govern the superconductivity for transition and main group metals [8-10]. The role of hole-carriers in elements that are not normally conducting but can be converted to superconductors, however, remains unclear due to the lack of experimental data. Here we report the first in-situ high pressure Hall effect measurements on single crystal black phosphorus, measured up to ~ 50 GPa, and find a correlation between the Hall coefficient and the superconducting transition temperature (TC). Our results reveal that hole-carriers play a vital role in developing superconductivity and enhancing TC. Importantly, we also find a Lifshitz transition in the high-pressure cubic phase at ~17.2GPa, which uncovers the origin of a puzzling valley in the superconducting TC-pressure phase diagram. These results offer insight into the role of hole-carriers in developing superconductivity in simple semiconducting solids under pressure.Comment: 9 pages anf 3 figure

Pressure-induced melting of magnetic order and emergence of new quantum state in alpha-RuCl3

Here we report the observation of pressure-induced melting of antiferromagnetic (AFM) order and emergence of a new quantum state in the honeycomb-lattice halide alpha-RuCl3, a candidate compound in the proximity of quantum spin liquid state. Our high-pressure heat capacity measurements demonstrate that the AFM order smoothly melts away at a critical pressure (Pc) of 0.7 GPa. Intriguingly, the AFM transition temperature displays an increase upon applying pressure below the Pc, in stark contrast to usual phase diagrams, for example in pressurized parent compounds of unconventional superconductors. Furthermore, in the high-pressure phase an unusual steady of magnetoresistance is observed. These observations suggest that the high-pressure phase is in an exotic gapped quantum state which is robust against pressure up to ~140 GPa.Comment: 20 pages, 4 figure

Malignant Peritoneum Mesothelioma with Hepatic Involvement: A Single Institution Experience in 5 Patients and Review of the Literature

Malignant peritoneal mesothelioma with invasion of the liver is an invariably fatal disease. We aimed to clarify the characteristics of malignant peritoneal mesothelioma cases with liver involvement. The clinical presentation, computed tomography images, and immunohistochemical and histopathological features of 5 patients with malignant peritoneal mesothelioma and liver involvement were evaluated. The diagnosis was established by imaging and immune profiles of the tumours. A review of 8 cases with primary or invading malignant mesothelioma in liver is presented. All 5 mesothelioma cases were asbestos-related. CT images of malignant peritoneal mesothelioma with the liver involvement typically showed that the lesion grew inside the liver along the capsule and was possibly accompanied by capsule breakthrough and extrahepatic infiltration. The tumours exhibited a common epithelioid appearance in all 5 patients and most cases revealed positive Cal, CK, and MC with negative CEA and HeP. Different from our findings, the review of literature revealed that most malignant mesothelioma of liver was due to primary intrahepatic malignant mesothelioma. Finally, we concluded that the diagnosis of malignant peritoneal mesothelioma cases with liver invasion is reliably achieved by the history of asbestos exposure, the characteristic CT imaging, and immune profiles of the tumours

Kangfuxinye Enema Combined with Mesalamine for Ulcerative Colitis: A Systematic Review and GRADE Approach

Objectives. To critically appraise the efficacy and safety of Kangfuxinye enema combined with mesalamine for the ulcerative colitis (UC) patients and in addition to grade the quality of evidence by using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. Methods. A literature search was performed in the Cochrane Library, MEDLINE, EMBASE, CBM, CNKI, VIP, and WanFang Databases. The search restrictions were patients with UC and RCTs. Studies including other treatments except Kangfuxinye with mesalamine were excluded. Results. Nineteen studies met the inclusion criteria. We found significant benefits of Kangfuxinye combined with mesalamine against mesalamine alone in improving response rate as well as reducing the recurrence rate and inflammation rate; meanwhile, the increase of the adverse events rate was not observed. Furthermore, the symptoms remission rate and the cure time were insignificant statistically. Additionally, GRADE results indicated that the quality of evidence regarding the above 6 outcomes was rated from very low to moderate quality. Conclusions. Although Kangfuxinye enema seems effective and safe for treating UC patients in this systematic review, Kangfuxinye enema combined with mesalamine was weakly recommended due to very low to moderate quality of available evidence by the GRADE approach

Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway

Background/Aims: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion. Methods: LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP). Results: LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn’t show significant difference between PE and normal placentas. Conclusion: LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis