Riligustilide Attenuated Renal Injury by the Blockade of Renin

Background/Aims: Nephropathy related with renin can be alleviated with ACE-inhibitors or AT1R blockers, whereas they might be ineffective after long-term administration because of a feedback production of enhanced renin. Therefore, it is urgent to develop a new category of anti-nephropathy medicine directly targeting renin. Riligustilide (C20), originally isolated from the Chinese herb Ligusticumporteri, a rhizome, was confirmed effective against many diseases. Methods: The therapeutic effect of C20 on renal injury and its underlying mechanism were investigated in three different nephrotic models, which were spontaneously hypertension rats (SHR) model, diabetic nephropathy in BTBR ob/ob mice model and 5/6-nephrectomized (5/6NX) rats model. Results: The intensity of kidney fibrosis was extensively decreased in the C20-treated rats compared to the vehicle animals. C20 significantly alleviated renal injury much more in 5/6 NX rats than in vehicle group. The rats in 5/6 NX without administrated C20 developed albuminuria earlier with more severe symptoms. Additionally, our findings showed that C20 down-regulated the renin expression and relocation of CREB-CBP complex in vivo and in vitro. Conclusion: C20 plays importantly reno-protective roles most likely through the relocation of CREB-CBP complex

Glucitol-core containing gallotannins-enriched red maple (Acer rubrum) leaves extract alleviated obesity via modulating short-chain fatty acid production in high-fat diet-fed mice

Glucitol-core containing gallotannins (GCGs) are characteristic constituents of the red maple (Acer rubrum) species. To pursue the development of red maple for nutraceutical applications, GCGs-enriched red maple leaves extract (MLE) was evaluated for its effects on obesity, gut dysbiosis and short chain fatty acids (SCFAs) production. Our results demonstrated that MLE alleviated high-fat diet-induced obesity, reduced body weight gain and fat mass, improved liver steatosis and insulin resistance, and mitigated adipose hypertrophy and inflammation. Additionally, MLE increased total SCFAs, acetic acid and n-butyric acid content, but exerted no impact on propionic acid production. Moreover, MLE modulated gut microbiota community structure and certain bacteria relative abundance, including Prevotella and Eubacterium. Our work firstly reports a potential association between colon-derived SCFAs production and metabolic improvement due to GCGs-enriched red maple leaves extract administration, and highlights the utilization of red maple gallotannins as a dietary ingredient for preventing obesity and related metabolic diseases

Antimicrobial and anti-inflammatory activity of four known and one new triterpenoid from Combretum imberbe (Combretaceae)

Please open article to read abstractWe thank our colleagues at the HKI department of Biomolecular Chemistry for providing spectral data. Financial support by the German Academic Exchange Service (DAAD, to J.E.A.), the German Ministry for Education and Research (BMBF, CHN 02/322), National Research Foundation and University of Pretoria is gratefully acknowledged

Cytotoxic Activities, SAR and Anti-Invasion Effects of Butylphthalide Derivatives on Human Hepatocellular Carcinoma SMMC7721 Cells

A series of butylphthalide derivatives (BPDs) 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp2 carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5

The Role of Copper Homeostasis in Brain Disease

In the human body, copper is an important trace element and is a cofactor for several important enzymes involved in energy production, iron metabolism, neuropeptide activation, connective tissue synthesis, and neurotransmitter synthesis. Copper is also necessary for cellular processes, such as the regulation of intracellular signal transduction, catecholamine balance, myelination of neurons, and efficient synaptic transmission in the central nervous system. Copper is naturally present in some foods and is available as a dietary supplement. Only small amounts of copper are typically stored in the body and a large amount of copper is excreted through bile and urine. Given the critical role of copper in a breadth of cellular processes, local concentrations of copper and the cellular distribution of copper transporter proteins in the brain are important to maintain the steady state of the internal environment. The dysfunction of copper metabolism or regulatory pathways results in an imbalance in copper homeostasis in the brain, which can lead to a myriad of acute and chronic pathological effects on neurological function. It suggests a unique mechanism linking copper homeostasis and neuronal activation within the central nervous system. This article explores the relationship between impaired copper homeostasis and neuropathophysiological progress in brain diseases

Catalpol Inhibits Amyloid-β Generation Through Promoting α-Cleavage of APP in Swedish Mutant APP Overexpressed N2a Cells

Amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer’s disease (AD), due to its neurotoxicity. Thus, blocking Aβ generation and aggregation in the brain has been realized as an efficient way for the prevention of AD. The natural product catalpol, isolated from Rehmannia glutinosa, has shown neuroprotective activities through inhibiting soluble Aβ production, degrading Aβ peptide, and attenuating Aβ toxicity and neuroinflammatory responses. In the present study, we aimed to evaluate whether catalpol reduce Aβ generation associated with regulating amyloid precursor protein (APP) proteolytic processing. By using Swedish mutant APP overexpressed N2a (SweAPP N2a) cells treated with catalpol, we found that catalpol was not able to reduce the expression levels of β-secretase (BACE-1) and γ-secretase (PS1, APH-1, PEN-2 and Nicastrin). By contrast, catalpol had a significant promotion effect on the expression of α-secretase (ADAM10) and its proteolytic products, sAPPα and C83, suggesting that catalpol reduced the production of Aβ might be involved in non-amyloidogenic APP pathway. In addition, we confirmed that the extracellular signal-related kinase/cAMP-response element binding protein (ERK/CREB) signaling pathways were responsible for the up-regulation of ADAM10 in catalpol-treated SweAPP N2a cells. The present data, for the first time, have demonstrated that the effect of catalpol on the inhibiting Aβ generation might be closely related to α-cleavage of APP processing

Maintenance Therapy with Immunomodulatory Drugs after Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials

<div><p>Background</p><p>Although high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) has been confirmed to result in longer remission time than conventional chemotherapy, multiple myeloma (MM) remains incurable. Post-ASCT maintenance is considered as a strategy for obtaining durable remissions and preventing tumor progression. Randomized controlled trials (RCTs) studying maintenance therapy with immunomodulatory drugs (IMiDs) after ASCT have shown some valuable survival improvements. This meta-analysis of RCTs therefore assesses the effect of post-ASCT IMiDs maintenance on MM patients.</p> <p>Methods</p><p>We performed a meta-analysis to evaluate the impact of IMiDs (thalidomide or lenalidomide) as post-ASCT maintenance therapy on the survival of newly diagnosed MM patients. The outcomes for this meta-analysis were progression-free survival (PFS) and overall survival (OS).</p> <p>Results</p><p>Eight RCTs enrolling 3514 patients were included for analysis. An obvious improvement in Os (hazard ratio [HR] 0.75) and a significant PFS advantage (HR 0.58) with post-ASCT IMiDs maintenance was revealed. Thalidomide maintenance after ASCT can result in significant benefit in Os (HR 0.72), particularly combined with corticosteroids (HR 0.66).</p> <p>Conclusions</p><p>MM patients after ASCT have a significant overall survival benefit with IMiDs maintenance. IMiDs maintenance was justified for MM patients who received HDT with ASCT.</p> </div

The effect of different screw-rod design on the anti-rotational torque: a biomechanical comparison of three conventional screw-rod constructs

Abstract Background Screw-rod constructs have been widely used to correct spinal deformities, but the effects of different screw-rod systems on anti-rotational torque have not been determined. This study aimed to analyze the biomechanical effect of different rod-screw constructs on anti-rotational torque. Methods Three conventional spinal screw-rod systems (Legacy, RF-F-10 and USSII) were used to test the anti-rotational torque in the material test machine. ANOVA was performed to evaluate the anti-rotational capacity of different pedicle screws-rod constructs. Results The anti-rotational torque of Legacy group, RF-F-10 group and USSII group were 12.3 ± 1.9 Nm, 6.8 ± 0.4 Nm, and 3.9 ± 0.8 Nm, with a P value lower than 0.05. This results indicated that the Legacy screws-rod construct could provide a highest anti-rotation capacity, which is 68% and 210% greater than RF-F-10 screw-rod construct and USSII screw-rod respectively. Conclusions The anti-rotational torque may be mainly affected by screw cap and groove design. Our result showed the anti-rotational torque are: Legacy system > RF-F-10 system > USSII system, suggesting that appropriate rod-screw constructs selection in surgery may be vital for anti-rotational torque improvement and preventing derotation correction loss

Synthesis of Seco-Chlorinated Derivatives of Phenanthroindolizidine Precursors via Friedel-Crafts Reaction

molecule

Meta-analysis of overall survival (OS) with IMiDs maintenance after ASCT.

<p>(<b>A</b>) OS with post-ASCT IMiDs maintenance. (<b>B</b>) OS with post-ASCT IMiDs maintenance, subgroup analysis according to thalidomide (Group 1) or lenalidomide (Group 2) as maintenance therapy. (<b>C</b>) OS with thalidomide maintenance, subgroup analysis according to non-IMiDs maintenance (Group 1) or no maintenance (Group 2) in the control arm. (<b>D</b>) OS with thalidomide maintenance, subgroup analysis according to corticosteroids combined with thalidomide (Group 1) or thalidomide alone (Group 2) as maintenance in the experimental arm. Abbreviations: IMiDs, immunomodulatory drugs.</p