Early Major Worsening in Ischemic Stroke: Predictors and Outcome

Introduction: We aimed to investigate the characteristics and outcome of patients suffering early major worsening (EMW) after acute ischemic stroke (AIS) and assess the parameters associated with it. Methods: All consecutive patients with AIS in the ASTRAL registry until 10/2010 were included. EMW was defined as an NIHSS increase of ≥8 points within the first 24h after admission. The Bootstrap version of the Kolmogorov-Smirnov test and the χ 2-test were used for the comparison of continuous and categorical covariates, respectively, between patients with and without EMW. Multiple logistic regression analysis was performed to identify independent predictors of EMW. Results: Among 2155 patients, 43 (2.0%) had an EMW. EMW was independently associated with hemorrhagic transformation (OR 22.6, 95% CI 9.4-54.2), cervical artery dissection (OR 9.5, 95% CI 4.4-20.6), initial dysarthria (OR 3.7, 95% CI 1.7-8.0), and intravenous thrombolysis (OR 2.1, 95% CI 1.1-4.3), whereas a negative association was identified with initial eye deviation (OR 0.4, 95% CI 0.2-0.9). Favorable outcome at 3 and 12months was less frequent in patients with EMW compared to patients without (11.6 vs. 55.3% and 16.3 vs. 50.7%, respectively), and case fatality was higher (53.5 vs. 12.9% and 55.8 vs. 16.8%, respectively). Stroke recurrence within 3months in surviving patients was similar between patients with and without EMW (9.3 vs. 9.0%, respectively). Conclusions: Worsening of ≥8 points in the NIHSS score during the first 24h in AIS patients is related to cervical artery dissection and hemorrhagic transformation. It justifies urgent repeat parenchymal and arterial imaging. Both conditions may be influenced by targeted interventions in the acute phase of strok

Antiprotozoal activity of natural products from Nigerien plants used in folk medicine

In the course of the screening of plants from Niger for antiprotozoal activity, the methanol extract of Cassia sieberiana, and the dichloromethane extracts of Ziziphus mauritiana and Sesamun alatum were found to be active against protozoan parasites, namely Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and/or Plasmodium falciparum. Myricitrin (1), quercitrin (2) and 1-palmitoyl-lysolecithin (3) were isolated from C. sieberiana. From Z. mauritiana, the three triterpene derivatives 13, 15, and 16 are described here for the first time. Their chemical structures were determined by 1D and 2D NMR experiments, UV, IR and HRESIMS data. The absolute configurations were assigned via comparison of the experimental and calculated ECD spectra. In addition, eight known cyclopeptide alkaloids (4, 5, 7-12), and five known triterpenoids (6, 14, 17-19) were isolated. The antiprotozoal activity of the isolated compounds, as well as of eleven quinone derivatives (20-30) previously isolated from S. alatum was determined in vitro. The cytotoxicity in L6 rat myoblast cells was also evaluated. Compound 18 showed the highest antiplasmodial activity (IC(50) = 0.2 microm) and compound 24 inhibited T. b. rhodesiense with an IC(50) value of 0.007 microM. However, it also displayed significant cytotoxicity in L6 cells (IC(50) = 0.4 microm)

Isolation and structural elucidation of compounds from Pleiocarpa bicarpellata and their in vitro antiprotozoal activity

Species of the genus Pleiocarpa are used in traditional medicine against fever and malaria. The present study focuses on the isolation and identification of bioactive compounds from P. bicarpellata extracts, and the evaluation of their antiprotozoal activity. Fractionation and isolation combined to LC-HRMS/MS-based dereplication provided 16 compounds: seven indole alkaloids, four indoline alkaloids, two secoiridoid glycosides, two iridoid glycosides, and one phenolic glucoside. One of the quaternary indole alkaloids (7) and one indoline alkaloid (15) have never been reported before. Their structures were elucidated by analysis of spectroscopic data, including 1D and 2D NMR experiments, UV, IR, and HRESIMS data. The absolute configurations were determined by comparison of the experimental and calculated ECD data. The extracts and isolated compounds were evaluated for their antiprotozoal activity towards Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum, as well as for their cytotoxicity against rat skeletal myoblast L6 cells. The dichloromethane/methanol (1:1) root extract showed strong activity against P. falciparum (IC50 value of 3.5 microg/mL). Among the compounds isolated, tubotaiwine (13) displayed the most significant antiplasmodial activity with an IC50 value of 8.5 microM and a selectivity index of 23.4. Therefore, P. bicarpallata extract can be considered as a source of indole alkaloids with antiplasmodial activity

Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents

Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were isolated and identified from the fermentation broth of a marine-derived Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1, 2 and 3 inhibited TNF-α-induced NFκB activity (IC50 values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC50 values of >48.6, 15.1, and 8.0 μM, respectively). PGE2 production was blocked with greater efficacy (IC50 values of 7.5, 0.89, and 0.63 μM, respectively), possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2. Treatment of cultured HL-60 cells led to dose-dependent accumulation in the subG1 compartment of the cell cycle, as a result of apoptosis. These data provide greater insight on the biological potential of phenazine derivatives, and some guidance on how various substituents may alter potential anti-inflammatory and anti-cancer effects

Using metadynamics to explore complex free-energy landscapes

Metadynamics is an atomistic simulation technique that allows, within the same framework, acceleration of rare events and estimation of the free energy of complex molecular systems. It is based on iteratively \u2018filling\u2019 the potential energy of the system by a sum of Gaussians centred along the trajectory followed by a suitably chosen set of collective variables (CVs), thereby forcing the system to migrate from one minimum to the next. The power of metadynamics is demonstrated by the large number of extensions and variants that have been developed. The first scope of this Technical Review is to present a critical comparison of these variants, discussing their advantages and disadvantages. The effectiveness of metadynamics, and that of the numerous alternative methods, is strongly influenced by the choice of the CVs. If an important variable is neglected, the resulting estimate of the free energy is unreliable, and predicted transition mechanisms may be qualitatively wrong. The second scope of this Technical Review is to discuss how the CVs should be selected, how to verify whether the chosen CVs are sufficient or redundant, and how to iteratively improve the CVs using machine learning approaches

Symmorphosis through dietary regulation: a combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation

Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequeces of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production

Development and evaluation of an emulsion containing lycopene for combating acceleration of skin aging

Licopeno é um carotenóide com potente atividade antioxidante encontrado em grande quantidade no tomate e usado no combate a diversas doenças como doenças cardiovasculares e diferentes tipos de cânceres, incluindo o câncer de próstata. O objetivo desse trabalho foi desenvolver uma emulsão contendo extrato de licopeno obtido do tomate salada e avaliar a citotoxicidade do extrato, a estabilidade, o comportamento reológico, atividade antioxidante e permeação do fitocosmético. O cosmético foi desenvolvido utilizando fase oleosa contendo derivados de Karité e submetido à avaliação da estabilidade físico-química, espalhabilidade, análise térmica, comportamento reológico, qualidade microbiológica, citotoxicidade, atividade antioxidante e testes de permeação e retenção cutânea. Os resultados demonstraram que o fitocosmético é estável, apresenta comportamento reológico desejável para uma formulação tópica e é um produto promissor para ser utilizado no combate à aceleração do envelhecimento cutâneo.Lycopene, a carotenoid and potent antioxidant is found in large quantities in tomatoes. Lycopene combats diseases, such as cardiovascular disease and different types of cancer, including prostate cancer. However, its topical use in emulsion form for the combat of skin aging is under-explored. The aim of the present study was to develop an emulsion containing lycopene extracted from salad tomatoes and evaluate its cytotoxicity, stability, rheological behavior, antioxidant activity and phytocosmetic permeation. The developed cosmetic comprised an oil phase made up of shea derivatives and was evaluated in terms of its physiochemical stability, spreadability, thermal analysis, rheological behavior, microbiological quality, cytotoxicity, antioxidant activity, cutaneous permeation and retention. The results demonstrate that this phytocosmetic is stable, exhibits satisfactory rheological behavior for a topical formula and is a promising product for combating skin aging

Metabolic constituents of grapevine and grape-derived products

The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology

Targeting tumor-associated macrophages by anti-tumor Chinese materia medica

Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy