High-order harmonic generation by static coherent states method in single-electron atomic and molecular systems

We solve the time-dependent Schrodinger equation using the coherent states as basis sets for computing high harmonic generation (HHG) in a full-dimensional single-electron "realistic" system. We apply the static coherent states (SCS) method to investigate HHG in the hydrogen molecular ion induced by a linearly polarized laser field. We show that SCS gives reasonable agreement compared to the three dimensional unitary split-operator approach. Next, we study isolated attosecond pulse generation in H2+. To do so, we employ the well-known polarization gating technique, which combines two delayed counter-rotating circular laser pulses, and opens up a gate at the central portion of the superposed pulse. Our results suggest that the SCS method can be used for full-dimensional quantum simulation of higher dimensional systems such as the hydrogen molecule in the presence of an external laser field

Mecanismes d'acció dels antifúngics i resistència en llevats

Si bé s'ha avançat en la síntesi de nous antifúngics i se'n coneix el mode d'acció, els mecanismes moleculars de resistència encara són insuficientment coneguts, i afecten principalment els llevats i els azoles. El fluconazole ha estat un dels antifúngics en els quals més s'ha aprofundit l'estudi de les resistències, i s'ha comprovat que aquestes poden ser degudes a mecanismes múltiples, entre els quals la major activitat dels transportadors o bombes d'efflux tenen un paper important, ja que expulsen a l'exterior l'antifúngic que ha penetrat a la cèl·lula. Les alteracions de la diana cèl·lular i l'alteració de la via de síntesi de l'ergosterol present a la membrana també tenen un paper important. Els gens CDR1 i BEN-R estan implicats en aquests mecanismes de resistència. En altres antifúngics com l'amfotericina B i les equinocandines les resistències no semblen ser problemes clínics importants. Candida albicans pot presentar resistències secundàries a la 5- fluorocitosina per pèrdua d'activitat enzimàtica i disminució de l'efecte del metabòlit actiu. La relació entre resistències i manca de resposta terapèutica ha estat demostrada en models animals i estudis clínics, tot i que la resposta al tractament antifúngic depèn en molts casos d'altres factors com l'estat immunitari del malalt, l'espècie fúngica causal, la farmacocinètica i la biodisponibilitat del fàrmac, entre d'altres.Most of our knowledge on antifungal resistance mechanisms is related to yeasts and azoles. Fluconazole is the most studied antifungal and several resistance mechanisms have been demonstrated. Efflux pump seems to be the most important, but cell-target changes and modifi- cations in the ergosterol metabolic way are also relevant. CDR1 and BEN-R are two genes involved in those resistance mechanisms. Resistance is not a major clinical problem with amphotericin B and echinocandins, but Candida albicans can have secondary resistances to 5-fluorocitosyne when enzymatic activity is lost and the active metabolite is lacking. Relationship among antifungal resistance and therapeutic response has been shown in experimental animal models and in clinical studies, but response to the treatment is also related to immunological status of the patient as well to the fungal species, and pharmacological aspects of the drug

Delirium in Hospitalized Elderly Patients and Post-Discharge Mortality

OBJECTIVE: To determine the impact of delirium on post-discharge mortality in hospitalized older patients. INTRODUCTION: Delirium is frequent in hospitalized older patients and correlates with high hospital mortality. There are only a few studies about its impact on post-discharge mortality. METHODS: This is a prospective study of patients over 60 years old who were hospitalized in the Geriatric Unit at Hospital das Clínicas of São Paulo between May 2006 and March 2007. Upon admission, demographics, comorbidities, number of drugs taken, and serum albumin concentration were evaluated for each patient. Delirium was diagnosed according to the DSM-IV criteria. Patients were divided into group A (with delirium) and group B (without delirium). One year after discharge, the patients or their caregivers were contacted to assess days of survival. RESULTS: The sample included 199 patients, 66 (33%) of whom developed delirium (Group A). After one year, 33 (50%) group A patients had died, and 45 (33.8%) group B patients had died (p = 0.03). There was a significant statistical difference in average age (p = 0.001) and immobility (p <0.001) between groups A and B. There were no statistically significant differences between groups A and B in number of drugs taken greater than four (p = 0.62), sex (p = 0.54) and number of diagnoses greater than four (p = 0.21). According to a multivariate analysis, delirium was not an independent predictor of post-discharge mortality. The predictors of post-discharge mortality were age > 80 years (p = 0.029), albumin concentration < 3.5 g/dl (p = 0.001) and immobility (p = 0.007). CONCLUSION: Delirium is associated with higher post-discharge mortality as a dependent predictor

Neuronal differentiation of rat hair follicle stem cells: The involvement of the neuroprotective factor seladin-1 (DHCR24)

Background: The seladin-1 (selective Alzheimer disease indicator-1), also known as DHCR24, is a gene found to be down-regulated in brain region affected by Alzheimer disease (AD). Whereas, hair follicle stem cells (HFSC), which are affected in with neurogenic potential, it might to hypothesize that this multipotent cell compartment is the predominant source of seladin-1. Our aim was to evaluate seladin-1 gene expression in hair follicle stem cells. Methods: In this study, bulge area of male Wistar rat HFSC were cultured and then characterized with Seladin-1 immunocytochemistry and flow cytometry on days 8 to 14. Next, 9-11-day cells were evaluated for seladin-1 gene expression by real-time PCR. Results: Our results indicated that expression of the seladin-1 gene (DHCR24) on days 9, 10, and 11 may contribute to the development of HFSC. However, the expression of this gene on day 11 was more than day 10 and on 10th day was more than day 9. Also, we assessed HFSC on day 14 and demonstrated these cells were positive for β-III tubulin, and seladin-1 was not expressed in this day. Conclusion: HFSC express seladin-1 and this result demonstrates that these cells might be used to cell therapy for AD in future

Stimulatory Effects of Lycium shawii on Human Melanocyte Proliferation, Migration, and Melanogenesis: In Vitro and In Silico Studies

There is no first-line treatment for vitiligo, a skin disease characterized by a lack of melanin produced by the melanocytes, resulting in an urgent demand for new therapeutic drugs capable of stimulating melanocyte functions, including melanogenesis. In this study, traditional medicinal plant extracts were tested for cultured human melanocyte proliferation, migration, and melanogenesis using MTT, scratch wound-healing assays, transmission electron microscopy, immunofluorescence staining, and Western blot technology. Of the methanolic extracts, Lycium shawii L. (L. shawii) extract increased melanocyte proliferation at low concentrations and modulated melanocyte migration. At the lowest tested concentration (i.e., 7.8 μg/mL), the L. shawii methanolic extract promoted melanosome formation, maturation, and enhanced melanin production, which was associated with the upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2 melanogenesis-related proteins, and melanogenesis-related proteins. After the chemical analysis and L. shawii extract-derived metabolite identification, the in silico studies revealed the molecular interactions between Metabolite 5, identified as apigenin (4,5,6-trihydroxyflavone), and the copper active site of tyrosinase, predicting enhanced tyrosinase activity and subsequent melanin formation. In conclusion, L. shawii methanolic extract stimulates melanocyte functions, including melanin production, and its derivative Metabolite 5 enhances tyrosinase activity, suggesting further investigation of the L. shawii extract-derived Metabolite 5 as a potential natural drug for vitiligo treatment

The effects of probiotic supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson�s disease: A randomized, double-blind, placebo-controlled trial

Background: This study was conducted to evaluate the effects of probiotic supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson�s disease (PD).Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted in 50 patients with PD as a pilot study. Participants were randomly allocated into two groups to take either 8�109 CFU/day probiotic supplements or placebo (n = 25 each group, one capsule daily) for 12 weeks. Gene expression related to inflammation, insulin, and lipid was quantified in peripheral blood mononuclear cells (PBMC) of PD patients, with RT-PCR method. Results: After the 12-week intervention, compared with the placebo, probiotic intake downregulated gene expression of interleukin-1 (IL-1) (P = 0.03), IL-8 (P < 0.001) and tumor necrosis factor alpha (TNF-α) (P=0.04) in PBMC of subjects with PD. In addition, probiotic supplementation upregulated transforming growth factor beta (TGF-β) (P = 0.02) and peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of probiotic intake on gene expression of low-density lipoprotein receptor (LDLR) and vascular endothelial growth factor (VEGF) in PBMC of patients with PD. Conclusion: Overall, probiotics supplementation for 12 weeks in PD patients significantly improved gene expression of IL-1, IL-8, TNF-α, TGF-β and PPAR-γ, but did not affect gene expression of VEGF and LDLR, and biomarkers of inflammation and oxidative stress. © 2018 The Author(s)

An overview of anti-diabetic plants used in Gabon: Pharmacology and Toxicology

© 2017 Elsevier B.V. All rights reserved.Ethnopharmacological relevance: The management of diabetes mellitus management in African communities, especially in Gabon, is not well established as more than 60% of population rely on traditional treatments as primary healthcare. The aim of this review was to collect and present the scientific evidence for the use of medicinal plants that are in currect by Gabonese traditional healers to manage diabetes or hyperglycaemia based here on the pharmacological and toxicological profiles of plants with anti-diabetic activity. There are presented in order to promote their therapeutic value, ensure a safer use by population and provide some bases for further study on high potential plants reviewed. Materials and methods: Ethnobotanical studies were sourced using databases such as Online Wiley library, Pubmed, Google Scholar, PROTA, books and unpublished data including Ph.D. and Master thesis, African and Asian journals. Keywords including ‘Diabetes’ ‘Gabon’ ‘Toxicity’ ‘Constituents’ ‘hyperglycaemia’ were used. Results: A total of 69 plants currently used in Gabon with potential anti-diabetic activity have been identified in the literature, all of which have been used in in vivo or in vitro studies. Most of the plants have been studied in human or animal models for their ability to reduce blood glucose, stimulate insulin secretion or inhibit carbohydrates enzymes. Active substances have been identified in 12 out of 69 plants outlined in this review, these include Allium cepa and Tabernanthe iboga. Only eight plants have their active substances tested for anti-diabetic activity and are suitables for further investigation. Toxicological data is scarce and is dose-related to the functional parameters of major organs such as kidney and liver. Conclusion: An in-depth understanding on the pharmacology and toxicology of Gabonese anti-diabetic plants is lacking yet there is a great scope for new treatments. With further research, the use of Gabonese anti-diabetic plants is important to ensure the safety of the diabetic patients in Gabon.Peer reviewedFinal Accepted Versio

Stimulatory effects of Lycium shawii on human melanocyte proliferation, migration, and melanogenesis: In vitro and in silico studies

There is no first-line treatment for vitiligo, a skin disease characterized by a lack of melanin produced by the melanocytes, resulting in an urgent demand for new therapeutic drugs capable of stimulating melanocyte functions, including melanogenesis. In this study, traditional medicinal plant extracts were tested for cultured human melanocyte proliferation, migration, and melanogenesis using MTT, scratch wound-healing assays, transmission electron microscopy, immunofluorescence staining, and Western blot technology. Of the methanolic extracts, Lycium shawii L. (L. shawii) extract increased melanocyte proliferation at low concentrations and modulated melanocyte migration. At the lowest tested concentration (i.e., 7.8 μg/mL), the L. shawii methanolic extract promoted melanosome formation, maturation, and enhanced melanin production, which was associated with the upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2 melanogenesis-related proteins, and melanogenesis-related proteins. After the chemical analysis and L. shawii extract-derived metabolite identification, the in silico studies revealed the molecular interactions between Metabolite 5, identified as apigenin (4,5,6-trihydroxyflavone), and the copper active site of tyrosinase, predicting enhanced tyrosinase activity and subsequent melanin formation. In conclusion, L. shawii methanolic extract stimulates melanocyte functions, including melanin production, and its derivative Metabolite 5 enhances tyrosinase activity, suggesting further investigation of the L. shawii extract-derived Metabolite 5 as a potential natural drug for vitiligo treatment

Induction of protein citrullination and auto-antibodies production in murine exposed to nickel

Abstract Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can trigger protein citrullination, which might constitute a common pathogenic link to disease development. Here we demonstrated auto-antibody production in serum of nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples. The observed systemic responses in mice exposed to nanomaterials support the evidence linking exposure to environmental factors with the development of autoimmunity responses and reinforces the need for comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials induce pathological processes that mimic those observed in Pleural MM, and therefore require further investigations into their carcinogenicity