Hybrid Materials Obtained by Immobilization of Biosynthesized Ag Nanoparticles with Antioxidant and Antimicrobial Activity.

Ag nanoparticles (AgNPs) were biosynthesized using sage (Salvia officinalis L.) extract. The obtained nanoparticles were supported on SBA-15 mesoporous silica (S), before and after immobilization of 10% TiO2 (Degussa-P25, STp; commercial rutile, STr; and silica synthesized from Ti butoxide, STb). The formation of AgNPs was confirmed by X-ray diffraction. The plasmon resonance effect, evidenced by UV-Vis spectra, was preserved after immobilization only for the sample supported on STb. The immobilization and dispersion properties of AgNPs on supports were evidenced by TEM microscopy, energy-dispersive X-rays, dynamic light scattering, photoluminescence and FT-IR spectroscopy. The antioxidant activity of the supported samples significantly exceeded that of the sage extract or AgNPs. Antimicrobial tests were carried out, in conditions of darkness and white light, on Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. Higher antimicrobial activity was evident for SAg and STbAg samples. White light increased antibacterial activity in the case of Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). In the first case, antibacterial activity increased for both supported and unsupported AgNPs, while in the second one, the activity increased only for SAg and STbAg samples. The proposed antibacterial mechanism shows the effect of AgNPs and Ag+ ions on bacteria in dark and light conditions.

Evaluating the Antioxidant and Antidiabetic Properties of Medicago sativa and Solidago virgaurea Polyphenolic-Rich Extracts.

The present study evaluated the antioxidant and antidiabetic properties of Medicago sativa and Solidago virgaurea extracts enriched in polyphenolic compounds. The extracts were obtained by accelerated solvent extraction (ASE) and laser irradiation. Then, microfiltration was used for purification, followed by nanofiltration used to concentrate the two extracts. The obtained extracts were analyzed to determine their antioxidant activity using DPPH radical scavenging and reducing power methods. The antidiabetic properties have been investigated in vitro on a murine insulinoma cell line (ß-TC-6) by the inhibition of α-amylase and α-glucosidase. M. sativa obtained by laser irradiation and concentrated by nanofiltration showed the highest DPPH• scavenging (EC50 = 105.2 ± 1.1 µg/mL) and reducing power activities (EC50 = 40.98 ± 0.2 µg/mL). M. sativa extracts had higher inhibition on α-amylase (IC50 = 23.9 ± 1.2 µg/mL for concentrated extract obtained after ASE, and 26.8 ± 1.1), while S. virgaurea had the highest α-glucosidase inhibition (9.3 ± 0.9 µg/mL for concentrated extract obtained after ASE, and 8.6 ± 0.7 µg/mL for concentrated extract obtained after laser extraction). The obtained results after evaluating in vitro the antidiabetic activity showed that the treatment with M. sativa and S. virgaurea polyphenolic-rich extracts stimulated the insulin secretion of ß-TC-6 cells, both under normal conditions and under hyperglycemic conditions as well. This paper argues that M. sativa and S. virgaurea polyphenolic-rich extracts could be excellent natural sources with promising antidiabetic potential.

In Vitro Assessment of the Antidiabetic and Anti-Inflammatory Potential of Artemisia absinthium, Artemisia vulgaris and Trigonella foenum-graecum Extracts Processed Using Membrane Technologies.

Recently, there has been increased interest in the discovery of new natural herbal remedies for treating diabetes and inflammatory diseases. In this context, this work analyzed the antidiabetic and anti-inflammatory potential of Artemisia absinthium, Artemisia vulgaris and Trigonella foenum-graecum herbs, which have been studied less from this point of view. Therefore, extracts were prepared and processed using membrane technologies, micro- and ultrafiltration, to concentrate the biologically active principles. The polyphenol and flavone contents in the extracts were analyzed. The qualitative analysis of the polyphenolic compounds was performed via HPLC, identifying chlorogenic acid, rosmarinic acid and rutin in A. absinthium; chlorogenic acid, luteolin and rutin in A. vulgaris; and genistin in T. foenum-graecum. The antidiabetic activity of the extracts was analyzed by testing their ability to inhibit α-amylase and α-glucosidase, and the anti-inflammatory activity was analyzed by testing their ability to inhibit hyaluronidase and lipoxygenase. Thus, the concentrated extracts of T. foenum-graecum showed high inhibitory activity on a-amylase-IC50 = 3.22 ± 0.3 µg/mL-(compared with acarbose-IC50 = 3.5 ± 0.18 µg/mL) and high inhibitory activity on LOX-IC50 = 19.69 ± 0.52 µg/mL (compared with all standards used). The concentrated extract of A. vulgaris showed increased α-amylase inhibition activity-IC50 = 8.57 ± 2.31 µg/mL-compared to acarbose IC50 = 3.5 ± 0.18 µg/mL. The concentrated extract of A. absinthium showed pronounced LOX inhibition activity-IC50 = 19.71 ± 0.79 µg/mL-compared to ibuprofen-IC50 = 20.19 ± 1.25 µg/mL.

Changes in pNFH Levels in Cerebrospinal Fluid and Motor Evolution after the Loading Dose with Nusinersen in Different Types of Spinal Muscular Atrophy.

Aim and Objectives: The objective of our retrospective study was to investigate the changes in pNFH levels in cerebrospinal fluid, which is a reliable marker of neuronal damage, after the loading dose of nusinersen in different types of spinal muscular atrophy. Materials and Methods: We analyzed the spinal muscular atrophy types, the number of copies of the SMN2 gene, and the progression of the motor status using specific motor function scales in a group of 38 patients with spinal muscular atrophy types 1, 2, and 3. Results: We found a significant inverse correlation between pNFH levels and patient age, progress on functional motor scales, and nusinersen administration. Our results also revealed that the neurofilament levels in the cerebrospinal fluid were higher in patients with 2 SMN2 copies than those with more than 2 copies, although the association was not statistically significant due to the abnormal distribution of the values. Conclusions: We identified several predictors of favorable evolution under nusinersen treatment, including spinal muscular atrophy type 1, children aged ≤ 30 months, and the presence of only 2 copies of SMN2. Our study provides important insights into the use of pNFH as a biomarker to monitor disease progression and responses to treatment in patients with spinal muscular atrophy.

Artemisia abrotanum and Symphytum officinale Polyphenolic Compounds-Rich Extracts with Potential Application in Diabetes Management.

Lately, there has been increased interest in the development of phytochemical alternatives for the prevention and treatment of type 2 diabetes, the alternatives that are able to reduce or prevent glucose absorption by inhibiting digestive enzymes. In this context, this study aims to analyze the inhibitory α-amylase and α-glucosidase activities of Artemisia abrotanum and Symphytum officinale polyphenolic compound-rich extracts obtained by membrane technologies (micro- and ultrafiltration). Polyphenols and flavones content, HPLC-MS polyphenolic compounds profiling, antioxidant activity, and cytotoxic potential of these herbs were determined. Major phenolic acid compounds were chlorogenic acid, ellagic acid, caffeic acid, and rosmarinic acid. The flavone content was higher in the case of A. abrotanum extracts, and the major compounds were rutin and umbelliferone. The polyphenolic-rich extract of A. abrotanum had the highest quantities of polyphenols, 977.75 µg/mL, and flavones, 552.85 µg/mL, as well as a pronounced α-amylase inhibitory activity (IC50 1881.21 ± 1.8 mg/mL), a value close to acarbose inhibitory activity (IC50 1110.25 ± 8.82 mg/mL) that was used as the control for both enzymes. The α-glucosidase inhibitory activity was higher for both herb extracts, more pronounced for S. officinale polyphenolic-rich extract (IC50 291.56 ± 2.1 mg/mL), a value higher than that of acarbose (IC50 372.35 ± 3.2 mg/mL). These plants show potential as a complementary therapy for type 2 diabetes management.

New Hybrid Nanofiltration Membranes with Enhanced Flux and Separation Performances Based on Polyphenylene Ether-Ether-Sulfone/Polyacrylonitrile/SBA-15.

This study presents the preparation of hybrid nanofiltration membranes based on poly(1,4-phenylene ether ether sulfone), polyacrylonitrile, poly(vinyl pyrrolidone), and SBA-15 mesoporous silica. Laser treatment of polymeric solutions to enhance the hydrophilicity and performance of membranes was investigated. The membranes' structure was characterized using scanning electron (SEM) and atomic force (AFM) microscopy and contact angle measurements. The addition of PAN in the casting solution produced significant changes in the membrane structure, from finger-like porous structures to sponge-like porous structures. Increased PAN concentration in the membrane composition enhanced the hydrophilicity of the membrane surface, which also accounted for the improvement in the antifouling capabilities. The permeation of apple pomace extract and the content of polyphenols and flavonoids were used to evaluate the efficacy of the hybrid membranes created. The results showed that the hybrid nanofiltration membranes based on PPEES/PAN/PVP/SBA-15: 15/5/1/1 and 17/3/1/1 exposed to laser for 5 min present a higher rejection coefficient to total polyphenols (78.6 ± 0.7% and 97.8 ± 0.9%, respectively) and flavonoids (28.7 ± 0.2% and 50.3 ± 0.4%, respectively) and are substantially better than a commercial membrane with MWCO 1000 Da or PPEES-PVP-based membrane.

Nanofiltration Composite Membranes Based on KIT-6 and Functionalized KIT-6 Nanoparticles in a Polymeric Matrix with Enhanced Performances.

The nanofiltration composite membranes were obtained by incorporation of KIT-6 ordered mesoporous silica, before and after its functionalization with amine groups, into polyphenylene-ether-ether-sulfone (PPEES) matrix. The incorporation of silica nanoparticles into PPEES polymer matrix was evidenced by FTIR and UV-VIS spectroscopy. SEM images of the membranes cross-section and their surface topology, evidenced by AFM, showed a low effect of KIT-6 silica nanoparticles loading and functionalization. The performances of the obtained membranes were appraised in permeation of Chaenomeles japonica fruit extracts and the selective separation of phenolic acids and flavonoids. The obtained results proved that the PPEES with functionalized KIT-6 nanofiltration membrane, we have prepared, is suitable for the polyphenolic compound's concentration from the natural extracts.

In Vitro Evaluation of Antidiabetic and Anti-Inflammatory Activities of Polyphenolic-Rich Extracts from Anchusa officinalis and Melilotus officinalis.

This study was focused on the phytochemical composition and biological activities of Anchusa officinalis and Melilotus officinalis polyphenolic-rich extracts obtained by nanofiltration. The high-performance liquid chromatography-mass spectrometry analysis showed that chlorogenic acid and rosmarinic acid were the main phenolic acids in both extracts. The main flavonoid compound from A. officinalis extracts is luteolin, whereas rutin and isoquercitrin are the main flavonoids in M. officinalis. M. officinalis polyphenolic-rich extract had the highest α-amylase (from hog pancreas) inhibitory activity (IC50 = 1.30 ± 0.06 µg/mL) and α-glucosidase (from Saccharomyces cerevisiae) inhibitory activity (IC50 = 92.18 ± 1.92 µg/mL). However, both extracts presented a significant α-glucosidase inhibitory activity. Furthermore, the hyaluronidase inhibition of polyphenolic-rich extracts also proved to be stronger (IC50 = 11.8 ± 0.1 µg/mL for M. officinalis and 36.5 ± 0.2 µg/mL for A. officinalis), but there was moderate or low lipoxygenase inhibition. The studies on the fibroblast cell line demonstrated that both A. officinalis and M. officinalis polyphenolic-rich extracts possess the cytotoxic effect at a concentration higher than 500 µg/mL. The experimental data suggest that both extracts are promising candidates for the development of natural antidiabetic and anti-inflammatory food supplements.

Chemical and Bioactivity Evaluation of Eryngium planum and Cnicus benedictus Polyphenolic-Rich Extracts.

This study evaluated the biological activities of Eryngium planum and of Cnicus benedictus extracts enriched in polyphenols obtained by nanofiltration. The HPLC-MS analysis showed that E. planum contains mainly flavonoids, especially rutin, while in C. benedictus extracts show the high concentration of the phenolic acids, principally the chlorogenic acid and sinapic acid. Herein, there is the first report of ursolic acid, genistin, and isorhamnetin in E. planum and C. benedictus. C. benedictus polyphenolic-rich extract showed high scavenging activity (IC50=0.0081 mg/mL) comparable to that of standard compound (ascorbic acid) and a higher reducing power (IC50= 0.082 mg/mL), with IC50 having a significantly lower value than IC50 for ascorbic acid. Both extracts were nontoxic to NCTC cell line. Among the investigated herbs, E. planum polyphenolic-rich extract showed the highest inhibitory activities with the IC50 value of 31.3 µg/mL for lipoxygenase and 24.6 µg/mL for hyaluronidase. Both polyphenolic-rich extracts had a higher inhibitory effect on α-amylase and α-glucosidase than that of the acarbose. The synergistic effect of ursolic acid, rutin, chlorogenic acid, rosmarinic acid, genistin, and daidzein identified in polyphenolic-rich extracts could be mainly responsible for the pharmacological potentials of the studied extracts used in managing inflammation and diabetes.

Antioxidant activity, acetylcholinesterase and tyrosinase inhibitory potential of Pulmonaria officinalis and Centarium umbellatum extracts.

In this study several investigations and tests were performed to determine the antioxidant activity and the acetylcholinesterase and tyrosinase inhibitory potential of Pulmonaria officinalis and Centarium umbellatum aqueous extracts (10% mass) and ethanolic extracts (10% mass and 70% ethanol), respectively. Moreover, for each type of the prepared extracts of P. officinalis and of C. umbellatum the content in the biologically active compounds - polyphenols, flavones and proanthocyanidins was determined. The antioxidant activity was assessed using two methods, namely the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and reducing power assay. The analyzed plant extracts showed a high acetylcholinesterase and tyrosinase inhibitory activity in the range of 72.24-94.24% (at the highest used dose - 3 mg/mL), 66.96% and 94.03% (at 3 mg/mL), respectively correlated with a high DPPH radical inhibition - 70.29-84.9% (at 3 mg/mL). These medicinal plants could provide a potential natural source of bioactive compounds and could be beneficial to the human health, especially in the neurodegenerative disorders and as sources of natural antioxidants in food industry.

Anti-inflammatory and antioxidant activities of the Impatiens noli-tangere and Stachys officinalis polyphenolic-rich extracts

ABSTRACT This study evaluated the anti-inflammatory and antioxidant activities of Impatiens noli-tangere L., Balsaminaceae, and of Stachys officinalis L., Lamiaceae, polyphenolic-rich extracts obtained by nanofiltration process. Results showed the great potential and efficiency of the nanofiltration process to concentrate the herbal extract's main polyphenolic compounds (over 91% phenolic acids and flavonoids retention). S. officinalis polyphenolic-rich extracts had high antioxidant activities (IC50 2.5 µg/ml) compared to I. noli-tangere polyphenolic-rich extracts (IC50 19.3 µg/ml) and similar with that of ascorbic acid. Polyphenolic-rich extracts were investigated to determine the pro-inflammatory enzymes lipoxygenase, cyclooxygenase-1 and cyclooxygenase-2 and their inhibitory activity. Furthermore, high inhibitory activity of the examined extracts was reported for the first time, for both lipoxygenase (IC50 2.46 and 1.22 µg/ml for I. noli-tangere and S. officinalis polyphenolic-rich extracts, respectively), cyclooxygenase-1 (IC50 18.4 and 10.1 µg/ml for I. noli-tangere and S. officinalis polyphenolic-rich extracts, respectively) and cyclooxygenase-2 (IC50 = 1.9 and 1.2 mg/ml for I. noli-tangere and S. officinalis polyphenolic-rich extracts, respectively). Additionally, the in vivo studies showed that S. officinalis polyphenolic-rich extract has a higher anti-inflammatory effect, the hind-paw volume employed for both models determined that I. noli-tangere polyphenolic-rich extract and is also higher than that of diclofenac. It was noticed that their anti-inflammatory effect persists for more than 24 h. The I. noli-tangere and S. officinalis polyphenolic-rich extracts exert anti-inflammatory and antioxidant activities and these properties can be at least partly assigned to the presence of ursolic acid, caffeic acid, rosmarinic acid, quercetin and also anthocyanidins (genistin). The obtained results indicate the anti-inflammatory potential of the studied herbal extracts.

Clinical Outcomes in Duchenne Muscular Dystrophy: A Study of 5345 Patients from the TREAT-NMD DMD Global Database.

BACKGROUND: Recent short-term clinical trials in patients with Duchenne Muscular Dystrophy (DMD) have indicated greater disease variability in terms of progression than expected. In addition, as average life-expectancy increases, reliable data is required on clinical progression in the older DMD population. OBJECTIVE: To determine the effects of corticosteroids on major clinical outcomes of DMD in a large multinational cohort of genetically confirmed DMD patients. METHODS: In this cross-sectional study we analysed clinical data from 5345 genetically confirmed DMD patients from 31 countries held within the TREAT-NMD global DMD database. For analysis patients were categorised by corticosteroid background and further stratified by age. RESULTS: Loss of ambulation in non-steroid treated patients was 10 years and in corticosteroid treated patients 13 years old (p = 0.0001). Corticosteroid treated patients were less likely to need scoliosis surgery (p < 0.001) or ventilatory support (p < 0.001) and there was a mild cardioprotective effect of corticosteroids in the patient population aged 20 years and older (p = 0.0035). Patients with a single deletion of exon 45 showed an increased survival in contrast to other single exon deletions. CONCLUSIONS: This study provides data on clinical outcomes of DMD across many healthcare settings and including a sizeable cohort of older patients. Our data confirm the benefits of corticosteroid treatment on ambulation, need for scoliosis surgery, ventilation and, to a lesser extent, cardiomyopathy. This study underlines the importance of data collection via patient registries and the critical role of multi-centre collaboration in the rare disease field.

Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy.

Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy, is the most common form of epilepsy and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan nuclear receptor (RORß), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5-10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures.

Probiotic Strains Influence on Infant Microbiota in the In Vitro Colonic Fermentation Model GIS1.

The main goal of our study was to evaluate the effect of the individual administration of five lyophilized lactic acid bacteria strains (Lactobacillus fermentum 428ST, Lactobacillus rhamnosus E4.2, Lactobacillus plantarum FCA3, Lactobacillus sp. 34.1, Weissella paramesenteroides FT1a) against the in vitro simulated microbiota of the human colon using the GIS1 system. The influence on the metabolic activity was also assessed by quantitative determination of proteins and polysaccharides at each segment of human colon. The obtained results indicated that the lactic acid bacteria L. rhamnosus E4.2 and W. paramesenteroides FTa1 had better efficiency in synthesising exopolysaccharides and also a better probiotic potential and therefore could be recommended for use in probiotics products or food industry.

Inhibitory potential of some Romanian medicinal plants against enzymes linked to neurodegenerative diseases and their antioxidant activity.

CONTEXT: Eryngium planum, Geum urbanum and Cnicus benedictus plants are an endemic botanical from the Romanian used in folk medicine. OBJECTIVE: The extracts from three Romanian medicinal plants were investigated for their possible neuroprotective potential. MATERIALS AND METHODS: Within this study, in vitro neuroprotective activity of the extracts of E. planum, G. urbanum, and C. benedictus plants were investigated via inhibition of acetylcholinesterase (AChE) and tyrosinase (TYR). Total content of phenolics, flavonoids, and proanthocyanidins, high-performance liquid chromatography profile of the main phenolic compounds and antioxidant activity were also determined. RESULTS: Among the tested extracts, the best inhibition of AChE (88.76 ± 5.2%) and TYR (88.5 ± 5.2%) was caused by C. benedictus ethanol (EtOH) extract. The G. urbanum extracts exerted remarkable scavenging effect against 2, 2-diphenyl-1-picrylhydrazyl (IC50, 7.8 ± 0.5 µg/mL aqueous extract, and IC50, 1.3 ± 0.1 µg/mL EtOH extract, respectively) and reducing power, whereas the EtOH extract of C. benedictus showed high scavenging activity (IC50, 0.609 ± 0.04 mg/mL), also. CONCLUSION: According to our knowledge, this is the first study that demonstrates in vitro neuroprotective effects of E. planum, G. urbanum and C. benedictus.

The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations.

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

New type of chitosan/2-hydroxypropyl-ß-cyclodextrin composite membrane for gallic acid encapsulation and controlled release.

A new type of chitosan/2-hydroxypropyl-ß-cyclodextrin composite membrane have been developed for the encapsulation and controlled release of gallic acid. The morphology of the composite membrane was investigated by infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM), whereas swelling gallic acid and release properties were investigated by UV-visible spectroscopy. The release behavior with pH changes was also explored. The composite membrane based on chitosan/2-hydroxypropyl-ß-cyclodextrin with gallic acid included showed improved antioxidant capacities compared to plain chitosan membrane. The information obtained in this study will facilitate the design and preparation of composite membrane based on chitosan and could open a wide range of applications, particularly its use as an antioxidant in food, food packaging, biomedical (biodegradable soft porous scaffolds for enhance the surrounding tissue regeneration), pharmaceutical and cosmetics industries.

Evaluation of Geranium spp., Helleborus spp. and Hyssopus spp. polyphenolic extracts inhibitory activity against urease and α-chymotrypsin.

This study was meant to determine the inhibitory activity of tannins and flavonoid compounds from Geranium robertianum, Helleborus purpurascens and Hyssopus officinale plant polyphenol rich extracts against urease and α-chymotrypsin. The G. robertianum, H. purpurascens and H. officinale extracts were purified and concentrated by microfiltration and ultrafiltration. Phenolic compounds including flavonoids and tannins have been linked to many pharmacological activities. Thus, the polyphenolic content of the extracts was assessed by UV-Vis spectroscopy and HPLC. The concentrated extracts enriched in polyphenolic compounds (flavonoids, tannins and phenolic acids) showed a significant inhibition against urease from jack bean (over 90%), whereas in case of the α-chymotrypsin, they proved to have an inhibition below 54%. The results of this support the use of G. robertianum, H. purpurascens and H. officinale polyphenolic extracts as potential sources of urease inhibitors. Among the three plant extracts tested, H. officinale polyphenolic extracts exhibited a high inhibitory activity (92.67%) against urease and low inhibition (19.6%) against α-chymotrypsin and could be considered as possible remedy in ulcer treatment.

The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence <5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry.

Analysis of molecular determinants of PRL-3.

In order to analyse whether a C-terminal polybasic sequence represents a nuclear localization signal (NLS) we obtained several truncated and mutant forms of protein of regerating liver (PRL)-3 and evaluated their subcellular localization as compared to the wild-type form. Our results invalidate the hypothesis that this is an NLS. We also analysed the influence of the C- and N-terminal residues on the phosphatase activity of PRL-3. Our results provide in vitro evidence that the C-terminal CAAX motif, besides directing the protein farnesylation, plays an additional regulatory role by inhibiting the catalytic efficiency of PRL-3. Taking into account the results we obtained, as well as reported data, we propose a hypothetical molecular mechanism for the nucleocytoplasmic localization and transfer of PRL-3.