Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin

The history of using vesicular systems for drug delivery to and through skin started nearly three decades ago with a study utilizing phospholipid liposomes to improve skin deposition and reduce systemic effects of triamcinolone acetonide. Subsequently, many researchers evaluated liposomes with respect to skin delivery, with the majority of them recording localized effects and relatively few studies showing transdermal delivery effects. Shortly after this, Transfersomes were developed with claims about their ability to deliver their payload into and through the skin with efficiencies similar to subcutaneous administration. Since these vesicles are ultradeformable, they were thought to penetrate intact skin deep enough to reach the systemic circulation. Their mechanisms of action remain controversial with diverse processes being reported. Parallel to this development, other classes of vesicles were produced with ethanol being included into the vesicles to provide flexibility (as in ethosomes) and vesicles were constructed from surfactants and cholesterol (as in niosomes). Thee ultradeformable vesicles showed variable efficiency in delivering low molecular weight and macromolecular drugs. This article will critically evaluate vesicular systems for dermal and transdermal delivery of drugs considering both their efficacy and potential mechanisms of action

Fatty acid profiles of the main lipid classes of green seaweeds from fish pond aquaculture

The lipid composition of five species of green seaweeds (Chaetomorpha linum, Rhizoclonium riparium, Ulva intestinalis, Ulva lactuca, and Ulva prolifera) grown in fish pond aquaculture systems was studied. In particular, the overall fatty acid (FA) profile and the FA profile of each main lipid class found in these seaweed species were thoroughly analyzed. It was found that every seaweed had a specific FA profile, whose specificities were rendered more obvious with the study of the FA profile per lipid class. However, between U.lactuca and U.intestinalis, there were only minor differences. Nonetheless, it was possible to identify significant differences between the palmitic acid content in the phospholipid (PL) and glycolipid (GL) classes of each seaweed. A clear distinction between the FA profiles of R.riparium and C.linum, which belong to the Cladophorales order, and those of Ulva genus, Ulvales order, was also determined. Moreover, there were also differences among lipid classes, yielding large contrasts between PLs+GLs and triacylglycerols (TAGs) as well as between monoacylglycerols (MAGs) and free fatty acids (FFAs). This study also found evidence supporting the location of particular FAs in specific TAG positions. FA profiles have the potential to be used as a chemotaxonomic tool in green seaweeds, providing a simple method to check authenticity of seaweed used as food.Fundacao para a Ciencia e a Tecnologiainfo:eu-repo/semantics/publishedVersio

New insights in Aicardi-Goutières Syndrome: association between a RNU7-1 variant and novel pathologic mechanisms

Aicardi-Goutières syndrome (AGS) is a rare genetic pediatric disorder currently associated with mu-tations in 9 genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, IFIH1, LSM11 and RNU7-1), all of which encode for proteins or transcripts involved in nucleic acid metabolism and signaling. In this thesis work, a pathologic variant of the RNU7-1 gene (AGS9) was analyzed. This gene encodes for the U7 small nucleolar RNA (U7 snRNA), an essential compo-nent of the U7 snRNP complex. The function of U7 snRNP is to operate the endonucleolytic cleavage of the poly-A tail in replication-dependent histones (RDHs) pre-mRNAs during their maturation process. RDHs genes encode the four core histones and the linker histone family. In AGS, mutations in RNU7-1 have been linked to defects in U7 complex synthesis, resulting in the production of aberrant RDHs isoforms that possess a poly-A tail. In this condition, chromatin is recognized as a foreign genome and acti-vates the innate immune cGAS-STING cascade, leading to increased type I IFN production and induction of transcription of interferon-stimulated genes (ISGs). As RNU7-1 (AGS9) is the least characterized AGS-related gene, the aim of this pro-ject is to dissect its role in AGS pathogenesis. To this end, this work both investigated canonical AGS features such as the potential upregulation of IFNα and ISGs, and spe-cific outcomes of a RNU7-1 pathologic variant in primary dermal fibroblasts obtained from an AGS9 patient and compared to a healthy age- and sex-matched control. Results of this thesis work pointed out an altered RNA morphology of U7 snRNA that leads to affects its subcellular localization in AGS9-derived fibroblasts. Moreover, al-tered expression of two AGS-related genes, (both the isoforms of ADAR1 and RNASEH2B) in fibroblasts carrying the pathologic variant of RNU7-1 was highlighted, confirming the strong cooperation between AGS genes in nucleic acid metabolism. The activation of the interferon signature (IS) in response to the mutation was ob-served, with upregulated ISGs and increased IFN score in fibroblasts and whole blood, reinforcing the connection between the RNU7-1 variant and interferon dysregulation. An anti-inflammatory compound, hydroxychloroquine, was then tested to determine its potential effectiveness in reducing IS and IFNα production. Results proven the de-crease of both ISGs and IFNα in AGS9 cells with also a partial restore of cell viability in AGS9 fibroblasts. As aberrant morphology of U7 snRNA could affect its functioning in U7 snRNP, RIP analysis was performed and a decrease in physical association between U7 snRNA and ZFP100 was reported. RNA-sequencing analysis then confirmed the alteration of multiple pathways related to neuron function and interferon signaling in AGS9 fibroblasts. Moreover, transcrip-tional changes in AGS9 cells were related to chromatin structural components. Spe-cifically, it was highlighted that genes involved in histone post-translational modifica-tions were strongly affected. Aberrant RDH histone processing was also confirmed through Real-Time qPCR, western blot and immunochemistry. Moreover, TEM anal-ysis reported a lack of chromatin in AGS9 nuclei, thus reinforcing RNAseq results. Since TEM analysis also revealed smaller mitochondria and reduced localization of ri-bosomes on ER membranes in AGS9 cells, Mitotracker, Mitosox and Click-iT staining assays were carried out to assess mitochondrial activity, ROS production and nascent protein production, respectively. Results demonstrated a reduced basal mitochondrial activity together with an increase production of ROS, and a reduced nascent protein production in AGS9 fibroblasts. In conclusion, these insights contribute to a more comprehensive characterization of AGS, shedding light on potential therapeutic targets and emphasizing the need for further research into the intricate molecular mechanisms underlying this debilitating syndrome.Aicardi-Goutières syndrome (AGS) is a rare genetic pediatric disorder currently associated with mu-tations in 9 genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, IFIH1, LSM11 and RNU7-1), all of which encode for proteins or transcripts involved in nucleic acid metabolism and signaling. In this thesis work, a pathologic variant of the RNU7-1 gene (AGS9) was analyzed. This gene encodes for the U7 small nucleolar RNA (U7 snRNA), an essential compo-nent of the U7 snRNP complex. The function of U7 snRNP is to operate the endonucleolytic cleavage of the poly-A tail in replication-dependent histones (RDHs) pre-mRNAs during their maturation process. RDHs genes encode the four core histones and the linker histone family. In AGS, mutations in RNU7-1 have been linked to defects in U7 complex synthesis, resulting in the production of aberrant RDHs isoforms that possess a poly-A tail. In this condition, chromatin is recognized as a foreign genome and acti-vates the innate immune cGAS-STING cascade, leading to increased type I IFN production and induction of transcription of interferon-stimulated genes (ISGs). As RNU7-1 (AGS9) is the least characterized AGS-related gene, the aim of this pro-ject is to dissect its role in AGS pathogenesis. To this end, this work both investigated canonical AGS features such as the potential upregulation of IFNα and ISGs, and spe-cific outcomes of a RNU7-1 pathologic variant in primary dermal fibroblasts obtained from an AGS9 patient and compared to a healthy age- and sex-matched control. Results of this thesis work pointed out an altered RNA morphology of U7 snRNA that leads to affects its subcellular localization in AGS9-derived fibroblasts. Moreover, al-tered expression of two AGS-related genes, (both the isoforms of ADAR1 and RNASEH2B) in fibroblasts carrying the pathologic variant of RNU7-1 was highlighted, confirming the strong cooperation between AGS genes in nucleic acid metabolism. The activation of the interferon signature (IS) in response to the mutation was ob-served, with upregulated ISGs and increased IFN score in fibroblasts and whole blood, reinforcing the connection between the RNU7-1 variant and interferon dysregulation. An anti-inflammatory compound, hydroxychloroquine, was then tested to determine its potential effectiveness in reducing IS and IFNα production. Results proven the de-crease of both ISGs and IFNα in AGS9 cells with also a partial restore of cell viability in AGS9 fibroblasts. As aberrant morphology of U7 snRNA could affect its functioning in U7 snRNP, RIP analysis was performed and a decrease in physical association between U7 snRNA and ZFP100 was reported. RNA-sequencing analysis then confirmed the alteration of multiple pathways related to neuron function and interferon signaling in AGS9 fibroblasts. Moreover, transcrip-tional changes in AGS9 cells were related to chromatin structural components. Spe-cifically, it was highlighted that genes involved in histone post-translational modifica-tions were strongly affected. Aberrant RDH histone processing was also confirmed through Real-Time qPCR, western blot and immunochemistry. Moreover, TEM anal-ysis reported a lack of chromatin in AGS9 nuclei, thus reinforcing RNAseq results. Since TEM analysis also revealed smaller mitochondria and reduced localization of ri-bosomes on ER membranes in AGS9 cells, Mitotracker, Mitosox and Click-iT staining assays were carried out to assess mitochondrial activity, ROS production and nascent protein production, respectively. Results demonstrated a reduced basal mitochondrial activity together with an increase production of ROS, and a reduced nascent protein production in AGS9 fibroblasts. In conclusion, these insights contribute to a more comprehensive characterization of AGS, shedding light on potential therapeutic targets and emphasizing the need for further research into the intricate molecular mechanisms underlying this debilitating syndrome

Multifocal versus monofocal intraocular lenses after cataract extraction.

BACKGROUND: Good unaided distance visual acuity is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: The objective of this review was to assess the effects of multifocal IOLs, including effects on visual acuity, subjective visual satisfaction, spectacle dependence, glare and contrast sensitivity, compared to standard monofocal lenses in people undergoing cataract surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1946 to March 2012), EMBASE (January 1980 to March 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 March 2012. We searched the reference lists of relevant articles and contacted investigators of included studies and manufacturers of multifocal IOLs for information about additional published and unpublished studies. SELECTION CRITERIA: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. DATA COLLECTION AND ANALYSIS: Two authors collected data and assessed trial quality. Where possible, we pooled data from the individual studies using a random-effects model, otherwise we tabulated data. MAIN RESULTS: Sixteen completed trials (1608 participants) and two ongoing trials were identified. All included trials compared multifocal and monofocal lenses but there was considerable variety in the make and model of lenses implanted. Overall we considered the trials at risk of performance and detection bias because it was difficult to mask patients and outcome assessors. It was also difficult to assess the role of reporting bias. There was moderate quality evidence that similar distance acuity is achieved with both types of lenses (pooled risk ratio (RR) for unaided visual acuity worse than 6/6: 0.98, 95% confidence interval (CI) 0.91 to 1.05). There was also evidence that people with multifocal lenses had better near vision but methodological and statistical heterogeneity meant that we did not calculate a pooled estimate for effect on near vision. Total freedom from use of glasses was achieved more frequently with multifocal than monofocal IOLs. Adverse subjective visual phenomena, particularly haloes, or rings around lights, were more prevalent and more troublesome in participants with the multifocal IOL and there was evidence of reduced contrast sensitivity with the multifocal lenses. AUTHORS' CONCLUSIONS: Multifocal IOLs are effective at improving near vision relative to monofocal IOLs. Whether that improvement outweighs the adverse effects of multifocal IOLs will vary between patients. Motivation to achieve spectacle independence is likely to be the deciding factor

Evaluation of non-viable biomass of Laurencia papillosa for decolorization of dye waste water

The uptake of fast orange dye by the red seaweed Laurencia papillosa has been demonstrated in order to explore its potential use as low-cost adsorbent. The adsorption kinetics of fast orange dye on the alga with respect to initial dye concentration, contact time, particle size and pH were investigated. The dye removal percentage increased from 25.92 to 67.08% and the equilibrium states were attained at almost 60 min within the experimental concentration range. The adsorption kinetic was analyzed using pseudo-first-order and pseudo-second-order models. The pseudo-second-order model was more appropriate to describe the sorption kinetics based on the relatively high values of the linear squared regression correlation coefficient. The nature of the possible adsorbent and fast orange interactions was examined by the Fourier transform infrared technique. This technique confirmed that hydroxyl, carboxyl, amine, sulfonyl, carbonyl and alkyl groups are responsible for the dye binding process. Significant increase in dye adsorption was observed with the decrease in sorbent particle size coupled with its large surface area. Maximum removal efficiency was determined to be 65.7% at a solution pH of 5. However, Laurencia papillosa proved to be a promising material for removing fast orange dye from aqueous solutions.Keywords: Dye adsorption, Macroalga, Laurencia papillosa, kineticsAfrican Journal of Biotechnology Vol. 12(17), pp. 2215-222

Cervical Length as a Predictor of Success of Induction of Labor in Term Pregnancy

Background: Vaginal delivery is the most important event occurring in women’s life. It carries many risks of significant concerns to the physicians. Predicting the chances of vaginal delivery is of paramount concern for the pregnant woman. Antenatal cervical length measurement has paramount importance in the prediction of labor.Objective: This study aimed to study the role of cervical length in prediction of success of induction of labor in term pregnancy.Patients and Methods: A prospective study where 140 pregnant women undergoing induction of labor for various indications were included, the cases were recruited from Obstetric Department of Shebin El-Kom Teaching Hospital in the period from October 2019 to December 2020.Results: Methods of induction was misoprostol in (75) females and amniotomy with oxytocin in (65) females. 97 Females were delivered by simple vaginal delivery, 79 females were delivered within 24 hours of induction, 18 females were delivered after 24 hours, and 43 females were delivered by caesarian section (C.S.). Indications of C.S. were mainly due to failed induction and fetal distress.Conclusions: We concluded that successful induction of labor was correlated significantly with detection of insulinlike growth factor-binding protein 1 (iGFBP-1) in cervical secretions and measurement of cervical length by transvaginal ultrasound (TVUS), IGFBP-1 detection by Actim Partus test is simple, easy bed side test that can predict successful induction of labor and measurement of cervical length by TVUS is a good predictor factor for successful induction of labor