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51.
Marta Clariano Vanda Marques João Vaz Salma Awam Marta B. Afonso Maria Jesus Perry Cecília MP Rodrigues 《化学与生物多样性》2023,20(3):e202300222
Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile. 相似文献
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53.
Dorota?MoniesEmail author Hindi?N.?Alhindi Mohamed?A.?Almuhaizea Mohamed?Abouelhoda Anas?M.?Alazami Ewa?Goljan Banan?Alyounes Dyala?Jaroudi Abdulelah?AlIssa Khalid?Alabdulrahman Shazia?Subhani Mohamed?El-Kalioby Tariq?Faquih Salma?M.?Wakil Nada?A.?Altassan Brian?F.?Meyer Saeed?Bohlega 《Human genomics》2016,10(1):32
Background
Fifty random genetically unstudied families (limb-girdle muscular dystrophy (LGMD)/myopathy) were screened with a gene panel incorporating 759 OMIM genes associated with neurological disorders. Average coverage of the CDS and 10 bp flanking regions of genes was 99 %. All families were referred to the Neurosciences Clinic of King Faisal Specialist Hospital and Research Centre, Saudi Arabia. Patients presented with muscle weakness affecting the pelvic and shoulder girdle. Muscle biopsy in all cases showed dystrophic or myopathic changes. Our main objective was to evaluate a neurological gene panel as a first-line diagnostic test for LGMD/myopathies.Results
Our panel identified the mutation in 76 % of families (38/50; 11 novel). Thirty-four families had mutations in LGMD-related genes with four others having variants not typically associated with LGMD. The majority of cases had recessive inheritance with homoallelic pathogenic variants (97.4 %, 37/38), as expected considering the high rate of consanguinity in the study population. In one case, we detected a heterozygous mutation in DNAJB responsible for LGMD-1E. Our cohort included seven different subtypes of LGMD2. Mutations of DYSF were the most commonly identified cause of disease followed by that in CAPN3 and FKRP. Non-LGMD myopathies were due to mutations in genes associated with congenital disorder of glycosylation (ALG2), rigid spine muscular dystrophy 1 (SEPN1), inclusion body myopathy2/Nonaka myopathy (GNE), and neuropathy (WNK1). Whole exome sequencing (WES) of patients who remained undiagnosed with the neurological panel did not improve our diagnostic yield.Conclusions
Our neurological panel achieved a high clinical sensitivity (76 %) and is an effective first-line laboratory test in patients with LGMD and other myopathies. This sensitive, cost-effective, and rapid assay significantly assists clinical practice especially in these phenotypically and genetically heterogeneous disorders. Moreover, the application of the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) guidelines applied in the classification of variant pathogenecity provides a clear interpretation for physicians on the relevance of such findings.54.
55.
Bilal Hussain Tayyaba Sultana Salma Sultana N. Al-Mulhim Shahid Mahboob 《Saudi Journal of Biological Sciences》2018,25(7):1326-1331
This study’s objective was to assess a seasonal impact of industrial and sewage waste disposal on water quality of the river upstream Trimu Head. Considering the significance of the river, drain wastewater was analyzed during the summer and the winter seasons from pre-determined locations. Water quality parameters were recorded higher than the maximum permissible limits prescribed by WHO for freshwater bodies. Level of these Physio-chemical variables was higher in the winter due to the least amount of water from domestic sewage. Although some of these parameters indicated sedimentation hitherto the water quality of River Chenab was found very poor due to the pollution bestowed by tributary waste water from drains. Findings of this investigation suggest the importance of continuous monitoring and assessment to improve the water quality of the river. This study provides a baseline data which may be compared to assess any further deterioration in the water quality and may also be used to plan future monitoring and required restoration of habitat for the safe supply of fish to the population of this region. 相似文献
56.
Jameela?M.A. Shinwari Arif Khan Salma Awad Zakia Shinwari Ayodele Alaiya Mohamad Alanazi Asma Tahir Coralie Poizat Nada Al?Tassan 《American journal of human genetics》2015,96(1):147-152
Abnormal ocular motility is a common clinical feature in congenital cranial dysinnervation disorder (CCDD). To date, eight genes related to neuronal development have been associated with different CCDD phenotypes. By using linkage analysis, candidate gene screening, and exome sequencing, we identified three mutations in collagen, type XXV, alpha 1 (COL25A1) in individuals with autosomal-recessive inheritance of CCDD ophthalmic phenotypes. These mutations affected either stability or levels of the protein. We further detected altered levels of sAPP (neuronal protein involved in axon guidance and synaptogenesis) and TUBB3 (encoded by TUBB3, which is mutated in CFEOM3) as a result of null mutations in COL25A1. Our data suggest that lack of COL25A1 might interfere with molecular pathways involved in oculomotor neuron development, leading to CCDD phenotypes. 相似文献
57.
Gilbert F Azmeh S Barnard C Behnke J Collins SA Hurst J Shuker D 《Animal behaviour》2001,61(1):217-229
The marking of flowers with ephemeral scent is an underappreciated but vital element in the foraging behaviour of social bees. Using observational and experimental data, we tested whether a solitary bee (female Anthophora plumipes) uses scent marking while foraging on flowers of Cerinthe major in Portugal. Females used scent marks with at least two components that differed in their volatility and, furthermore, recognized the marks of different individuals. A very short-term component (<3 min) was attractive, resulting in the observed high level of immediate revisits: this component appeared to be adjusted according to the foraging needs of the moment. A longer-term component (<30 min) was initially repellent and matched the rate of nectar renewal; it, or the response to it, also appeared to be adjusted to the perceived level of nectar reward. There may be even longer-term effects associated with the specific foraging areas of individual bees. Observed differences in the way in which individuals responded to scent marks indicate that they may play a role as part of a dominance or exclusion mechanism among females. Copyright 2001 The Association for the Study of Animal Behaviour. 相似文献
58.
Walid Saibi Salma AbdeljalilKhaled Masmoudi Ali Gargouri 《Biochemical and biophysical research communications》2012,426(3):289-293
The chemical industry has come under increasing pressure to make chemical production more eco-friendly and independent to fossil resources. The development of industrial processes based on micro-organisms can especially help to eliminate the use or the generation of hazardous substances and can support the transition from dependence on fossil resources towards real sustainable and eco-safety industrial processes. The biocatalysts are the best solution given by nature that can be used to improve some biotechnological applications. In this research review, we report some peculiar properties of biocatalysts, implicated in a range of metabolic pathways and biotechnological tools. 相似文献
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60.
Adnan A. Bekhit Hayam M. A. Ashour Hamdy M. Abdel-Rahman Salma A. Bekhit 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):296-309
Four series of pyrazolylbenzenesulfonamide derivatives were synthesized and evaluated for their anti-inflammatory activity using cotton pellet induced granuloma and carrageenan-induced rat paw edema bioassays. Moreover, COX-1 and COX-2 inhibitory activity, ulcerogenic effect and acute toxiCIT000y were also determined. Furthermore, the target compounds were screened for their in-vitro antimicrobial activity against Eischerichia coli, Staphylococcus aureus and Candida albicans. Compounds 4-(3-Phenyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9a and 4-(3-Tolyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9b were not only found to be the most active dual anti-inflammatory antimicrobial agents in the present study with good safety margin and minimal ulcerogenic effect but also exhibited good selective inhibitory activity towards COX-2. A docking pose for 9a and 9b separately in the active site of the human COX-2 enzyme was also obtained. Therefore, these compounds would represent a fruitful matrix for the development of dual anti-inflammatory antimicrobial candidates with remarkable COX-2 selectivity. 相似文献