Severe congenital neutropenia (Kostmann Syndrome)

Severe congenital neutropenia (SCN), Kostmann syndrome is a heterogenous disorder of myelopoiesis characterized by severe chronic neutropenia, absolute neutrophil count (ANC) persistently below 0.50 x 109/L, with maturation arrest of neutrophil precursors in the bone marrow; and associated with serious recurrent bacterial infections from early infancy. Sepsis mortality is reduced by an advent of granulocyte colony stimulating factor (G-CSF) therapy. More than 90% of patients respond to G-CSF therapy. However, hematopoietic stem cell transplantation has shown promise in the treatment of non-responders. About 60-80% of SCN cases are associated with constitutive mutations in one copy of the gene encoding neutrophil elastase ELA2. Myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) have been reported. The hazard of MDS/AML increases significantly overtime. Approximately 10% of patients with severe congenital neutropenia develop AML. This is not thought to be the direct result of G-CSF therapy but related to the underlying disease itself.Key Words: Myeloid leukemia, congenital neutropenia, kostmann’s syndrome, myelodysplastic syndrome

Integrated Pangenome Analysis and Pharmacophore Modeling Revealed Potential Novel Inhibitors against Enterobacter xiangfangensis

Enterobacter xiangfangensis is a novel, multidrug-resistant pathogen belonging to the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. However, there is currently no registered E. xiangfangensis drug on the market that has been shown to be effective. Hence, there is an urgent need to identify novel therapeutic targets and effective treatments for E. xiangfangensis. In the current study, a bacterial pan genome analysis and subtractive proteomics approach was employed to the core proteomes of six strains of E. xiangfangensis using several bioinformatic tools, software, and servers. However, 2611 nonredundant proteins were predicted from the 21,720 core proteins of core proteome. Out of 2611 nonredundant proteins, 372 were obtained from Geptop2.0 as essential proteins. After the subtractive proteomics and subcellular localization analysis, only 133 proteins were found in cytoplasm. All cytoplasmic proteins were examined using BLASTp against the virulence factor database, which classifies 20 therapeutic targets as virulent. Out of these 20, 3 cytoplasmic proteins: ferric iron uptake transcriptional regulator (FUR), UDP-2,3diacylglucosamine diphosphatase (UDP), and lipid-A-disaccharide synthase (lpxB) were chosen as potential drug targets. These drug targets are important for bacterial survival, virulence, and growth and could be used as therapeutic targets. More than 2500 plant chemicals were used to molecularly dock these proteins. Furthermore, the lowest-binding energetic docked compounds were found. The top five hit compounds, Adenine, Mollugin, Xanthohumol C, Sakuranetin, and Toosendanin demonstrated optimum binding against all three target proteins. Furthermore, molecular dynamics simulations and MM/GBSA analyses validated the stability of ligand–protein complexes and revealed that these compounds could serve as potential E. xiangfangensis replication inhibitors. Consequently, this study marks a significant step forward in the creation of new and powerful drugs against E. xiangfangensis. Future studies should validate these targets experimentally to prove their function in E. xiangfangensis survival and virulence

Wet Cupping Reduces Pain and Improves Health-related Quality of Life Among Patients with Migraine: A Prospective Observational Study

Objectives: To determine the benefits of wet cupping on pain and health-related quality of life (HRQOL) in adult patients with migraine headaches. Methods: We conducted a prospective observational study of wet cupping in 128 patients referred to the cupping clinic at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between January 2013 and December 2015. Bloodletting was performed at the base of the head and between the shoulders monthly four times. We assessed migraine headache pain using the visual analog scale (VAS) and the quality of life of patients before and after each cupping session using the World Health Organization Quality of Life assessment instrument. Results: The mean age of the patients was 40.5±11.3 years with a preponderance of females (n = 114, 89.1%). VAS was averaged at 7 before the procedure and reduced to 3 after wet cupping, both during rest and activity (p ≤ 0.005). Ninety-five patients agreed to complete the quality of life questionnaire. There was a significant improvement in the quality of life after wet cupping treatment in most of the displayed items (p < 0.050). None of the patients reported post-procedure complications. Conclusions: Wet cupping might be considered a complementary treatment for migraine headache pain relief and improvement to a patient’s quality of life

Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in Jeddah, Kingdom of Saudi Arabia

International audienceABSTRACT: BACKGROUND: The development of polymerase chain reaction (PCR)-based methods for the detection of known mutations has facilitated detecting specific red blood cell (RBC) enzyme deficiencies. We carried out a study on glucose-6-phosphate dehydrogenase (G6PD) deficient subjects in Jeddah to evaluate the molecular characteristics of this enzyme deficiency and the frequency of nucleotide1311 and IVS-XI-93 polymorphisms in the glucose-6-phosphate dehydrogenase gene. RESULTS: A total of 1584 unrelated Saudis (984 neonates and 600 adults) were screened for glucose-6-phosphate dehydrogenase deficiency. The prevalence of glucose-6-phosphate dehydrogenase deficiency was 6.9% (n=110). G6PD Mediterranean mutation was observed in 98 (89.1%) cases, G6PD Aures in 11 (10.0%) cases, and G6PD Chatham in 1 (0.9%) case. None of the samples showed G6PD A mutation. Samples from 29 deficient subjects (25 males and 4 females) were examined for polymorphism. The association of two polymorphisms of exon/intron 11 (c.1311T/IVS XI 93C) was observed in 14 (42.4%) of 33 chromosomes studied. This association was found in 9 (31.0%) carriers of G6PD Mediterranean and in 4 (13.8%) carriers of G6PD Aures. CONCLUSIONS: The majority of mutations were G6PD Mediterranean, followed by G6PD Aures and <1% G6PD Chatham. We conclude that 1311T is a frequent polymorphism in subjects with G6PD Mediterranean and Aures variants in Jeddah

Diosgenin alleviates D-galactose-induced oxidative stress in rats’ brain and liver targeting aging and apoptotic marker genes

The theory of aging is primarily concerned with oxidative stress caused by an imbalance in reactive oxygen species generation and cellular antioxidants. To alleviate the oxidative stress, we investigated the protective effect of diosgenin (DSG) for D-galactose (D-gal) using 20 and 40 mg of DSG/kg/day/orally for 42 days. The findings showed that D-gal caused brain and liver oxidative injuries by upregulating aging and oxidative markers. To counteract the oxidative stress caused by D-gal, DSG upregulated glutathione peroxidase-1, superoxide dismutase-1, and glutathione S-transferase-α. DSG also diminished the expression of p53, p21, Bcl-2-associated X protein, caspase-3, and mammalian target of rapamycin in brain and liver, as well as the build-up of β-galactosidase. DSG, in a dose-dependent manner, decreased the oxidative aging effects of D-gal in brain and liver tissues through targeting of aging and apoptotic marker genes. Finally, it should be noted that consuming DSG supplements is a suggesting natural preventative agent that may counteract aging and preserve health through improvement of body antioxidant status and control aging associated inflammation and cellular apoptosis

Insight into the phytochemical profile and antimicrobial activities of Amomum subulatum and Amomum xanthioides: an in vitro and in silico study

IntroductionMedicinal plants have been considered as potential source of therapeutics or as starting materials in drugs formulation.MethodsThe current study aims to shed light on the therapeutic potential of the Amomum subulatom and Amomum xanthioides Fruits by analyzing the phytochemical composition of their seeds and fruits using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) techniques to determine the presence of bioactive components such as flavonoids, phenols, vitamins, steroids, and essential oils.Results and DiscussionThe protein content is usually higher than the total lipids in both species except the fruit of A. subulatum which contain more lipids than proteins. The total protein contents for A. subulatum were 235.03 ± 21.49 and 227.49 ± 25.82 mg/g dry weight while for A. xanthioides were 201.9 ± 37.79 and 294.99 ± 37.93 mg/g dry weight for seeds and fruit, respectively. The Carvacrol levels in A. subulatum is 20 times higher than that in A. xanthioides. Lower levels of α-Thujene, Phyllanderenes, Ascaridole, and Pinocarvone were also observed in both species. According to DPPH (2,2-diphenylpicrylhydrazyl) assay, seed the extract of A. subulatum exhibited the highest antioxidant activity (78.26±9.27 %) followed by the seed extract of A. xanthioides (68.21±2.56 %). Similarly, FRAP (Ferric Reducing Antioxidant Power) assay showed that the highest antioxidant activity was exhibited by the seed extract of the two species; 20.14±1.11 and 21.18±1.04 µmol trolox g−1 DW for A. subulatum and A. xanthioides, respectively. In terms of anti-lipid peroxidation, relatively higher values were obtained for the fruit extract of A. subulatum (6.08±0.35) and the seed extract of A. xanthioides (6.11±0.55). Ethanolic seed extracts of A. subulatum had the highest efficiency against four Gram-negative bacterial species which causes serious human diseases, namely Pseudomonas aeruginosa, Proteus vulgaris, Enterobacter aerogenes, and Salmonella typhimurium. In addition, P. aeruginosa was also inhibited by the fruit extract of both A. subulatum and A. xanthioides. For the seed extract of A. xanthioides, large inhibition zones were formed against P. vulgaris and the fungus Candida albicans. Finally, we have in silico explored the mode of action of these plants by performing detailed molecular modeling studies and showed that the antimicrobial activities of these plants could be attributed to the high binding affinity of their bioactive compounds to bind to the active sites of the sterol 14-alpha demethylase and the transcriptional regulator MvfR.ConclusionThese findings demonstrate the two species extracts possess high biological activities and therapeutical values, which increases their potential value in a number of therapeutic applications

Molecular characterization of glucose-6-phosphate dehydrogenase deficient variants in Baghdad city - Iraq

Background: Although G6PD deficiency is the most common genetically determined blood disorder among Iraqis, its molecular basis has only recently been studied among the Kurds in North Iraq, while studies focusing on Arabs in other parts of Iraq are still absent. Methods: A total of 1810 apparently healthy adult male blood donors were randomly recruited from the national blood transfusion center in Baghdad. They were classified into G6PD deficient and non-deficient individuals based on the results of methemoglobin reduction test (MHRT), with confirmation of deficiency by subsequent enzyme assays. DNA from deficient individuals was studied using a polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) for four deficient molecular variants, namely G6PD Mediterranean (563 C®T), Chatham (1003 G®A), A- (202 G®A) and Aures (143 T®C). A subset of those with the Mediterranean variant, were further investigated for the 1311 (C®T) silent mutation. Results: G6PD deficiency was detected in 109 of the 1810 screened male individuals (6.0%). Among 101 G6PD deficient males molecularly studied, the Mediterranean mutation was detected in 75 cases (74.3%), G6PD Chatham in 5 cases (5.0%), G6PD A- in two cases (2.0%), and G6PD Aures in none. The 1311 silent mutation was detected in 48 out of the 51 G6PD deficient males with the Mediterranean variant studied (94.1%). Conclusions: Three polymorphic variants namely: the Mediterranean, Chatham and A-, constituted more than 80% of G6PD deficient variants among males in Baghdad. Iraq. This observation is to some extent comparable to othe

Prevalence and molecular characterization of Glucose-6-Phosphate dehydrogenase deficient variants among the Kurdish population of Northern Iraq

<p>Abstract</p> <p>Background</p> <p>Glucose-6-Phosphate dehydrogenase (G6PD) is a key enzyme of the pentose monophosphate pathway, and its deficiency is the most common inherited enzymopathy worldwide. G6PD deficiency is common among Iraqis, including those of the Kurdish ethnic group, however no study of significance has ever addressed the molecular basis of this disorder in this population. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis among Iraqi Kurds.</p> <p>Methods</p> <p>A total of 580 healthy male Kurdish Iraqis randomly selected from a main regional premarital screening center in Northern Iraq were screened for G6PD deficiency using methemoglobin reduction test. The results were confirmed by quantitative enzyme assay for the cases that showed G6PD deficiency. DNA analysis was performed on 115 G6PD deficient subjects, 50 from the premarital screening group and 65 unrelated Kurdish male patients with documented acute hemolytic episodes due to G6PD deficiency. Analysis was performed using polymerase chain reaction/restriction fragment length polymorphism for five deficient molecular variants, namely G6PD Mediterranean (563 C→T), G6PD Chatham (1003 G→A), G6PD A- (202 G→A), G6PD Aures (143 T→C) and G6PD Cosenza (1376 G→C), as well as the silent 1311 (C→T) mutation.</p> <p>Results</p> <p>Among 580 random Iraqi male Kurds, 63 (10.9%) had documented G6PD deficiency. Molecular studies performed on a total of 115 G6PD deficient males revealed that 101 (87.8%) had the G6PD Mediterranean variant and 10 (8.7%) had the G6PD Chatham variant. No cases of G6PD A-, G6PD Aures or G6PD Cosenza were identified, leaving 4 cases (3.5%) uncharacterized. Further molecular screening revealed that the silent mutation 1311 was present in 93/95 of the Mediterranean and 1/10 of the Chatham cases.</p> <p>Conclusions</p> <p>The current study revealed a high prevalence of G6PD deficiency among Iraqi Kurdish population of Northern Iraq with most cases being due to the G6PD Mediterranean and Chatham variants. These results are similar to those reported from neighboring Iran and Turkey and to lesser extent other Mediterranean countries.</p

Vermicompost Supply Modifies Chemical Composition and Improves Nutritive and Medicinal Properties of Date Palm Fruits From Saudi Arabia

To meet the increased demand for phytochemicals, plant cultivation in soil amended with biofertilizers has been developed. Here, we aimed to use vermicompost as an environmentally safe biofertilizer to enhance the nutritive and medicinal value of five common cultivars of Saudi date palm; namely Phoenix dactylifera L. var. Ajwa, Hulwa, Ruthana, Sefri, and Luban. To determine changes in the fruit nutritive composition, primary metabolites, antioxidants, phenolic compounds and mineral profiles were analyzed in the fruits from non-fertilized and vermicompost-fertilized date palms. We also tested how changes in the fruit chemical compositions due to vermicompost fertilization affected their medicinal potentials. Applying vermicomposts generally increased primary metabolites, vitamins, and mineral content as well as the medicinal potential of the date palm fruits. This positive effect is possibly explained by the role of vermicomposts in improving soil health and fertility. Furthermore, clustering analyses and principal component analysis (PCA) indicated cultivar-specific responses. PCA analysis also revealed that the bioactivities of the date palm fruit extracts and their antioxidants tended to display correlated output values. One of the highly accumulated phenolic compounds, β-D-glucogallin, was extracted and purified from P. dactylifera L. var. Ajwa fruits and showed significant antioxidant, anticancer, antibacterial, antimutagenic, and antiprotozoal activities. Overall, applying vermicompost is an innovative approach to increase the nutritive quality and medicinal potential of date palm fruits

Saudi SCD patients’ symptoms and quality of life relative to the number of ED visits

Background Individuals living with sickle cell disease (SCD) have significantly increased emergency department (ED) use compared to the general population. In Saudi Arabia, health care is free for all individuals and therefore has no bearing on increased ED visits. However, little is known about the relationship between quality of life (QoL) and frequency of acute care utilization in this patient population. Methods A cross-sectional study was conducted on 366 patients with SCD who attended the outpatient department at King Fahad Hospital, Hofuf, Saudi Arabia. Data were collected through self-administered surveys, which included: demographics, SCD-related ED visits, clinical issues, and QoL levels. We assessed the ED use by asking for the number of SCD-related ED visits within a 6-month period. Results The self-report survey of ED visits was completed by 308 SCD patients. The median number of SCD-related ED visits within a 6-month time period (IQR) was four (2-7 visits). According to the unadjusted negative binomial model, the rate of SCD-related ED visits increased by (46, 39.3, 40, and 53.5 %) for patients with fever, skin redness with itching, swelling, and blood transfusion, respectively. Poor QoL tends to increase the rate of SCD-related ED visits. Well education and poor general health positively influenced the rate of SCD-related ED visits. Well education tends to increase the rate of SCD-related ED visits by 50.2 %. The rate of SCD-related ED visits decreased by 1.4 % for every point increase in general health. Conclusion Saudi patients with sickle cell disease reported a wide range of SCD-related ED visits. It was estimated that six of 10 SCD patients had at least three ED visits within a 6-month period. Well education and poor general health resulted in an increase in the rate of SCD-related ED visits