Journals
2025 EN
Mahdi Ali · Rampotas Alexandros · Roberts Patrick
+15 more
ABSTRACT Introduction Myeloproliferative neoplasms (MPNs), such as polycythaemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF), are primarily treated by managing blood counts to reduce the thrombotic risk using cytoreductive agents. Busulphan, an oral alkylating agent, has been historically used for MPN management due to its myelosuppressive effects, but concerns about its risk of leukaemic transformation have limited its use. Methods This real‐world retrospective study evaluated the safety and efficacy of busulphan in 115 MPN patients across 13 UK hospitals. Responses in patients with ET and PV only were assessed using European LeukemiaNet (ELN) criteria. Results With a median age of 78 years, the overall response rate was 78.1%, with 29% of PV and 18% of ET patients achieving complete responses. Dosing regimens were similarly distributed between repeated single doses of busulphan (31%), courses of treatment lasting 1–4 weeks (30%) and continuous therapy for more than 4 weeks (35%). No cases of disease progression to acute leukaemia or myelofibrosis were recorded during the median follow‐up of 23 months. Adverse events were infrequent, with fatigue and cytopaenia being the most common (4% each). Conclusion Busulphan demonstrated a favourable safety profile and is a viable cytoreductive option, particularly for elderly patients who are intolerant to hydroxycarbamide. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission
Journals
2025 EN
Al Nabhani Ibrahim · Al Lawati Jaber · Al Mahrooqi Nooh
+14 more
ABSTRACT Objective There is a paucity of data on multiple myeloma (MM) from Oman and the region. This study reports the clinical presentation and survival outcomes in Omani patients with MM at Sultan Qaboos University Hospital (SQUH), a tertiary care academic center. Methods This retrospective included all patients diagnosed, treated, and followed up for MM at SQUH between June 2008 and December 2018. Patient demographics, disease characteristics, clinical presentation, prognostic parameters, and survival data were obtained from the patients’ electronic medical records. The Kaplan‐Meier method was used to estimate the progression‐free survival (PFS) and overall survival (OS), and the log‐rank test was used to compare survival according to the international staging system (ISS) stage. Results Ninety‐eight patients were analyzed, 49 (50%) of whom were males. The median age was 61 years (range: 30–88). Immunoglobulin G (IgG) was the most common subtype of myeloma (59.6%), followed by IgA (24.2%) and IgD (4%). Twelve patients (12%) had light chain myeloma. The most common manifestation of myeloma at the time of initial diagnosis was anemia (50%), followed by lytic lesions (41.5%), renal insufficiency (24.2%), and hypercalcemia (23.2%). Forty‐three patients (44%) had ISS stage III disease at presentation. Over the study period, patients received different types of induction therapy. Ninety patients received therapy at SQUH and had complete data on first‐line treatment. Thirty‐six patients (41%) received proteasome inhibitor (PI) based regimens, 23 patients (25%) had immunomodulatory‐based (IMID‐based) therapy, and 23 patients (25%) had combination PI and IMiD‐based induction therapy. For patients with complete data on treatment, responses and outcome ( n = 90), after a median follow‐up of 76 months (95% confidence interval [CI]: 54–97 m), median PFS was 59 months (95% CI: 20.1–78), with an estimated five year PFS of 41%. Median OS was 109 months (95% CI: 65–173) with a 5‐year OS of 61%. ISS stage predicted OS (ISS stage I and stage II: 133 m, 95% CI: 94–173 m, stage III: 36 m, 95% CI: 25–47 m; log‐rank p < 0.001) but not PFS. Conclusion The median age of our patients is younger than what is published in the literature. Most of our patients presented with advanced‐stage disease, which was predictive of survival in our cohort. The lack of uniformity of treatment and the small number of patients precluded concluding the effect of treatment on survival. Collaboration with other centers in Oman and the region to collect retrospective and prospective data on a larger cohort of patients is recommended. Clinical Trial Registration The authors have confirmed that clinical trial registration is not needed for this submission.
Journals
2025 EN
Darwish Shaban A. · Abbas Ashraf A. · ElSayed Ibrahim ElTantawy
+2 more
ABSTRACT Treatment of isoquinoline with some N,N ‐disubstituted α ‐bromoacetamide compounds afforded the corresponding isoquinolinium bromides having the electron‐rich carbazolyl, diphenylamino, and diisopropylamino moieties. The isoquinolinium salts were subjected to a heteroannulation process via a reaction with some dipolarophiles under basic medium to generate the corresponding pyrrolo[2,1‐ a ]isoquinoline‐3‐carboxamide derivatives via [3 + 2] cycloaddition reaction. The obtained compounds were characterized using the appropriate spectroscopic techniques.
Journals
2025 EN
AbdelMegid Mohamed · Ali Tarik E. · Salem Mostafa E.
+3 more
ABSTRACT Recent examples provide clear evidence that ring‐chain tautomerism can be exploited successfully in the synthesis of wide varieties of five‐membered heterocyclic systems. Owing to the versatile chemotherapeutical activities of azoles, the current review mainly focused on employing the ring‐chain tautomeric phenomenon in synthesizing azoles, the five‐membered heterocyclic systems having two hetero‐atoms such as pyrazoles, isoxazoles, oxazoles, imidazoles, thiazoles. Moreover, we discuss the simultaneous existence of ring‐chain tautomerism in two similar or different five‐membered heterocycles, which is known as ring‐ring tautomerism. Also, the three‐, four‐ and five‐component equilibria are reported. In addition, the biological activities of the target azoles are reported.
Journals
2025 EN
Diab Hadeer M. · Ali Doaa Hassan · Abdallah Tayseer A.
+5 more
ABSTRACT In this study, we have developed new hybrid compounds by connecting bis‐heterocycles with a 2,3‐diphenoxyquinoxaline core. This is performed by combining 4,4′‐(quinoxaline‐2,3‐diylbis(oxy))dibenzaldehyde with the necessary reagents via Hantzsch and Biginelli reactions. The newly synthesized compounds' structures are determined by elemental analysis, 1 H NMR, 13 C NMR, IR, and MS spectra. The tested compound 18 has the strongest antibacterial activities against S. aureus and E. coli , with inhibition zones of 18 and 14.67 mm, respectively. The tested compound 5 exhibited the strongest antibacterial activities against S. aureus , with an inhibition zone of 17 mm. Molecular docking studies of the most efficient compounds were performed against two proteins, including ATP‐dependent Clp protease ATP‐binding subunit ClpA (UniProt ID: P0ABH9) and Glycerol dehydrogenase (GDH) (UniProt ID: P0A9S5). Compound 5 interacted with the ClpA active site, exhibiting a binding score of ∆G = −9.2 Kcal/mol, while 18 interacted with the GDH active site, exhibiting a binding score of ∆G = −11.4 Kcal/mol.
Journals
2025 EN
Okumu Ibrahim Mike · Nathan Sunday · Bbaale Edward
ABSTRACT This article examines how corruption relates to a firm's decision to invest and the value of investment. We use data from the World Bank Enterprise Survey (WBES) of firms in Sub‐Saharan Africa (SSA), surveyed between 2010 and 2017. We adopt an instrumental variable approach to address the endogeneity problem. Our results suggest that lower levels of bribe payments enable firms to circumvent bureaucratic hurdles, thus facilitating investment decisions. However, at higher levels of corruption, the relationship is inverse. Corruption distorts the value of firm investment, especially among small firms, those in the manufacturing sector rather than service, and both young and mature firms. The distortionary effects of corruption are worsened by credit constraints. Our findings reaffirm the importance of SSA countries strengthening their fight against corruption to boost firm investment and economic transformation, especially given the dominance of small firms.
Journals
2025 EN
Adly Amira Abdel Moneam · Ismail Eman Abdel Rahman · Ibrahim Fatma A.
+3 more
Abstract Enzymatic deficiency in Gaucher disease (GD) may induce oxidative stress. Vitamin E is the nature's most effective lipid‐soluble antioxidant. This prospective clinical trial assessed the oxidant‐antioxidant status in Egyptian patients with GD and the efficacy and safety and of vitamin E as an adjuvant antioxidant therapy. Forty children and adolescents with GD on stable doses of enzyme replacement therapy (ERT) were enrolled. Abdominal ultrasonography and transient elastography were performed. Malondialdehyde (MDA), vitamin E, and antioxidant enzymes (reduced glutathione [GSH], superoxide dismutase [SOD], glutathione peroxidase [GPx], and peroxiredoxin 2 [PRDX2]) were assessed. Patients were compared with 40 age‐ and sex‐matched healthy controls. Patients with GD were randomized either to receive oral vitamin E for 6 months or not. All patients with GD had significantly higher MDA levels with lower levels of vitamin E and antioxidant enzymes compared with healthy controls ( p < 0.001). Vitamin E and PRDX2 were negatively correlated to severity score index (SSI), lyso GL1, and MDA. After 6 months of vitamin E supplementation, SSI and liver and spleen volumes and liver stiffness were significantly lower. Lyso GL1 and MDA were significantly decreased post‐vitamin E therapy while antioxidant enzymes were significantly higher compared with baseline levels and with patients without vitamin E therapy. Oxidative stress is related to disease severity in pediatric patients with GD. A 6‐month vitamin E supplementation for those patients represents a safe therapeutic adjuvant agent increasing the efficacy of ERT, reducing oxidative stress, and improving outcomes.
Journals
2025 EN
Meldau Surita · McCormick Elizabeth M. · GeorgeSankoh Ibrahim
+7 more
ABSTRACT Primary mitochondrial diseases (PMD) are caused by pathogenic variants in over 350 genes, 37 of which are located in mitochondrial DNA (mtDNA). While more than 100 mtDNA variants have confirmed disease associations, there are few reports of mtDNA‐related PMD in patients with African heritage, even in well‐studied populations. We investigated the frequency of pathogenic mtDNA variants in African L‐haplogroups in patients with confirmed PMD from two diagnostic cohorts. Data from genetically confirmed mtDNA‐related cases were extracted from existing databases at the National Health Laboratory Service Inherited Metabolic Disease Laboratory in South Africa (SA), and the Children's Hospital of Philadelphia (CHOP) Mitochondrial Medicine Frontier Program (USA). Mitochondrial genome haplogroup context was recorded from existing sequence report data. Stored DNA from the remaining cases was sequenced for mitochondrial genome haplogroup determination. Haplogroup context was obtained for 82 SA and 165 CHOP PMD cases. Sixty‐two (47 SA; 15 USA) PMD cases from at least 50 maternal lineages were found to carry L Haplogroups. Unique L sub‐haplogroups were identified in 11 (9 SA, 2 USA) families with the m.3243A>G MELAS variant, 6 SA families with the m.11778G>A LHON variant, and 20 (15 SA, 5 USA) cases with single large‐scale mtDNA deletions (4 of whom had the 4977 bp common deletion). Several additional well‐documented mtDNA pathogenic variants were identified in L‐haplogroup context. PMD patient clinical features correlated closely with those described in other haplogroup cohorts. This study demonstrates that common pathogenic mtDNA variants occur in the context of multiple African mtDNA lineages. Disproportionately low diagnostic rates highlight ongoing diagnostic inequalities affecting those on the African continent and African patients globally.
Journals
2025 EN
Uba Abdullahi Ibrahim
ABSTRACT Due to its intricate molecular and structural characteristics, vascular endothelial growth factor receptor 2 (VEGFR‐2) is essential for the development of new blood vessels in various pathological processes and conditions, especially in cancers. VEGFR‐2 inhibitors have demonstrated significant anticancer effects by blocking many signaling pathways linked to tumor growth, metastasis, and angiogenesis. Several small compounds, including the well‐tolerated sunitinib and sorafenib, have been approved as VEGFR‐2 inhibitors. However, the widespread side effects linked to these VEGFR‐2 inhibitors—hypertension, epistaxis, proteinuria, and upper respiratory infection—motivate researchers to search for new VEGFR‐2 inhibitors with better pharmacokinetic profiles. The key molecular interactions required for the interaction of the small molecules with the protein target to produce the desired pharmacological effects are identified using computer‐aided drug design (CADD) methods such as pharmacophore and QSAR modeling, structure‐based virtual screening, molecular docking, molecular dynamics (MD) simulation coupled with MM/PB(GB)SA, and other computational strategies. This review discusses the applications of these methods for VEGFR‐2 inhibitor design. Future VEGFR‐2 inhibitor designs may be influenced by this review, which focuses on the current trends of using multiple screening layers to design better inhibitors.
Journals
2025 EN
AlAsmar Asmaa · Kittaim · Mayyala Abdallatif
+2 more
ABSTRACT Bioanalytical method development and validation are essential for reliable quantification of drugs in biological matrices. This research focuses on developing and validating a UPLC‐MS/MS method for the simultaneous determination of bisoprolol and hydrochlorothiazide in human plasma, adhering to established regulatory guidelines for bioanalytical method validation. The development and validation focus on creating a robust and sensitive assay suitable for bioequivalence studies and routine therapeutic drug monitoring. This method utilizes bisoprolol D5 and hydrochlorothiazide C13 D2 as internal standards to enhance accuracy and precision. Chromatographic separation was achieved on a Waters Acquity UPLC BEH C18 column (100 × 2.1 mm, 1.7 μm particle size) with an isocratic mobile phase consisting of 10 mM ammonium formate buffer, methanol, and 0.1% ammonia solution (10:90, v/v). The flow rate was set at 0.3 mL/min, with a retention time of 2.2 min. Multiple reaction monitoring (MRM) was used with positive ESI for bisoprolol (m/z 326.36 → 116.13, internal standard m/z 331.36 → 121.13) and negative ESI for hydrochlorothiazide (m/z 296.11 → 269.00, internal standard m/z 299.11 → 270.00). The analytes and their respective internal standards were co‐extracted using a liquid–liquid extraction method with tert ‐butyl methyl ether as the extraction solvent. Linearity for bisoprolol and hydrochlorothiazide was maintained over a concentration range of 1–100 ng/mL for bisoprolol and 1.0–300 ng/mL for hydrochlorothiazide, respectively, using a weighted least squares linear regression model (1/x). This method achieved a lower limit of quantification (LLOQ) of 1.0 ng/mL, making it highly sensitive for the detection of these analytes. Moreover, the method demonstrated high accuracy, precision, selectivity, and reduced overall analysis time, making it well suited for routine analysis and bioequivalence studies of 10 mg bisoprolol and 25 mg hydrochlorothiazide tablets.