Journals
2026 EN
Aidy Esraa A. · Elmongy Elshaymaa I. · Ahmed Abdullah A. S.
+6 more
ABSTRACT This work describes the design, synthesis, and anticancer evaluation of a new acridine hybrid (ACNP). ACNP showed cytotoxic effect with IC 50 values of 4.3 and 10 μg/mL against MCF‐7 and MDA‐MB 231; respectively, versus CC 50 value of 439.72 μg/mL of normal lung fibroblast cells (WI‐38 cells) with high selectivity index (SI) of 102.2 and 43.9 for MCF‐7 and MDA‐MB 231 of cancer cells respectively. ACNP showed a cytotoxic synergetic effect when combined with paclitaxel in MDA‐MB 231 and MCF‐7 cell lines. A significant down regulation of PI3K, mTOR and AKT was demonstrated in cells treated with paclitaxel or ACNP as single therapy with minimal expression in cells treated with combination of both. ACNP treated cells recorded an increase in protein expression level of Caspase‐3, Caspase‐9 while Ki67 showed a declined expression in MDA‐MB 231 and MCF‐7 cell lines. Molecular docking investigation was performed on PI3K and Caspase‐3 to predict the possible binding modes of the acridine tricyclic skeleton with the molecular targets. The ADME study revealed that ACNP has high GI absorption and blood brain barrier although oral bioavailability was poor. These results suggested that ACNP maybe a promising candidate for further preclinical development.
Journals
2026 EN
Alsfouk Aisha A. · Elkaeed Eslam B. · Elkady Hazem
+8 more
ABSTRACT In this study, a series of novel thiadiazole derivatives ( 7a , 7b , 9a , 9b , and 9c ) were rationally designed as potential VEGFR‐2 inhibitors using a pharmacophore‐guided strategy. The compounds were synthesized and assessed for their antiangiogenic and anticancer effects. Among them, compound 9b showed the strongest VEGFR‐2 inhibition (IC 50 = 0.030 ± 0.001 μM), outperforming the reference drug Sorafenib. Cytotoxicity tests revealed that 9b was highly effective against MCF‐7 breast cancer cells (IC 50 = 8.06 ± 0.7 μM) while exhibiting minimal toxicity toward normal WI‐38 cells. Flow cytometry demonstrated that 9b induced significant G2/M cell cycle arrest and increased apoptosis, supported by molecular data showing upregulation of caspase‐3 and Bax and downregulation of Bcl‐2, indicating activation of the intrinsic apoptotic pathway. Extensive in silico studies—including molecular docking, 200 ns molecular dynamics simulations, interaction mapping, principal component analysis of trajectories, and free energy landscape analysis—confirmed that 9b binds stably and efficiently within the VEGFR‐2 active site. Overall, these results highlight compound 9b as a promising VEGFR‐2‐targeted antiangiogenic agent with potent enzymatic and cellular activity, favorable selectivity, and mechanistic validation through combined experimental and computational approaches.
Journals
2026 EN
Esener Zeynep · Yücesoy Mehmet Akif · Gezdirici Alper
+11 more
ABSTRACT Hypohidrotic ectodermal dysplasias are a genetic condition affecting ectoderm‐derived structures such as hair, teeth, nails, and sweat glands, resulting from variations in the EDA , EDAR , EDARADD , and WNT10A genes. This study examined 32 cases from 25 unrelated families from Türkiye, identifying seven novel variants in the EDA , EDAR , and WNT10A genes. The distribution of genetic alterations across the cohort revealed that 44% of the families (11/25) harbored variants in EDA, whereas EDAR and WNT10A variants were identified in 32% (8/25) and 24% (6/25) of families, respectively. Clinical evaluation revealed the characteristic hypohidrotic ectodermal dysplasia triad of hypotrichosis, hypodontia, and hypohidrosis was observed in 87.5% of cases, along with other symptoms such as dry skin, atopic dermatitis, and developmental delays. All cases presented with hair, eyebrow, and eyelash abnormalities, ranging in severity from subtle thinning to marked hypotrichosis. Among the cohort, one case exhibited severe atopic dermatitis as the predominant symptom. Targeted next‐generation sequencing and clinical exome sequencing were employed to determine the genetic basis of the condition, emphasizing the importance of early diagnosis for targeted interventions. This study expands the genetic and phenotypic spectrum of hypohidrotic ectodermal dysplasia, presenting a comprehensive overview of molecular findings and genotype–phenotype correlations in the population from the Turkish population.
Journals
2026 EN
AbdulWahab Atqah · Mohamed Reem · Hamid Amani
+5 more
ABSTRACT Primary ciliary dyskinesia (PCD) is a genetic disease caused by variants affecting more than 50 cilia genes. We report the prevalence and distribution of all known and novel variants in children with PCD in Qatar. The cohort included 28 children: 16 Qatari, 3 Egyptian, 2 Tunisian, 1 Sudanese, 1 Algerian, 1 Pakistani, 2 Iranian, and 2 Indian. Consanguinity rate was 82.1%. Median age at diagnosis was 7.5 years (IQR: 0.6–11.8). Situs inversus was present in 7 (25%) patients, chronic cough in 25 (89.3%), chronic sinusitis in 17 (60.7%), and bronchiectasis in 16 (61%). Median FEV1 was 71% (IQR: 58%–82%), FVC was 80% (IQR: 74%–91%), and FEV1/FVC ratio was 79% (IQR: 68%–84%). The most frequent variant in native Qataris was c.5924+1G>C in DNAH11 (seven patients). Eight novel variants were found in the cohort: c.6565C>T in DNAH11 (two patients); c.368‐369del in DNAAF3 (one patient); c.357G>A in DNAFF2 (one patient); c.278G>A in DNAAF2 (one patient); c.1666‐9C>G (intronic) in CCDC39 (two patients); c.9105+2T>C (splice donor) in DNAH5 (two patients); c.8647+3A>G (intronic) in DNAH5 (two patients); c.916G>T in ODAD4 gene (two patients). Wide genetic variation was found among PCD children in Qatar, including several novel variants, reflecting their ethnic diversity. Genetic variation was less among native Qatari patients due to high consanguinity.
Journals
2026 EN
UnselBolat Gul · Bolat Hilmi · Citli Senol
+2 more
ABSTRACT The RAR‐related orphan receptor alpha ( RORA ) gene encodes a nuclear receptor involved in transcriptional regulation, circadian rhythm, and neurodevelopment. Dominant RORA variants are associated with intellectual developmental disorder with or without epilepsy or cerebellar ataxia, yet the phenotypic spectrum remains poorly defined. We performed comprehensive genetic and clinical analyses in four individuals with RORA variants from three unrelated families, using whole exome sequencing and chromosomal microarray analysis. Identified variants were confirmed by Sanger sequencing. Genetic analyses revealed three distinct RORA variants: a 15q21.2–q22.2 deletion encompassing RORA , a de novo nonsense variant c. 499C >T (p.Gln167*), and a novel heterozygous frameshift variant c.683_686del (p. Glu228Valfs *78) segregating within a family. Clinical findings ranged from severe neurodevelopmental delay and epilepsy to mild intellectual disability and behavioral abnormalities, demonstrating marked intrafamilial variability. Notably, the same frameshift variant presented with differing phenotypes in the family, indicating variable expressivity—the first such observation reported in RORA ‐related disorders. Our findings broaden the genotypic and phenotypic spectrum of RORA ‐related neurodevelopmental disorders. The observed intrafamilial variability highlights the complexity of RORA‐associated pathogenesis and underscores the importance of considering variable expressivity in future genotype–phenotype studies.
Journals
2026 EN
Fettouh Ahmed Ibrahim Aboul · Ghallab Noha Ayman · Adel Nael
+4 more
ABSTRACT Introduction This randomized clinical trial aimed to evaluate implant stability following graftless lateral window and crestal implant approaches for maxillary sinus floor elevation (MSFE) 1 year after implant placement. Methods Twenty‐six single missing posterior maxillary teeth indicated for delayed implant placement, with a residual ridge height of 4–6 mm, were randomly assigned to perform either graftless lateral window (control) or crestal implant (test) approaches for MSFE. Implant stability was assessed using resonance frequency analysis; intra‐sinus vertical bone gain and marginal bone loss were measured via CBCT 1 year after implant placement. Clinical parameters and patient‐reported outcomes were also measured. Results The reported implant stability quotient (ISQ) values were not significantly different between the lateral window and the crestal implant approaches (80.92 ± 4.57 and 80.19 ± 7.28, respectively) 12 months after implant placement. However, the lateral window approach revealed a significant increase ( p < 0.001) in the mean ± SD intra‐sinus vertical bone gain at 6 and 12 months (3.64 ± 0.84 mm and 3.82 ± 0.84 mm, respectively) compared to the crestal implant approach (1.66 ± 1.27 mm and 2.42 ± 1.39 mm, respectively). However, no intergroup significant difference was noticed concerning average marginal bone loss ( p = 0.31) after 12 months. Postoperative complications and patient discomfort were more evident in the lateral window approach group. Conclusion In patients with a residual ridge height of 4–6 mm receiving implant therapy in conjunction with maxillary sinus elevation without graft material, there was no statistically significant difference in implant stability at 12 months between a lateral window and transcrestal sinus approach. Greater vertical bone gain was achieved following the lateral window approach.
Journals
2026 EN
Güver Çalapkulu İrem Damla · Paksoy Zehra Betul · Sevim İbrahim
+1 more
ABSTRACT Objective This study aimed to evaluate the long‐term effects of upper airway surgery on olfactory (orthonasal and retronasal) and gustatory functions in patients with obstructive sleep apnoea syndrome (OSAS). Sensory outcomes were compared between surgically treated patients and newly diagnosed OSAS patients who had not received surgery or Positive Airway Pressure (PAP) therapy. In addition, the influence of surgical technique on investigated parameters was analyzed. Materials and Methods This prospective study included 49 patients aged 18–75 years with OSAS, divided into a surgical group ( n = 25) and a control group ( n = 24). The surgical group had undergone at least one of the following procedures more than 1 year prior: anterior palatoplasty, expansion sphincter pharyngoplasty, lateral pharyngoplasty, tongue base coblation, or epiglottopexy. Orthonasal olfaction was assessed using the Connecticut Chemosensory Clinical Research Centre (CCCRC) test; retronasal olfaction using a validated 20‐item powder‐based test; and gustatory function with taste strips for sweet, salty, sour, and bitter. Results There were no significant differences between the surgery and control groups in terms of age, apnoea–hypopnoea index (AHI), retronasal olfactory scores, orthonasal threshold, identification, mean CCCRC scores, or gustatory scores ( p = 0.218, 0.912, 0.464, 0.111, 0.952, 0.423, and 0.738, respectively). In contrast, a strong and statistically significant correlation was found between retronasal and mean CCCRC scores (Spearman's r = 0.653, p < 0.001). Conclusion Upper airway surgery does not appear to adversely affect long‐term olfactory or gustatory function in OSAS patients. The high correlation between orthonasal and retronasal scores supports their combined use in sensory evaluation. These findings suggest that surgery is safe with regard to smell and taste perception.
Journals
2026 EN
Özkaya Esen · Erdem Yasemin · Aydoğdu İbrahim Halil
+1 more
ABSTRACT Background Allergic contact dermatitis (ACD) is a rare but significant cause of hand eczema (HE). Objectives To evaluate positive patch test reactions in HE patients, focusing on frequency, clinical/occupational relevance and sources of exposure at a tertiary referral centre in Turkey. Methods Retrospective analysis of 1499 HE patients from 2533 consecutively patch‐tested individuals (1996–2021). Results Positive patch test reactions occurred in 55.6% of HE patients, most commonly to nickel sulphate, potassium dichromate and thiuram mix. ACD was diagnosed in 34.2% of cases, with 54.1% being occupational, mainly in males. Occupational ACD was predominantly associated with potassium dichromate/cement among construction workers, and thiurams/rubber gloves among construction and healthcare workers. Non‐occupational ACD (45.9%) was more frequent in females, typically associated with methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), MI and fragrances in cosmetics and personal care products. Nickel was not a leading cause of HE; however, it was the inducer of systemic allergic dermatitis in 2.7% (14/512) of patients with hand ACD. Recurrent vesicular HE and bilateral dorsal, periungual, or wrist involvement were significantly associated with ACD. Conclusions Nickel was a frequent sensitiser but an uncommon cause of hand ACD, often triggering systemic allergic dermatitis. Occupational ACD and male gender predominated. Recurrent vesicular HE and bilateral dorsal, periungual, or wrist involvement were key patterns helping identify patients for patch testing.
Journals
2026 EN
Duran Ibrahim · Schafmeyer Leonie · Lentzen Bruno
+4 more
Abstract Aim To establish novel longitudinal reference values for the Gross Motor Function Measure‐66 (GMFM‐66) in children and adolescents with cerebral palsy aged 3 to 18 years, to enable more accurate assessments of changes in motor function. Method This was a single‐centre retrospective analysis of patients who participated in a rehabilitation programme between January 2006 and March 2022. The GMFM‐66 was used to measure gross motor function. Paired GMFM‐66 measurements from the follow‐up phase of the rehabilitation programme were used to establish a reference centile for the change in GMFM‐66 over a 6‐month period using the lambda–mu–sigma method. Results Reference centiles for GMFM ‐66 changes (over a 6‐month period; ±1 month) were created using 1190 longitudinal data pairs of GMFM ‐66 measurements (mean age 8 years 4 months [standard deviation 7 years 11 months] at start of follow‐up), Gross Motor Function Classification System levels I to V. The z‐scores for GMFM ‐66 change of a validation dataset by the new tool and the previously described method to quantify a change in GMFM ‐66 by individual effect size were highly correlated (Pearson's rank correlation coefficient 0.981 [95% confidence interval 0.979–0.984], p < 0.001) Interpretation The new reference values showed a high correlation with the previously published reference values, which were limited to an age range of 3 to 12 years. The new reference values can be applied from an age of 3 to 18 years. This facilitates the evaluation of medical treatment after a 6‐month period also for children with cerebral palsy who are older than 12 years.
Journals
2026 EN
ElBadawi Hussein · Albalkhi Nader · Al Kadhim Ibrahim
+9 more
Abstract Aim PIONEER REAL Saudi Arabia investigated real‐world clinical outcomes associated with the use of once‐daily oral semaglutide in adults with type 2 diabetes (T2D). Materials and Methods This was a 34‐ to 44‐week multicentre, prospective, open‐label study in adults with T2D, who were treatment‐naive to injectable glucose‐lowering medication and initiated oral semaglutide in routine clinical practice. The primary endpoint was change from baseline to end of study (EoS) in glycated haemoglobin (HbA1c). Secondary and exploratory endpoints included changes in body weight (BW) and waist circumference (WC) from baseline to EoS. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire‐status (DTSQs) and change (DTSQc) tools. Results In total, 192 participants initiated oral semaglutide. At baseline, mean (standard deviation) age was 51.7 (10.91) years, mean HbA1c was 8.0% (1.51) and mean BW was 90.5 kg (15.68). In total, 139 participants completed the study. Estimated mean (standard error [SE]) changes (95% confidence interval) in HbA1c and BW were −1.0%‐points (0.09; p < 0.0001) and −4.4 kg (0.51; p < 0.0001), respectively. Estimated mean (SE) change in WC was −4.3 cm (0.62; p < 0.0001). At EoS, 61.9% of participants had HbA1c levels <7%, with 21.9% and 17.1% achieving HbA1c reductions of ≥1% alongside BW reductions of ≥3% or ≥5%, respectively. Treatment satisfaction increased significantly (mean change in DTSQs +8.7 and DTSQc 14.9; both p < 0.0001). At EoS, 49.5% of participants remained on oral semaglutide, of whom 47.4% were receiving the 14.0 mg dose. Conclusions This real‐world population of adults with T2D in Saudi Arabia experienced clinically significant reductions in HbA1c and BW, increased treatment satisfaction and a favourable safety profile, consistent with previously published PIONEER REAL studies.