SAID SHEHATA

MicroRNA-21 (miRNA-21) expression is increased in patients with kidney disease, and polysaccharides provide the structural scaffolding of the glomerular and tubular basement membranes.We investigated whether the induction of renal injury by the industrial toxic chemical thioacetamide (TAA) can dysregulate the kidney miRNA-21/SIRT1/NF-κB axis as well as the structural polysaccharide content of the kidney tissue, and whether treatment with the polyphenolic compound resveratrol can inhibit these adverse effects.Kidney injury was induced in rats by TAA (200 mg/kg) injections. The protective group of rats was pre-treated with resveratrol (20 mg/kg) prior to kidney injury and subsequently kept on resveratrol until culled.TAA intoxication caused a significant ( < 0.0001) modulation in kidney and blood levels of miRNA-21, the tissue renoprotective molecule SIRT1, NF-κB p65, kidney structural polysaccharides, the macrophage biomarker cluster of differentiation 68 (CD68), tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, hypernatremia, urea, and creatinine, as well as albuminuria that were significantly ( ≤ 0.0187) protected by resveratrol. Furthermore, a significant correlation between the miRNA-21/SIRT1/NF-κB axis, structural polysaccharides, renal fibrosis, and renal injury biomarkers was observed.These findings demonstrate an association between renal injury induced by TAA intoxication and the dysregulation of the kidney miRNA-21/SIRT1/NF-κB axis and polysaccharide levels while being protected by resveratrol.

BACKGROUND: Doxorubicin (DOX), a potent antineoplastic drug, can induce cardiotoxicity through its cardiotoxic metabolites catalyzed by CBR 3 and its accumulation in cardiac tissue via the ABCC1 transporter. Here, we investigated CBR3 and ABCC1 genetic polymorphisms affecting doxorubicin cardiotoxicity in breast cancer patients and explored the potential role of brain natriuretic peptide (BNP) as an early cardiac biomarker.

METHODS: One hundred Breast cancer patients are receiving DOX treatment. Blood samples were analyzed for CBR3 and ABCC1 gene polymorphisms and echocardiography and BNP biomarkers were used to assess cardiotoxicity at baseline and three months post-DOX treatment.

RESULTS: Following the DOX treatment, CBR3 genotypes showed significant differences in BNP levels and delta BNP ( = 0.001 and 0.014, respectively). There was a significant association between different CBR3 genotypes and BNP levels after DOX ( = 0.001) and delta BNP ( = 0.01), with AA genotypes associated with cardiotoxicity. ABCC1 was not associated significantly with cardiotoxicity ( = 0.67). There was a statistically significant difference between CBR3 genotypes and the occurrence of anemia ( = 0.023).

CONCLUSION: Detecting CBR3 genetic polymorphisms is crucial for assessing cardiotoxicity before administering DOX, and monitoring BNP levels helps early detection. CBR3 is also associated with DOX anemia.

PURPOSE: To evaluate the effectiveness and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in managing early-onset glaucoma secondary to Sturge-Weber syndrome (SWS).

DESIGN: A retrospective interventional case series.

PARTICIPANTS: Medical records of 16 patients (22 eyes) diagnosed with early-onset glaucoma secondary to SWS who underwent GATT surgery were reviewed.

METHODS: All patients underwent GATT surgery using a 5-0 or 6-0 prolene suture under general anesthesia.

MAIN OUTCOME MEASURES: The primary outcomes were intraocular pressure (IOP) reduction, complete surgical success (IOP ≤ 18 mmHg without medications), qualified surgical success (IOP ≤ 18 mmHg with medications), and postoperative complications.

RESULTS: The mean IOP decreased significantly from 25.4 ± 4.8 mmHg at baseline to 15.7 ± 4.2 mmHg at the final follow-up (P < 0.001), representing a 38.19% reduction. The mean age at the time of GATT surgery was 33.6 ± 33.9 months. The mean follow-up duration was 16.3 ± 6.4 months. Complete surgical success was achieved in 45.4% of eyes (10 out of 22), while qualified success was reached in 81.8% of eyes (18 out of 22). Despite the overall success, 18.1% of eyes (4 eyes) required additional surgical interventions during the follow-up period. These included Ahmed glaucoma valve implantation in 1 eye, trabeculectomy in 2 eyes, and transscleral diode laser cyclophotocoagulation in 1 eye. Transient hyphema was the only reported complication, resolving spontaneously within 1 week without further intervention.

CONCLUSIONS: Gonioscopy-assisted transluminal trabeculotomy appears to be a promising surgical option for managing early-onset glaucoma in patients with SWS, offering significant IOP reduction and a favorable safety profile within the limitations of our study. However, further studies with longer follow-up periods and comparative groups are necessary to confirm these findings.

FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

BACKGROUND: Data on the epidemiology and molecular characterization of feline immunodeficiency virus (FIV) in Egypt are limited. This study aimed to estimate FIV prevalence in 240 Egyptian cats during 2022–2024 using three diagnostic techniques: two point-of-care antibody detection kits (Anigen and SNAP) and one end-point PCR targeting the gene. FIV infection is defined as positivity in at least two of the three diagnostic methods or PCR alone confirmed by sequencing, Additionally, FIV-associated clinicopathological abnormalities were assessed, and, for the first time in Egypt, circulating FIV subtypes were identified through partial sequencing and phylogenetic analysis of all gene-positive samples ( = 10), along with 4 additional gene-positive samples.

RESULTS: Using our diagnostic criteria, 76 of 240 cats (31.7%) were identified as FIV-infected. Of these 76 cases, 75 were positive on both rapid kits, yielding a sensitivity of 98.7% for sequential testing with Anigen and SNAP, whereas only 10 were positive on PCR and sequencing (13.2% sensitivity). FIV-infected cats exhibited lymphopenia, thrombocytosis, hyperglobulinemia, and reduced albumin/globulin ratios. On and gene-based phylogenetic analyses, Egyptian strains did not cluster with any known FIV subtype (A-F and U-NZ) but formed a distinct, previously uncharacterized clade. The Egyptian sequences displayed low intra-group diversity (2.8–3.7%) but high divergence from all known subtypes (21–25%), with no evidence of recombination observed. Moreover, these sequences were derived from both shelter-housed and client-owned cats across three Egyptian governorates within a one-year period.

CONCLUSION: Given their genetic distinctiveness and widespread detection, we propose a novel FIV subtype, tentatively designated “X-EGY.” Its dominance and limited variability among its strains suggest it represents an ancient lineage uniquely adapted to Egyptian cats, rather than a recently emerged variant. This subtype may partly contribute to Egypt’s notably high FIV prevalence. Serological testing, utilizing two point-of-care kits in screening and confirmation steps, is the most accurate FIV diagnostic approach, outperforming molecular testing, particularly in regions where genetic data on circulating strains are scarce. Overall, the findings enhance our understanding of FIV epidemiology and diagnostic strategies and offer new insights into viral diversity and evolution.

BACKGROUND: Breast cancer remains a leading cause of morbidity worldwide, necessitating innovative and accessible interventions that address both clinical and psychosocial needs. AI-powered chatbots are increasingly used in health education due to their 24/7 availability, personalization, and interactivity. However, empirical evidence on their effectiveness in enhancing knowledge, empowerment, and attitudes in oncology settings remains limited.

AIM: This randomized controlled trial (RCT) evaluated the impact of an AI chatbot intervention on knowledge, empowerment, and attitudes toward AI among breast cancer patients.

METHODS: A two-arm, pre-post RCT was conducted with 122 women diagnosed with breast cancer at Kafr El-Sheikh University Hospital. Participants were randomly assigned to an intervention group (n = 61) receiving structured AI chatbot-based education plus standard care, or a control group (n = 61) receiving standard care alone. Data were collected using validated questionnaires assessing breast cancer and AI knowledge, attitudes toward AI, and perceived empowerment. G*Power analysis determined sample adequacy for between-group comparisons.

RESULTS: Post-intervention, the intervention group showed significantly higher knowledge (20.3 ± 2.1 vs. 17.9 ± 3.4, p <.001) and more positive attitudes (82.4 ± 7.2 vs. 72.6 ± 8.9, p <.001) compared to controls. Logistic regression indicated that knowledge gain and higher education predicted a positive AI attitude. Path analysis revealed both direct and mediated effects of knowledge on attitude via empowerment. Usage data and chatbot session logs supported high engagement.

CONCLUSION: Integrating AI chatbots into oncology nursing care significantly enhances knowledge, empowerment, and AI acceptance. These findings support chatbot integration in patient-centered digital health strategies, particularly in oncology.

CLINICAL TRIAL NUMBER: Not applicable.

TRIAL REGISTRATION: NCT06943911 (retrospectively registered on 24/4/2025).

Erectile dysfunction (ED) poses a significant challenge to male sexual health globally, prompting the exploration of alternative treatments beyond conventional pharmaceutical interventions targeting the phosphodiesterase-5 (PDE5) enzyme. This study comparatively investigates the efficacy of essential oils hydrodistilled from expanded and unexpanded flowers (EF and UF) of Citrus reticulata L. in addressing ED by targeting two key enzymes: Rho-kinase II (ROCK-II) and PDE5A1. Gas chromatography-mass spectrometry (GC/MS) was utilized to analyze the chemical composition of these oils and revealed the presence of 35 and 40 compounds in EF and UF, respectively, across various classes. Monoterpene hydrocarbons are deemed to be the dominant class, constituting 64.33% and 71.93% of the total oil composition in EF and UF, respectively. The results highlight the significant efficacy of UF, represented by their ability to modulate ROCK-II and PDE5A1 activities with IC values of 2.64 ± 0.09 and 0.42 ± 0.015 µg/mL, respectively, compared to sildenafil citrate (IC = 0.97 ± 0.03 and 0.042 ± 0.001 µg/mL). Besides, two molecular docking processes were applied to evaluate the activity of major identified volatile constituents toward PDE5A1 and ROCK-II target receptors. These findings offer valuable insights into future therapeutic strategies in ED management.

In continuous search for RANKL induced osteoclastogenesis inhibitors, twenty-six fungal isolates were obtained from ten Red Sea marine sponges collected from Egypt and the ethyl acetate fractions of their cultures' methanol extracts were assessed in RAW264 macrophages. Active fractions were profiled via LC-MS/MS, followed by untargeted molecular networking, leading to the tentative identification of eight unreported compounds (1, A2, C1, C2, C4-C7), and thirteen known compounds. The two active fungi were identified and deposited in GenBank with accession numbers PQ423742 and PQ423748 for Aspergillus flavus and Cladosporium colombiae, respectively. Bioassay-guided isolation afforded two bisphenol diglycidic ethers, 1 and 2, and two diketopiperazines, 3 and 4 from A. flavus, while C. colombiae yielded cinnamic acid (5), two diketopiperazines (6 and 7), and altenuene (8). Structures were elucidated by NMR and mass spectroscopic analyses, which revealed 1 to be isolated for the first time from natural sources. Isolated compounds were biologically evaluated. Only 1 and 8 inhibited RANKL-induced formation of mature multinucleated osteoclasts with IC 57.14 and 38.35 µM, respectively, without cytotoxicity against RAW264 macrophages. The ADMET properties for 1 and 8 were predicated using SwissADME and pkCMS platforms. 8 showed superior solubility and lower toxicity than compound 1.

Endoplasmic reticulum (ER) stress and misfolded proteins accumulation are recognized as central factors in the development of psychiatric disorders. This study evaluated the potential therapeutic effect of fluvoxamine, a potent sigma-1 receptor agonist in alleviating protein misfolding and the subsequent ER stress in ketamine-induced model of schizophrenia. NE100 hydrochloride, a sigma-1 receptor blocker, was used to investigate the role of this receptor in fluvoxamine-mediated effects. Rat model of schizophrenia was induced by intraperitoneal administration of ketamine (30 mg/kg/day) for 5 consecutive days. Then, rats were treated with fluvoxamine (30 mg/kg/day, p.o), with or without NE100 (1 mg/kg/day, i.p), for 14 days. Fluvoxamine improved the learning abilities, cognitive flexibility, and sociability functions of ketamine-subjected rats as evidenced in Morris water maze and three-chamber social interaction tests. It mitigated ketamine-induced inhibition of nNOS/PSD-95/NMDAR signaling pathway, thus augmented the function of parvalbumin-GABAergic neurons as indicated by increasing the prefrontal cortical levels of parvalbumin and GAD67. Fluvoxamine also attenuated the prefrontal cortical production of unfolded protein response markers, namely, IRE-1, PERK, and ATF-6, highlighting its ability to alleviate ER stress. Further, it exerted anti-apoptotic and anti-inflammatory effects as shown by lowering Iba-1, tumor necrosis factor-α (TNF-α), Bax, and caspase-12 levels contrary to elevating Bcl-2. Additionally, it attenuated the histopathological alterations in prefrontal cortical neurons. Noteworthy, the co-administration of NE100 reduced the advantageous effects of fluvoxamine, indicating the involvement of sigma-1 receptor in mediating the observed antipsychotic effects. Thus, sigma-1-mediated signaling pathways could be therapeutic targets for preventing or slowing schizophrenia progression.

The rising incidence of breast cancer (BC) among Egyptian females with a mortality rate of 11% and younger age at diagnosis implied the study of the interplay of BRCA gene variants with other BC risk factors. The study enrolled 500 BC Egyptian females with a mean age of 47.29 ± 13.26 years for whom BRCA1/2 testing was offered. A history of BC and/or other related cancer was recorded for all patients. Peripheral blood samples were obtained for genomic DNA extraction in view of germline BRCA gene testing on the MiSeq platform. A positive family history was reported in 352 patients (70.4%). Patients with hormone receptor-positive (HR+) BC constituted 195 cases (39%) cases, while 305 patients (61%) had hormone receptor-negative (HR-) BC. Among the HR- group, 268 patients (53%) had triple-negative BC (TNBC), and 37 patients had low estrogen receptor (ER) (1-10%) and/ or low progesterone receptor (PR) expression with HER2 negative status. Patients with HER2-positive BC were excluded from the enrollment and directed to specific targeted therapy. Variants were classified according to the American College of Medical Genetics (ACMG) and the Association for Molecular Pathology (AMP) criteria. Carriers of gBRCA1/2 PVs/LPVs were 58 patients (11.6%) of whom 34 (6.8%) had BRCA1 PVs/LPVs and 24 (4.8%) had BRCA2 PVs/LPVs. Patients with TNBC demonstrated a higher rate of gBRCA1/2 PVs/LPVs (17.5%). We recorded 55 PVs/LPVs in both genes, 44 single nucleotide variants (SNVs), and 11 copy number variations (CNVs). Three novel gBRCA1 LPVs; c.2791del, c.361G>T and c.4431dup and two novel gBRCA2 LPVs; gBRCA2 c.3139del and c.5690 dup were identified. Variants of uncertain significance (VUS) were found in 22 patients, of whom 13 (59%) had a positive family history of breast/ovarian cancer. Genomic testing for BRCA1/2 status as part of a routine BC diagnostic workup contributes to comprehensive BC risk assessment.Trial registration: Egyptian National Cancer Institute IRB approval number: 2301-305-051. Date of registration: 24th Jan 2023.

HMG-CoA reductase inhibitors, statins, are extensively used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic disorders. However, one of the common side effects of statin therapy is a mild elevation in liver aminotransferases, observed in less than 3% of patients. Atorvastatin and simvastatin, in particular, are most frequently associated with statin-induced liver injury, leading to treatment discontinuation. Recent research has highlighted the antioxidant and anti-inflammatory properties of glucagon-like peptide-1 receptor (GLP-1R) activation in protecting against liver injury. Nonetheless, the potential protective effects of liraglutide (LIRA), a GLP-1R agonist, against atorvastatin (ATO)-induced liver dysfunction have not been fully elucidated. In this context, the present study aimed to investigate the protective role of LIRA in mitigating ATO-induced liver injury in rats, offering new insights into managing statin-associated hepatotoxicity. Indeed, LIRA treatment improved liver function enzymes and attenuated histopathological alterations. LIRA treatment enhanced antioxidant defenses by increasing Nrf2 content and superoxide dismutase (SOD) activity, while reducing NADPH oxidase. Additionally, LIRA suppressed inflammation by downregulating the HMGB1/TLR-4/RAGE axis and inhibiting the protein expression of pY323-MAPK p38 and pS635-NFκB p65 content resulting in decreased proinflammatory cytokines (TNF-α and IL-1β). Furthermore, LIRA upregulated GLP-1R gene expression and promoted autophagic influx via the activation of the pS473-Akt/pS486-AMPK/pS758-ULK1/Beclin-1 signaling cascade, along with inhibiting apoptosis by reducing caspase-3 content. In conclusion, LIRA attenuated ATO-induced oxidative stress and inflammation via activation of the Nrf-2/SOD cascade and inhibition of the HMGB1/TLR-4/RAGE /MAPK p38/NFκB p65 axis. In parallel, LIRA stimulated autophagy via the AMPK/ULK1/Beclin-1 axis and suppressed apoptosis, thus restoring the balance between autophagy and apoptosis.

Multiple sclerosis (MS) is devastating motor disorders accompanied by cognitive impairments. Dalfampridine (Dal), was approved for treating MS via blocking voltage-gated potassium channel (Kv). Kv1.3 is one of Dals' targets that showed insults to cognitive function in preclinical and clinical cases. Yet, there is no study that has assessed the potentiality of Dal on Kv1.3-induced cognitive impairment in MS. Thus, the aim of the present study is to reveal the procognitive influence of Dal in the MS animal model. Mice were randomly assigned into four groups. Saline was administered to group 1, conversely groups 2, 3, and 4 received 2 shots of rat spinal cord emulsified with complete Freund's adjuvant. Group 3 received Dal (10 μg/mouse; p. o), while group 4 received Wortmannin (0.1 μg/mouse; i. c.v), a selective phosphoinositide 3-kinases (PI3K) inhibitor, before Dal administration. After 14 days, Dal alleviated motor deficits in the open field arena and rotarod with cognitive restoration in the novel object recognition task. These were accompanied by the reversal of hippocampal neuronal loss and demyelination in corpus callosum. Additionally, Dal inhibited Kv1.3 that enhanced survival signaling, viz; PI3K/Akt. Such activation abates neuroinflammatory markers, glycogen synthase kinase-3 beta (GSK-3β) and nuclear factor-κB levels with subsequent enhancement of BDNF. All these amendments were reversed by Wortmannin pre-administration. In conclusion, this study declares that blockade of Kv1.3 and modulation of PI3K/Akt/GSK-3β/BDNF axis with Dal could be proposed as a promising neuroprotective and memory-enhancing treatment in MS.

Oral cancer, particularly oral squamous cell carcinoma (OSCC), ranks as the sixth most prevalent cancer globally, with rates of occurrence on the rise. The diagnosis of OSCC primarily depends on histopathological images (HIs), but this method can be time-intensive, expensive, and reliant on specialized expertise. Manual diagnosis often leads to inaccuracies and inconsistencies, highlighting the urgent need for automated and dependable diagnostic solutions to enhance early detection and treatment success. This research introduces a deep learning (DL) approach utilizing EfficientNet-B3, complemented by learning rate tuning (LRT), to identify OSCC from histopathological images. The model is designed to automatically modify the learning rate based on the accuracy and loss during training, which improves its overall performance. When evaluated using the oral tumor dataset from the multi-cancer dataset, the model demonstrated impressive results, achieving an accuracy of 99.84% and a specificity of 99.92%, along with other strong performance metrics. These findings indicate its potential to simplify the diagnostic process, lower costs, and enhance patient outcomes in clinical settings.

Ferroptosis is critical in progressing and exacerbating rheumatoid arthritis (RA) and other inflammatory joint diseases. Inhibition of the P2Y12 receptors reduced iron overload in macrophages displaying an anti-inflammatory response. Herein, the ameliorative effect of ticagrelor, a reversible P2Y12 inhibitor, against adjuvant-induced arthritis (AIA) in rats was investigated, with a special emphasis on the possible modulation of some inflammatory signals linked to ferroptosis. Particularly, correlation analyses were conducted between nod-like receptor protein 3 (NLRP3) and all assessed parameters. Four groups of rats were assigned: Control group, AIA group (0.1 ml intradermal injection of complete Freund's adjuvant), Ticagrelor group (30 mg/kg, p.o.), and Ticagrelor + AIA group. Ticagrelor exhibited an anti-arthritic effect, evidenced by significant improvements in both macroscopic and histopathological alterations. It effectively inhibited ferroptosis, indicated by a marked upregulation of the ferroptotic inhibitors, solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) to reach 9.80, 2.20, and 8.49-folds (p < 0.0001), along with a notable reduction in the ferroptotic promoters, P53, acyl-CoA synthetase long-chain family member 4 (ACSL4) and arachidonic acid 15-lipoxygenase-1 (ALOX15) by 89.46%, 41.45% and 49.85% (p < 0.0001). It reduced TNF-α and various chemokines (RANTES, MIP-1α, eotaxin-3) to suppress matrix metalloproteinases expression. Furthermore, ticagrelor decreased NLRP3 expression by 48.63% (p < 0.0001) to pinpoint its anti-inflammatory effect. Overall, amending the P53/SLC7A11/ALOX15 axis by ticagrelor mediated its anti-inflammatory and anti-ferroptotic effects. These findings provide preliminary experimental evidences for further investigating the potential impacts of ticagrelor as a treatment for RA.

To evaluate the diagnostic yield of prenatal exome sequencing (pES) in fetuses with structural anomalies detected by prenatal ultrasound in a consanguineous population. This was a prospective study of 244 anomalous fetuses from unrelated consanguineous Egyptian families. Detailed phenotyping was performed throughout pregnancy and postnatally, and pES data analysis was conducted. Genetic variants were prioritized based on the correlation of their corresponding human phenotype ontology terms with the ultrasound findings. Analyses were carried out to determine the diagnostic efficiency of pES and its correlation to the organ systems involved. The largest clinical category of fetuses referred for pES was those manifesting multisystem anomalies (104/244, 42.6%). pES provided a definitive diagnosis explaining the fetal anomalies in 47.1% (115/244) of the cases, with the identification of 122 pathogenic or likely pathogenic variants completely fitting with the phenotype. Variants of uncertain significance associated with the fetal phenotypes were detected in 84 fetuses (34%), while 18.44% (45/244) had negative results. Positive consanguinity is associated with a high diagnostic yield of ES. The novel variants and new fetal manifestations, described in our cohort, further expand the mutational and phenotypic spectrum of a wide variety of genetic disorders presenting with congenital malformations.

Optimal nutrition during infancy and early childhood is crucial for promoting lifelong health and well-being. Complementary feeding is a crucial phase in the nutritional journey of growing babies, as their nutritional requirements begin to surpass those provided by breast milk at approximately 4-6 months of age. While a nutritional gap, notably iron deficiency, is prevalent in the Middle East and North Africa (MENA) region, optimal complementary feeding practices and fortified food items such as iron-fortified infant cereals can help bridge this gap and achieve nutritional targets. Healthcare professionals play a pivotal role in providing expert guidance and support to parents during this crucial stage of development. However, the MENA region, with its diverse populations and varied weaning practices in different cultures, lacks unified guidelines specific to the region. This consensus is intended to serve as a foundation for pediatricians and primary care physicians in the MENA region to advise parents and caregivers about optimal complementary feeding practices.

Optimal nutrition during infancy and early childhood is crucial for promoting lifelong health and well-being. Complementary feeding is a crucial phase in the nutritional journey of growing babies, as their nutritional requirements begin to surpass those provided by breast milk at approximately 4-6 months of age. While a nutritional gap, notably iron deficiency, is prevalent in the Middle East and North Africa (MENA) region, optimal complementary feeding practices and fortified food items such as iron-fortified infant cereals can help bridge this gap and achieve nutritional targets. Healthcare professionals play a pivotal role in providing expert guidance and support to parents during this crucial stage of development. However, the MENA region, with its diverse populations and varied weaning practices in different cultures, lacks unified guidelines specific to the region. This consensus is intended to serve as a foundation for pediatricians and primary care physicians in the MENA region to advise parents and caregivers about optimal complementary feeding practices.

Genetic causes of steroid-resistant-nephrotic-syndrome (SRNS) represent a rapidly growing number of monogenic diseases. The reported diagnostic yield of various studies applying genetic panels and exome-sequencing to diagnose SRNS is usually < 30%. We performed genome-sequencing in a cohort of Egyptian SRNS patients. We recruited 47 SRNS patients belonging to 41 unrelated families [28 males/19 females; median (range): 6 (0.5-22 years)]. We established a pipeline for genome sequencing, bioinformatics analysis, variant curation and protein modeling at the Egypt Center for Research and Regenerative Medicine (ECRRM). Disease-causing variants were detected in 27/47 patients (57.4%) belonging to 23/41 families (56.1%), including nine novel variants in NPHS1, NPHS2, COL4A3, MYO1E, NUP93, PLCE1, PODXL, SMARCAL1 and WT1. Novel variants were confirmed by Sanger sequencing and were segregated in families of affected patients. NPHS2 was the most common causative gene in 8/23 (34.8%) of confirmed families, followed by NPHS1, WT1, and SMARCAL1 in 2/23 families (8.7%) each. All detected missense variants were evaluated through protein modeling and were predicted deleterious. Our study expanded the spectrum of SRNS disease-causing variants and revealed a monogenic cause in 56.1% of investigated families. In our cohort, no deep intronic or regulatory variants were detected by genome-sequencing. Pursuing genetic diagnosis in SRNS patients is crucial to inform clinical decision making, genetic counseling, transplantation strategy and prenatal diagnosis thus improving clinical outcome of affected patients.

Non-alcoholic fatty liver disease (NAFLD) is a liver pathology concomitant with metabolic disarrangement. This study assessed the therapeutic impacts of delphinidin, an anthocyanin, or α-amyrin, a pentacyclic triterpenoid, on NAFLD in rats and the underlying mechanisms involved. NAFLD was established by feeding a high-fat diet (HFD) for 10 weeks, either alone or in combination with delphinidin (40 mg/kg, oral) or α-amyrin (20 mg/kg, oral). Delphinidin or α-amyrin ameliorated the metabolic and histopathological perturbations induced by HFD. These compounds markedly attenuated NAFLD-induced hepatic steatosis, as evidenced by a substantial decrease in body weight, insulin resistance, and liver and adipose tissue indices. Alongside normalization of the atherogenic index, both improved HFD-mediated abnormalities in serum lipids, liver enzymes, leptin, and ghrelin levels. Moreover, their intervention activated the NFE2 like bZIP transcription factor 2 and heme oxygenase 1 pathways and abrogated HFD-triggered activation of mitogen-activated protein kinase 1 signaling. These remedies inhibited hepatic apoptosis and modulated the gene expression of lipogenic enzymes. Furthermore, histological analysis corroborated the suppression of lipid accumulation and amelioration of hepatic architecture in the treated rats. Our findings highlight the hepatoprotective value of delphinidin or α-amyrin against NAFLD and related metabolic diseases through their insulin-sensitizing, anti-inflammatory, antioxidant, and antiapoptotic effects.

Wilson's disease is a rare inherited disorder causing copper accumulation, which may adversely affect bone health in children. To assess bone mineral density and the prevalence of osteopenia and osteoporosis in pediatric Wilson's disease patients using DEXA. A cross-sectional study was conducted on 15 children with confirmed Wilson's disease. Bone mineral density was assessed using dual-energy X-ray absorptiometry (DEXA), and clinical, biochemical, and treatment-related variables were analyzed. The mean age was 10 ± 3.6 years; 53% were female. DEXA revealed bone disease in 60%: mild osteopenia (13%), moderate (27%), and osteoporosis (20%). Bone disease did not correlate with treatment duration, urinary copper, calcium, phosphorus, or alkaline phosphatase. However, serum albumin positively correlated with bone density ( = .018). Bone disease is frequent and often subclinical in pediatric Wilson's disease. DEXA is a useful tool for early detection. Larger studies are needed to evaluate the effects of treatment and micronutrient status on bone health.

Wilson's disease is a rare inherited disorder causing copper accumulation, which may adversely affect bone health in children. To assess bone mineral density and the prevalence of osteopenia and osteoporosis in pediatric Wilson's disease patients using DEXA. A cross-sectional study was conducted on 15 children with confirmed Wilson's disease. Bone mineral density was assessed using dual-energy X-ray absorptiometry (DEXA), and clinical, biochemical, and treatment-related variables were analyzed. The mean age was 10 ± 3.6 years; 53% were female. DEXA revealed bone disease in 60%: mild osteopenia (13%), moderate (27%), and osteoporosis (20%). Bone disease did not correlate with treatment duration, urinary copper, calcium, phosphorus, or alkaline phosphatase. However, serum albumin positively correlated with bone density ( = .018). Bone disease is frequent and often subclinical in pediatric Wilson's disease. DEXA is a useful tool for early detection. Larger studies are needed to evaluate the effects of treatment and micronutrient status on bone health.

Wilson's disease is a rare inherited disorder causing copper accumulation, which may adversely affect bone health in children. To assess bone mineral density and the prevalence of osteopenia and osteoporosis in pediatric Wilson's disease patients using DEXA. A cross-sectional study was conducted on 15 children with confirmed Wilson's disease. Bone mineral density was assessed using dual-energy X-ray absorptiometry (DEXA), and clinical, biochemical, and treatment-related variables were analyzed. The mean age was 10 ± 3.6 years; 53% were female. DEXA revealed bone disease in 60%: mild osteopenia (13%), moderate (27%), and osteoporosis (20%). Bone disease did not correlate with treatment duration, urinary copper, calcium, phosphorus, or alkaline phosphatase. However, serum albumin positively correlated with bone density ( = .018). Bone disease is frequent and often subclinical in pediatric Wilson's disease. DEXA is a useful tool for early detection. Larger studies are needed to evaluate the effects of treatment and micronutrient status on bone health.

OBJECTIVE: To investigate netrin-1 (NT-1) and neuron-specific enolase (NSE) in the umbilical cord as biomarkers in HIE stage II/III.

MATERIALS AND METHODS: We included 100 infants with HIE stage II/III and 100 controls. Cord samples were taken to determine the levels of NT-1 and NSE.

RESULTS: The HIE group showed significantly higher NT-1 (343.3 ± 100.6 pg/mL) and NSE (55.17 ± 13.4 ng/mL;  = .037,  = .007, respectively) than the control group, which had NT-1 (268.1 ± 79.3 pg/mL) and NSE (31.3 ± 19.5 ng/mL). The cut-off values for NT-1 and NSE were 289.3 pg/mL and 31.9 ng/mL, respectively. NT-1 had a sensitivity of 92%, a specificity of 100%, a positive predictive value (PPV) of 94%, and a negative predictive value (NPV) of 100%. The sensitivity, specificity, PPV, and NPV for NSE were all 100%.

CONCLUSION: NT-1 and NSE can be reliable biomarkers for predicting HIE stage II/III.

OBJECTIVE: To investigate netrin-1 (NT-1) and neuron-specific enolase (NSE) in the umbilical cord as biomarkers in HIE stage II/III.

MATERIALS AND METHODS: We included 100 infants with HIE stage II/III and 100 controls. Cord samples were taken to determine the levels of NT-1 and NSE.

RESULTS: The HIE group showed significantly higher NT-1 (343.3 ± 100.6 pg/mL) and NSE (55.17 ± 13.4 ng/mL;  = .037,  = .007, respectively) than the control group, which had NT-1 (268.1 ± 79.3 pg/mL) and NSE (31.3 ± 19.5 ng/mL). The cut-off values for NT-1 and NSE were 289.3 pg/mL and 31.9 ng/mL, respectively. NT-1 had a sensitivity of 92%, a specificity of 100%, a positive predictive value (PPV) of 94%, and a negative predictive value (NPV) of 100%. The sensitivity, specificity, PPV, and NPV for NSE were all 100%.

CONCLUSION: NT-1 and NSE can be reliable biomarkers for predicting HIE stage II/III.

RATIONALE: Umbilical vein catheterization (UVC) is a common procedure in neonatal intensive care units (NICU) but carries risks of severe complications such as portal vein thrombosis (PVT). Extrahepatic biliary atresia (EHBA), a leading cause of neonatal cholestasis, often progresses to end-stage liver disease. This case report discusses the rare coexistence of PVT and EHBA in a 3-month-old infant, highlighting the critical need for timely diagnosis and intervention.

PATIENT CONCERNS: A 3-month-old female presented with jaundice, dark-colored urine, and clay-colored stools. She had a history of NICU admission for neonatal sepsis during which a UVC was inserted.

DIAGNOSES: Physical examination revealed jaundice and hepatosplenomegaly. Abdominal ultrasonography identified hepatosplenomegaly, mild ascites, and portal cavernoma. A liver biopsy confirmed a diagnosis of EHBA.

INTERVENTIONS: The patient underwent Kasai portoenterostomy. Postoperatively, she developed complications including ascites, systemic hypertension, and hyperammonemia. Initial improvements were observed with decreased bilirubin levels.

OUTCOMES: Despite initial stabilization, the patient's condition deteriorated, and she succumbed on day 15 postoperation.

LESSONS: This case underscores the significant risks of PVT associated with UVC and the importance of monitoring NICU graduates for early detection of complications. The early onset of portal hypertension and esophageal varices in this case challenges existing beliefs about EHBA's clinical progression. Greater awareness and routine follow-up imaging are essential to improve outcomes in similar scenarios.

RATIONALE: Umbilical vein catheterization (UVC) is a common procedure in neonatal intensive care units (NICU) but carries risks of severe complications such as portal vein thrombosis (PVT). Extrahepatic biliary atresia (EHBA), a leading cause of neonatal cholestasis, often progresses to end-stage liver disease. This case report discusses the rare coexistence of PVT and EHBA in a 3-month-old infant, highlighting the critical need for timely diagnosis and intervention.

PATIENT CONCERNS: A 3-month-old female presented with jaundice, dark-colored urine, and clay-colored stools. She had a history of NICU admission for neonatal sepsis during which a UVC was inserted.

DIAGNOSES: Physical examination revealed jaundice and hepatosplenomegaly. Abdominal ultrasonography identified hepatosplenomegaly, mild ascites, and portal cavernoma. A liver biopsy confirmed a diagnosis of EHBA.

INTERVENTIONS: The patient underwent Kasai portoenterostomy. Postoperatively, she developed complications including ascites, systemic hypertension, and hyperammonemia. Initial improvements were observed with decreased bilirubin levels.

OUTCOMES: Despite initial stabilization, the patient's condition deteriorated, and she succumbed on day 15 postoperation.

LESSONS: This case underscores the significant risks of PVT associated with UVC and the importance of monitoring NICU graduates for early detection of complications. The early onset of portal hypertension and esophageal varices in this case challenges existing beliefs about EHBA's clinical progression. Greater awareness and routine follow-up imaging are essential to improve outcomes in similar scenarios.