👤 Hamid R Noori

This study, for the first time, sought to investigate whether the interaction between the GRS consists of three SNPs (CAV-1, CRY-1, MC4R) and fat intake is associated with inflammatory markers among Iranian overweight and obese women. This cross-sectional study was conducted with 246 overweight and obese women, aged 18-48 years. Three SNPs, including CAV-1 rs3807992, CRY-1 rs2287161, and MC4R rs17782313, were genotyped using PCR-RFLP to calculate the genetic risk score (GRS) for each participant. Dietary fat intake was measured using a validated semi-quantitative food frequency questionnaire (FFQ). C-reactive protein (CRP), interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), and Galectin-3 (Gal-3) were assessed as the primary outcomes of the study. After controlling for confounding variables, a significant interaction between high total fat intake and high GRS, compared to the reference group, was found for TGF-β level ( Consuming different types of fats can influence the interaction between GRS and inflammatory markers, suggesting further research is needed to fully understand this relationship. The online version contains supplementary material available at 10.1007/s40200-024-01542-z. Show less

Idiopathic hypereosinophilic syndrome (iHES) is a rare hematologic condition characterized by persistent, unexplained eosinophilia and organ involvement. Its diagnosis is challenging due to overlapping features with other eosinophilic and inflammatory gastrointestinal disorders. We report a case of a 44-year-old male with a history of asthma who presented with chronic epigastric pain, rectal bleeding, and significant weight loss. Initial investigations, including elevated CRP and fecal calprotectin, suggested inflammatory bowel disease, and treatment was initiated accordingly. However, symptoms persisted, and further evaluations revealed marked eosinophilic infiltration in gastric and colonic biopsies, raising suspicion for eosinophilic gastroenteritis. Repeat endoscopy showed giant gastric folds with significant eosinophilic infiltration (>120 eosinophils/HPF). Imaging demonstrated gastrointestinal wall thickening, biliary involvement, and incidental pulmonary nodules. Bone marrow biopsy revealed preserved trilineage hematopoiesis with prominent eosinophilia. Infectious, autoimmune, allergic, and neoplastic causes were systematically excluded. Cytogenetic testing was negative for PDGFRA, PDGFRB, and FGFR1 mutations, ruling out clonal eosinophilic disorders. Based on persistent peripheral eosinophilia, histologic evidence of tissue infiltration, and exclusion of secondary or clonal causes, a diagnosis of iHES was established in accordance with WHO 2024 criteria. The patient started on systemic corticosteroids, achieving partial symptom relief. Due to relapse during steroid tapering, azathioprine was added as a steroid-sparing agent. Ongoing monitoring was planned with consideration of biologic therapy for future relapses. This case illustrates the diagnostic complexity of iHES presenting with gastrointestinal involvement mimicking inflammatory bowel disease. It highlights the importance of a structured diagnostic approach, including repeated tissue evaluation and hematologic assessment, in differentiating iHES from other eosinophilic and inflammatory disorders. Show less

Replacing growth factors with a synthetic alternative molecule is an attractive opportunity to increase consistency, scalability, and cost-effectiveness of cell-based products. Herein, we describe the discovery of a chemical class of FGFR1 agonists that mimic the action of basic fibroblast growth factor (bFGF), an essential component of cell culture media. The guanylhydrazone-based molecule, TCB-32, was identified via structure-based virtual screening of the orthosteric binding site of FGFR1. It was shown to significantly increase cell proliferation by activating the FGFR1 signaling pathway like bFGF and exhibited enhanced thermostability over bFGF by retaining activity over the course of several days. After extensive structure-activity relationship studies, it was possible to increase potency and efficacy leading to three highly potent agonists. This finding has the potential to remove current bottlenecks in large-scale cell production, as required for applications such as cultivated meat or cell therapy. Show less

Protein metabolism and urea production maintain protein and amino acid homeostasis in normal status. Ammonia results from amino acid turnover and is produced by intestinal urease-positive bacteria. Ammonia must be detoxified, and the urea cycle converts ammonia into urea. CPS1 is an enzyme in the urea cycle that catalyzes ammonia and bicarbonate condensation. CPS1 deficiency presents in the neonatal period with hyperammonemia, resulting in death or neurological sequelae if patients survive. To share the experience of patients with CPS1 deficiency from Tawam Hospital and to shed light on the spectrum of variants found in those patients. A retrospective chart review was done. All patients with CPS1 deficiency admitted to Tawam Hospital from 2010 to 2023 were included. Collected data included age and ammonia level at presentation, the time needed to drop ammonia level below 100 μmol/L, acute management modality provided, long-term neurological sequelae, sequence variants, severity, and duration of hyperammonemia encephalopathy, age at last follow-up, and, if applicable, survival for at least six months. Only five patients with CPS1 deficiency over 13 years were found; two males and three females. Three patients are doing relatively well at 18 months, 7, and 9 years of age. The presented age was in the neonatal period except in one patient. One patient was found to have frameshift, resulting in a premature stop codon in the Although the presentation was different in severity, three patients are doing relatively well and approaching their developmental milestones. Thus, early recognition, prompt actions to drop high ammonia level, and good follow-up plans are emphasized. Further studies are needed to correlate the genotype-phenotype of reported variants here, which can help predict the severity of CPS1 deficiency. Show less

Autophagy is a homeostatic process that can promote cell survival or death. However, the exact role of autophagy in Clostridioides difficile infection (CDI) is still not precisely elucidated. Here, we investigate the role of distinct C. difficile ribotypes (RTs) in autophagy induction using Caco-2 cells. The expression analysis of autophagy-associated genes and related miRNAs were examined following treatment of Caco-2 cells with C. difficile after 4 and 8 h using RT-qPCR. Toxin production was assessed using enzyme-linked immunosorbent assay (ELISA). Immunofluorescence analysis was performed to detect MAP1LC3B/LC3B, followed by an autophagic flux analysis. C. difficile significantly reduced the viability of Caco-2 cells in comparison with untreated cells. Elevated levels of LC3-II and SQSTM1/p62 by C. difficile RT001 and RT084 in the presence of E64d/leupeptin confirmed the induction of autophagy activity. Similarly, the immunofluorescence analysis demonstrated that C. difficile RT001 and RT084 significantly increased the amount of LC3-positive structures in Caco-2 cells. The induction of autophagy was further demonstrated by increased levels of LC3B, ULK1, ATG12, PIK3C3/VPS34, BECN1 (beclin 1), ATG5, and ATG16L1 transcripts and reduced levels of AKT and MTOR gene expression. The expression levels of MIR21 and MIR30B, microRNAs that suppress autophagy, were differentially affected by C. difficile. In conclusion, the present work revealed that C. difficile bacteria can induce autophagy through both toxin-dependent and -independent mechanisms. Also, our results suggest the potential role of other C. difficile virulence factors in autophagy modulation using intestinal cells in vitro. Show less

Mental health and sleep quality are associated with genetics and nutrient and energy intake. The present study examined the association between ultra-processed food (UPF) intake and genetic risk score (GRS) and their interactions on mental health and sleep quality in Iranian women. A cross-sectional study was conducted on 278 overweight and obese females aged between 18 and 56 years. According to the NOVA classification system, 37 food groups and beverages were collected using a 147-item semi-quantitative food frequency questionnaire (FFQ). The blood parameters of all participants were assessed. Mini-column kit (type G; Genall; Exgene) and the PCR-RFLP method were used to extract DNA and determine gene polymorphism, respectively. Three single nucleotide polymorphisms (SNPs), including Caveolin₁ (Cav₁₎, Melanocortin4 receptor (MC4R), and cryptochrome circadian regulator 1 (CRY1), were used to calculate GRS. The individual risk allele (0, 1, 2) for each SNP was calculated using the incremental genetic model. After controlling for confounders, a significant interaction was found for depression (β = 0.026, 95% CI 0.003, 0.049, P = 0.028) and depression anxiety stress scales (DASS) score (β = 0.059, 95% CI 0.001, 0.117, P = 0.046) on the NOVA classification system and GRS. The findings of this study showed a significant interaction between GRS and the NOVA classification system on mental disorders, including depression, DASS score and stress. There was also a significant relationship between the NOVA classification system and anxiety, DASS score, sleep quality and depression. Furthermore, a partially significant association was observed between GRS and stress. Level V, cross-sectional descriptive study. Show less