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This research focused on improving the drought tolerance of Dracocephalum moldavica , a plant vulnerable to water stress, by exploring the combined effects of melatonin spray and mycorrhizal fungus Glomus intraradices inoculation. The experiment was designed as a factorial randomized study to evaluate the plant’s morphological, physiological, and phytochemical responses under different drought conditions (100%, 75%, and 50% field capacity). The findings revealed that the combination of melatonin and mycorrhizal inoculation significantly improved the morphological traits of Moldavian balm under drought conditions. Under severe drought (50% field capacity), chlorophyll a and b levels increased by 26.3% and 35.5%, respectively, when both treatments were applied. Stress indicators, including electrolyte leakage and malondialdehyde content, were substantially reduced with the simultaneous application of melatonin and mycorrhizal symbiosis, indicating decreased cellular damage. Moreover, the combined treatment resulted in the highest activities of the antioxidant enzymes catalase and peroxidase, suggesting that these treatments bolster the plant’s oxidative stress defense mechanisms. Additionally, drought stress alone led to an increase in secondary metabolites like phenolic and flavonoid compounds, which were further amplified by the treatments. The study also observed significant alterations in the essential oil composition of the plant. Drought stress increased the levels of α-pinene, 1,8-cineole, and borneol, and these increases were even more pronounced with the combined treatments. Conversely, the levels of geraniol and geranial decreased under drought stress and further with treatment. Overall, this research demonstrates that melatonin and Glomus intraradices inoculation can effectively enhance drought tolerance in Dracocephalum moldavica by improving its physiological characteristics and biochemical composition.

Wolfram syndrome (WS) is a genetically disorder that affect on many organs, and neurodegenerative disorder. Although various clinical dysfunctions may have different onset times, they can collectively contribute to delays in the diagnosis of the disorder. To date, more than 200 pathogenic and likely pathogenic variant have been identified. In the present investigation, we evaluated three families with WS and reported a mutation in the WFS1. This study, we have evaluated mutation in the WFS gene in three consanguineous families including three patients with a history of young-onset DM, progressive hearing loss and optic atrophy further neurological abnormalities. Sequencing results showed a novel homozygous stop-gain variant, c.1444A > T (p.K482X), and two previously reported mutations (c.2006A > G and c.2105G > A) in exon 8 of WFS1 gene. The variant interpretation was done according to the genetic guidelines. Finally, p.K482X was determined as a novel pathogen variant. Also, analysis showed that variants in parents were heterozygous. The present survey, revealed a novel nonsense mutation in the wolframin protein, creates a frameshift which causes a premature stop codon truncating the protein in amino acid 482 residues. This mutation occurs in transmembrane domain and causes elimination of 46% of wolframin protein.

Chronic kidney disease (CKD) is closely associated with systemic inflammation. This randomized controlled trial aimed to evaluate the effects of omega‐3 fatty acids supplementation on inflammatory markers in patients with CKD undergoing hemodialysis. Eligible participants with CKD receiving hemodialysis were randomly assigned to either an intervention group or a control group. The intervention group received three capsules of omega‐3 fatty acids (3 g/day) for two months, while the control group received placebo capsules containing medium‐chain triglyceride (MCT) oil. Inflammatory markers, including C‐reactive protein (CRP) and interleukin‐6 (IL‐6), were measured both before and after the interventions. The results showed that CRP levels increased from 9.86 ± 12.64 to 11.46 ± 22.23 mg/L in the intervention group and from 5.24 ± 9.01 to 5.61 ± 7.93 mg/L in the control group (p = 0.11). Similarly, IL‐6 levels increased from 17.84 ± 14.08 to 81.82 ± 66.22 pg/mL in the intervention group and from 14.96 ± 18.41 to 56.73 ± 115.45 pg/mL in the control group (p = 0.53). No statistically significant group differences were observed after adjusting for confounders such as age, sex, body mass index (BMI), smoking, dietary intake, and pre‐existing diseases. The study findings showed that a two‐month intake of omega‐3 fatty acids supplements did not have a significant impact on reducing the levels of inflammatory markers in CKD patients undergoing hemodialysis. Larger trials with longer durations are warranted. Study Highlights What is the Current Knowledge on the Topic? ○Omega‐3 fatty acids have anti‐inflammatory properties and are reported to be potentially beneficial in reducing inflammation associated with CKD, but the evidence regarding the effectiveness of omega‐3 supplements in reducing inflammatory markers in this population remains inconsistent. What Question did this Study Address? ○What is the effect of omega‐3 fatty acids supplementation for 2 months on CRP and IL‐6 levels in patients with CKD undergoing hemodialysis? What Does This Study Add to Our Knowledge? ○Contrary to previous studies, this study found that omega‐3 fatty acids supplementation did not significantly reduce CRP or IL‐6 levels compared with placebo over 2 months and that short‐term supplementation is not sufficient to reduce systemic inflammation in hemodialysis patients. How Might this Change Clinical Pharmacology or Translational Science? ○These findings suggest that short‐term omega‐3 fatty acids supplementation may not be sufficient in reducing inflammatory markers in CKD patients undergoing hemodialysis and highlight the need for larger‐scale clinical trials with different doses and longer durations to investigate nutritional or pharmacological strategies.

Background Hearing loss (HL) is the most common sensory-neural defect worldwide and the second most common disability in Iran. This study aimed to identify the genetic cause of autosomal recessive non-syndromic hearing loss (ARNSHL) in a large Iranian family using next-generation sequencing and structural bioinformatics. Methods After a comprehensive clinical evaluation of a large family with a history of HL the GJB2 gene was sequenced, and 7 loci were screened through genetic linkage analysis. Targeted next-generation sequencing was applied following proper variant filtration, co-segregation analysis, in silico assessment, and protein modeling. The variant was checked in 50 unrelated ethnically matched controls using the HRM technique. Results The pedigree was a large autosomal recessive non-syndromic hearing loss family negative for GJB2 variants and unlinked to the selected loci. A novel missense variant, c.9455 T > G (p.L3152R), was identified in the CDH23 gene. The prediction software tools regarded it as damaging. The variant co-segregated with the phenotype in the pedigree and was absent in the controls. The variant interpretation was done based on the literatures and the American College of Medical Genetics and Genomics (ACMG) guidelines. Conclusion The present study extends the genetic variants spectrum of hereditary HL. Our analysis revealed a novel missense variant, c.9455T > G (p.L3152R), in exon 66 of the DFNB12 phenotype. Our data can be helpful for genetic counseling and preventing hereditary HL, especially in families with consanguineous marriage. Based on the ACMG.

Sensorineural hearing loss (SNHL) is a clinically and genetically heterogeneous group of disorders of the auditory system. SNHL can occur as a symptom in more than 400 syndromes, and mutations in more than 150 genes can lead to SNHL. Mutations in the GJB2 and GJB6 genes are among the most common causes of SNHL worldwide. Mutations in Cadherin 23 (CDH23) can cause Usher syndrome and/or non-syndromic hearing loss (NSHL). In this study, the Whole Exome Sequencing (WES) was used to detect the cause of hearing loss in a large consanguineous Iranian family with two patients. All family members underwent a thorough Genotype-phenotype correlation assessment and co-segregation analysis to understand the inheritance pattern within the family. The candidate variants were further confirmed by Sanger sequencing. In addition, in silico analysis was performed to predict the functional impact of the variants; the interpretation of the variants was performed in accordance with the American College of Medical Genetics (ACMG) guidelines. WES results identified two novel variants, a homozygous missense variant in CDH23 (c.2961T > G) and a heterozygous splice site variant in OTOGL that was compatible with the autosomal recessive pattern of inheritance. Bioinformatics studies confirmed the pathogenic effects of novel variants. The c.2961T > G variant was classified as likely pathogenic. The novel identified variant in the CDH23 was the cause of congenital profound progressive form of HL. Samples were not available from the second family to distinguish which variant is responsible for the molecular pathology of the disease. Further studies and functional examinations are suggested for investigating the role of OTOGL: c. 1863-1G > T in deafness.

Disorders of sexual development (DSD) are an abnormal congenital conditions associated with atypical development of the urogenital tract and external genital structures. The steroidogenic acute regulatory ( STAR ) gene, associated with congenital lipoid adrenal hyperplasia (CLAH), is included in the targeted gene panel for the DSD diagnosis. Therefore, the genetic alterations of the STAR gene and their molecular effect were examined in the CLAH patients affected with DSD. Ten different Iranian families including twelve male pseudo-hermaphroditism patients with CLAH phenotype were studied using genetic linkage screening and STAR gene sequencing in the linked families to the STAR locus. Furthermore, the structural, dynamical, and functional impacts of the variants on the STAR in silico were analyzed. Sanger sequencing showed the pathogenic variant p.A218V in STAR gene, as the first report in Iranian population. Moreover, modeling and simulation analysis were performed using tools such as radius of gyration, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and molecular docking showed that p.A218V variant affects the residues interaction in cholesterol-binding site and the proper folding of STAR through increasing H-bound and the amount of α-Helix, deceasing total flexibility and changing fluctuations in some residues, resulting in reduced steroidogenic activity of the STAR protein. The study characterized the structural and functional changes of STAR caused by pathogenic variant p.A218V. It leads to limited cholesterol-binding activity of STAR, ultimately leading to the CLAH disease. Molecular dynamics simulation of STAR variants could help explain different clinical manifestations of CLAH disease.

Hearing loss (HL) is the most common sensory-neural defect worldwide and the second most common disability in Iran. This study aimed to identify the genetic cause of autosomal recessive non-syndromic hearing loss (ARNSHL) in a large Iranian family using next-generation sequencing and structural bioinformatics. After a comprehensive clinical evaluation of a large family with a history of HL the GJB2 gene was sequenced, and 7 loci were screened through genetic linkage analysis. Targeted next-generation sequencing was applied following proper variant filtration, co-segregation analysis, in silico assessment, and protein modeling. The variant was checked in 50 unrelated ethnically matched controls using the HRM technique. The pedigree was a large autosomal recessive non-syndromic hearing loss family negative for GJB2 variants and unlinked to the selected loci. A novel missense variant, c.9455 T > G (p.L3152R), was identified in the CDH23 gene. The prediction software tools regarded it as damaging. The variant co-segregated with the phenotype in the pedigree and was absent in the controls. The variant interpretation was done based on the literatures and the American College of Medical Genetics and Genomics (ACMG) guidelines. The present study extends the genetic variants spectrum of hereditary HL. Our analysis revealed a novel missense variant, c.9455T > G (p.L3152R), in exon 66 of the DFNB12 phenotype. Our data can be helpful for genetic counseling and preventing hereditary HL, especially in families with consanguineous marriage. Based on the ACMG.

Abstract Objective Congenital adrenal hyperplasia (CAH) addresses a number of autosomal recessive disorders characterized by the enzyme defects in steroid hormones biosynthesis. The second common form of CAH is caused by mutations in the CYP11B1 gene. Here, we reveal a novel mutation in the CYP11B1 gene related to the 11βOHD phenotype. Methods and Results Sequence analysis of the CYP11B1 gene in a 19-year-old Iranian woman with the 11βOHD phenotype was performed. In silico analysis and molecular docking were done. A novel missense homozygous variant c.1351C > T (p.L451F) in the CYP11B1 gene was identified in the patient and, according to American College of Medical Genetics and Genomics criteria, was categorized as likely pathogenic. Protein docking showed destructive effects of the variant on the CYP11B1 protein-ligand interactions. Conclusion This study broadens the CYP11B1 mutation spectrum and introduces the novel p.L451F likely pathogenic variant leading to destructive effects on protein-ligand interactions. Our results provide reliable information for genetic counseling and molecular diagnostics of CAH.