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Magnesium is vital for numerous cellular processes and has demonstrated therapeutic potential in various physiological and pathological contexts. Colorectal cancer remains a major cause of cancer-related mortality worldwide. This study evaluates the effects of a multi-component magnesium supplement on human colon fibroblasts (CCD-18Co) and colon cancer cells (HCT-116). CCD-18Co and HCT-116 cells were treated with 2.5 μL dose of the Kiperin multi-component magnesium supplement. Cell viability was assessed via cell counting, and migration was analyzed using wound healing assays. Oxidative stress was evaluated by measuring total oxidant status (TOS) and total antioxidant status (TAS). Gene expression levels of VDR and TNFα genes were measured by Real-Time PCR. Magnesium complex supplementation significantly reduced HCT-116 viability ( p  < 0.001) while enhancing CCD-18Co proliferation ( p  < 0.01). Cell migration increased in CCD-18Co cells at 18 h ( p  < 0.05), while HCT-116 migration decreased at 6 h ( p  < 0.05) and increased at 18 h. TOS levels were significantly decreased in both cell lines, indicating reduced oxidative stress. Additionally, magnesium supplementation upregulated VDR expression and downregulated TNFα in CCD-18Co cells. Similarly, in HCT-116 colon cancer cells, VDR expression was significantly increased, whereas TNFα expression showed no statistically significant change. Magnesium supplement may exert selective effects by inhibiting colon cancer cell survival while supporting proliferation and anti-inflammatory signaling in normal colon cells. These findings highlight its potential utility in colon cancer prevention and gut health.

In genetic disease assessment centers, DNA sequencing can produce results irrelevant to the genetic examination’s purpose. The American College of Medical Genetics and Genomics (ACMG) recommends evaluating and reporting 81 genes discovered using clinical genomic sequencing. While population studies on large cohorts can provide statistics on the prevalence of secondary findings (SFs), no studies have been published yet on large cohorts in Turkiye. We investigated ACMG SF by evaluating clinical exome sequencing data in 1600 individuals from different regions in Turkiye. We detected SF variants reported in ClinVar in 86 individuals (5.375%). Of the SFs, 30% were cardiovascular, 26% were cancer, 16% were neonatal metabolic disorders, and 28% were variants associated with various genetic diseases. In addition, we identified 212 different variants in 226 individuals and 45 different genes, which were not reported in ClinVar. When our results are compared with the Turkish National Genome and Bioinformatics Project database and studies in the literature, the studies vary in terms of participant characteristics, sequencing techniques, and versions of the ACMG SF list. Our findings highlight the importance of expanding and tailoring SF reporting guidelines in populations with high consanguinity and limited cohort-based data.

Background/Objectives: Kiperin Postbiotics, defined as non-viable metabolic products derived from probiotics, have gained attention as potential modulators of cellular responses involved in tissue repair. This study aimed to evaluate the effects of a postbiotic supplement (PS)—composed of inactivated strains of Escherichia coli, Lacticaseibacillus rhamnosus, and Lactiplantibacillus plantarum—on fibroblast function, particularly in the context of bacterial secretomes from common pathogenic strains. Methods: Human fibroblast cell lines (HFF-1 and CCD-18Co) were treated with cell-free supernatants (CFS) from E. coli ATCC 25922, Staphylococcus aureus ATCC 29213, and Enterococcus faecalis ATCC 29212, either alone or in combination with the PS. Assessments included cell count, migration (via scratch assay), oxidative stress levels, and expression of immune-related genes (IL-6, IL-10, TNF-α, DRD4). Results: CFS from E. faecalis significantly increased fibroblast counts, whereas E. coli and S. aureus CFS reduced cell counts and elevated oxidative stress. Co-treatment with PS reversed these effects in a strain-dependent manner by lowering oxidative stress and partially restoring cell proliferation. Scratch assays demonstrated enhanced migration in PS-treated fibroblasts. Gene expression analyses revealed no statistically significant changes, though variable trends were observed across treatment groups. Conclusions: PS may mitigate the harmful effects of certain bacterial secretomes while preserving or enhancing beneficial ones. Its ability to reduce oxidative stress and promote fibroblast proliferation and migration suggests a potential pro-regenerative role in vitro. Although gene expression changes were limited, the results offer initial insights into the underlying molecular responses influenced by postbiotic supplementation.

Background: Carvacrol, a natural phenolic monoterpenoid, has been suggested to exert anticancer effects; however, its underlying mechanisms in breast cancer (BC) remain incompletely defined. Methods: MCF-7 (HR+) and MDA-MB-231 (TNBC) BC cell lines were treated with carvacrol at various concentrations. Cell viability was assessed using CVDK8 kit, while migration was evaluated by wound healing assays. Apoptosis was determined using Annexin V-FITC Kit, and ROS levels were measured by DCFH-DA assay. Flow cytometry was used for CD44/CD133 cancer stem cells markers analysis, and genes expression were quantified using qPCR. Results: Carvacrol significantly inhibited cell proliferation, and migration in both HR+ and TNBC cells. Additionally, carvacrol increased the BAX/BCL2 ratio, induced apoptosis, and decreased ROS levels, with greater antioxidant activity observed in MCF-7 cells. Moreover, carvacrol suppressed CD44+ levels, whereas CD133+ levels were not affected. Gene expression analysis revealed subtype-specific effects where ABCG2 was upregulated in MCF-7 cells but downregulated in MDA-MB-231 cells, while NFKB1 expression increased in both lines. Conclusions: Carvacrol exerts multitargeted anticancer effects in BC by promoting apoptosis, reducing ROS, and suppressing CD44+, with distinct subtype-specific responses. These findings highlight carvacrol as a promising natural therapeutic compound for BC treatment; however, further in vivo studies and clinical investigations are required to validate its translational potential.

Neurodevelopmental disorders (NDDs) with ataxia are genetically heterogeneous and remain a diagnostic challenge. Recent advances in genomic technologies have facilitated the identification of rare, potentially causative variants in genes not traditionally associated with classic NDD phenotypes. The DNAH14 gene, encoding a dynein axonemal heavy chain involved in ciliary motility, has recently emerged as a novel candidate in neurological syndromes. Here, we report two Turkish siblings presenting with late-onset balance disorder, progressive ataxia, and cognitive impairment. Initial genetic analysis revealed that both siblings also harbor FXN GAA repeat expansions consistent with pathogenic Friedreich’s ataxia (FRDA). To elucidate the molecular basis of the patients’ cognitive impairment, whole-exome sequencing was performed. This analysis identified a novel homozygous frameshift variant in the DNAH14 gene, located within the conserved linker domain upstream of the motor core, which is critical for ATP hydrolysis and microtubule interactions. The variant is absent from population databases, predicted to be deleterious by multiple in silico algorithms, and segregates in the family in a manner consistent with autosomal recessive inheritance. The coexistence of FRDA expansions and a truncating DNAH14 variant suggests a potential dual genetic contribution to the observed phenotype, in which FRDA-associated pathology likely underlies the ataxia, while DNAH14 disruption may contribute to additional neurodevelopmental features. This is the first report describing the co-occurrence of FRDA and a homozygous truncating DNAH14 variant in the same individuals, broadening our understanding of overlapping neurogenetic mechanisms. Our findings expand the phenotypic spectrum of DNAH14-related disorders and highlight the importance of considering multilocus pathogenic variants in patients with complex or atypical ataxia presentations.

Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder characterized by cerebellar ataxia, congenital cataracts, developmental delay, hypotonia, and progressive myopathy. Most reported cases are linked to pathogenic variants in , a gene encoding a co-chaperone essential for protein folding in the endoplasmic reticulum. Here, we present a comprehensive case study of a Turkish pediatric patient diagnosed with MSS, supported by genetic, bioinformatic, and structural modeling analyses. Whole-exome sequencing revealed a homozygous splice-site variant ( c.453+1G>T), confirmed by Sanger sequencing and segregation analysis. In silico annotation using Genomize, InterVar, Franklin, VarSome, ClinVar, OMIM, and PubMed classified the variant as pathogenic according to ACMG guidelines. Structural modeling by Phyre2 and I-TASSER demonstrated that the variant abolishes the intron 5 donor site, leading to truncation of the wild-type 461-amino-acid protein into a shortened ~189-amino-acid polypeptide. This truncation results in the loss of critical Armadillo (ARM) repeats required for HSPA5 interaction, explaining the observed instability and impaired chaperone function. Clinically, the patient presented with congenital cataracts, ataxia, developmental delay, and progressive muscle weakness, consistent with previously reported MSS cases. Comparison with the literature confirmed that splice-site variants frequently correlate with severe phenotypes, including early-onset ataxia and cataracts. This report highlights the importance of integrating genomic, structural, and clinical data to better understand genotype-phenotype correlations in MSS. Our findings expand the mutational spectrum of , reinforce the role of splicing defects in disease pathogenesis, and emphasize the necessity of comprehensive molecular diagnostics for rare neurogenetic syndromes.

Chronic stress is known to impair emotional regulation and adaptive behavioral responses through neuroinflammatory activation, oxidative imbalance, and dysregulation of neuroplasticity-related genes. Kiperin Mind Focus, a nootropic nutraceutical containing L-theanine, citicoline, phosphatidylserine, , caffeine, and Lion's Mane mushroom extract has been formulated to support stress resilience, mood regulation and neural health. This study aimed to investigate the neuroprotective and neuroregulatory effects of the combined formulation on behavioral, biochemical, histopathological, and molecular parameters in rats exposed to chronic unpredictable mild stress (CUMS). Thirty-two adult male Wistar rats were randomized into four groups ( = 8): Control, Stress, Kiperin Mind Focus (MF), and Stress + Mind Focus (SMF). CUMS was applied for 45 days, and the combined formulation was administered by oral gavage (130 mg/kg/day). Behavioral outcomes were evaluated using the sucrose preference (SPT), open field (OFT), elevated plus maze (EPM), and forced swim (FST) tests. Serum and tissue cytokine levels ( β -α) and oxidative stress index (TOS/TAS ratio) were measured. Hippocampal and prefrontal gene expression of , and was assessed via qPCR, and histopathological changes were semi-quantitatively scored. Chronic stress induced anhedonia, anxiety-like behavior, and behavioral despair, accompanied by elevated proinflammatory cytokines, oxidative imbalance, and neuronal degeneration in the hippocampus and prefrontal cortex. The supplementation significantly improved SPT, OFT, EPM, and FST performance, normalized cytokine and oxidative parameters, and reduced neuronal injury scores. At the molecular level, supplementation attenuated stress-induced upregulation of , , and while maintaining neurotrophic ( , ) and GABAergic ( ) expression near control levels. Kiperin Mind Focus exerted robust neuroprotective, anti-inflammatory, and antioxidant effects under chronic stress, restoring molecular homeostasis and stabilizing stress-related behavioral outcomes. These findings support its role as a stress-buffering and mood-stabilizing supplement, that promotes emotional regulation and adaptive exploratory behavior under prolonged stress conditions.

Background: Inherited kidney diseases represent a genetically and clinically heterogeneous group of disorders affecting both pediatric and adult populations. Advances in next-generation sequencing (NGS) have improved diagnostic precision; however, genotype–phenotype correlations and diagnostic yield vary substantially across disease entities. Methods:We retrospectively evaluated 165 patients referred for genetic testing due to suspected inherited kidney disease. Patients were classified into three clinical groups: polycystic kidney disease, Alport syndrome, and other syndromic patients with inherited kidney diseases. Genetic analysis was performed using NGS with Human Phenotype Ontology–based gene filtering and included evaluation of both single-nucleotide variants and copy number variations. Results: Overall diagnostic yield differed markedly between groups. A molecular diagnosis was achieved in 71.4% of Alport patients, 41.0% of PKD patients, and 70.2% of patients in the Other syndromic group. In the Alport group, variants were identified exclusively in COL4A3, COL4A4, and COL4A5, with pathogenicity and gene involvement correlating with disease severity and the presence of extrarenal manifestations. The PKD group showed predominant involvement of PKD1, followed by PKHD1 and PKD2, while a substantial proportion of patients remained genetically negative, reflecting technical and biological complexity. The Other group exhibited pronounced genetic heterogeneity, with variants distributed across multiple genes involved in tubular, glomerular, metabolic, and ciliopathy-related pathways. Computational assessments demonstrated that several variants of uncertain significance (VUS) were located in functionally critical domains and were predicted to disrupt protein stability, intermolecular interactions, or conserved structural motifs, thereby supporting the biological plausibility of their potential pathogenic impact. Conclusions: Phenotype-driven NGS enables effective molecular diagnosis across diverse inherited kidney diseases while revealing disease-specific differences in diagnostic yield and genotype–phenotype correlations. Systematic inclusion of variants of uncertain significance and careful integration of genetic and clinical data are essential for accurate interpretation and long-term patient management. Collectively, this study enhances understanding of inherited kidney diseases and underscores the value of integrating comprehensive genomic and computational approaches into routine nephrogenetic practice.

Background Nemaline Myopathy (NM) is a rare genetic disorder that affects muscle function and is characterized by the presence of nemaline rods in muscle fibers. These rods are abnormal structures that interfere with muscle contraction and can cause muscle weakness, respiratory distress, and other complications. NM is caused by variants in several genes, including TNNT1 , which encodes the protein troponin T1. NM is inherited in an autosomal recessive pattern. The prevalence of heterozygous TNNT1 variants has been reported to be 1/152,000, indicating that the disease is relatively rare. Objective Investigation of TNNT1 gene variants that may cause cretin kinase elevation. Methods Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and family segregation was done by Sanger sequencing. Results In this study, we report a 5-year-old girl with a novel variant recessive congenital TNNT1 myopathy. The patient had a novel homozygous (c.271_273del) deletion in the TNNT1 gene that is associated with creatine kinase elevation, which is a marker of muscle damage. Conclusion This case expands the phenotypic spectrum of TNNT1 myopathy and highlights the importance of genetic testing and counseling for families affected by this rare disorder. In this study provides valuable insights into the genetic basis of NM and highlights the importance of early diagnosis and management for patients with this rare disorder. Further research is needed to better understand the pathophysiology of TNNT1 myopathy and to develop effective treatments for this debilitating condition.

Purpose: Although chemotherapy is one of the standard treatments for gastric cancer, the disease’s resistance mechanisms continue to limit the survival rates. B7H6 (NCR3LG1), an immune checkpoint belonging to the B7 family, is significantly overexpressed in gastric cancer. This work investigated the possibility of using B7H6 suppression to improve the effectiveness of the widely used chemotherapy medication docetaxel. Materials and Methods: In this study, MKN-45 gastric cancer cells were transfected for 24 h with siRNA targeting B7H6, and then, docetaxel was added at optimal inhibitory doses (IC25 and IC50). To assess the impact of this combination therapy, cellular viability, proliferation, and migration were assessed using MTT assay, colony-forming unit assay, and wound-healing assay, respectively. Additionally, apoptosis and cell cycle status were evaluated by flow cytometry. Moreover, using qRT-PCR, the gene expression of B7H6 and indicators associated with apoptosis was also examined. Results: The sensitivity of MKN-45 cells to docetaxel was greatly increased by the siRNA-mediated knockdown of B7H6, resulting in a decrease in the drug’s IC50 value. When compared to each therapy alone, the combination of B7H6 siRNA plus docetaxel at IC50 levels exhibited a significant increase in apoptosis rate. The volume of cells arrested at the sub-G1 and G2-M phase was shown to rise when B7H6 siRNA transfection was combined with docetaxel. Furthermore, the combination treatment significantly decreased the ability of cells to migrate and form colonies. Conclusions: B7H6 suppression increases the susceptibility of MKN-45 gastric cancer cells to docetaxel treatment, resulting in decreased cellular proliferation and increased rates of apoptosis. The present work underscores the possibility of enhancing treatment results in gastric cancer by merging conventional chemotherapy with gene-silencing approaches.