Unveiling New Clinical and Genetic Insights in Ultra-Rare Intellectual Disability Phenotypes: A Study of a Turkish Cohort.

Intellectual disability (ID) is defined as a severe impairment in reasoning, learning, and problem-solving abilities along with adaptive behavior that occurs before the age of 18 years. The present study aimed to present the clinical and genetic data of a cohort of Turkish pediatric patients diagnosed with the ultrarare (which only up to 20 cases having been reported in the relevant literature thus far) ID phenotype. A total of 29 patients from 26 different families, who were diagnosed with ultrarare ID upon whole exome sequencing (WES) analysis, were included in the study.

A Novel Variant in an Asymptomatic Adolescent Girl with Progressive Cavitating Leukoencephalopathy.

Introduction: Pathogenic variants in several genes encoding components of the mitochondrial respiratory chain have been linked to various clinical phenotypes such as progressive cavitating leukoencephalopathy (PCL). The association between PCL, previously linked to numerous gene mutations in the literature, and the gene mutations has emerged as a recent and noteworthy discovery. PCL is generally diagnosed in symptomatic patients during the early years of life, mostly in infancy.

Nebivolol, an FDA-Approved Drug, Has General Antibacterial and Antibiofilm Effects and Increases Tolerance to Ciprofloxacin.

Background: The repurposing of approved drugs for new activities is gaining widespread attention, including drugs that have antibacterial properties. Nevertheless, besides the benefits of repurposing drugs, the discovery of new antibiotic activity in commonly used medicines raises concerns about inducing antibiotic tolerance and resistance due to the stress produced by the drugs. We found that nebivolol, which is used to treat hypertension, also has antibacterial activity.

A comprehensive assessment of the cholinergic-supporting and cognitive-enhancing effects of Rosa damascena Mill. (Damask rose) essential oil on scopolamine-induced amnestic rats.

Introduction: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues.

Methods: The control, amnesia (scopolamine, 1 mg/kg/i.

Discovery of a novel homozygous SOD1 truncating variant bolsters infantile SOD1 deficiency syndrome.

Objective: Superoxide dismutase 1 (SOD1) is an important antioxidant enzyme whose main function is to neutralise superoxide free radicals in the cytoplasm. Heterozygous variants in SOD1 are responsible for a substantial percentage of familial amyotrophic lateral sclerosis (ALS) cases. Recently, several reports have shown that biallelic loss of SOD1 function results in a novel phenotype called infantile SOD1 deficiency syndrome, which is consistent with a recessive pattern of inheritance and can be distinguished from typical (adult-onset) ALS.

Expanding the clinical and genetic landscape of (developmental) epileptic encephalopathy with spike-and-wave activation in sleep: results from studies of a Turkish cohort.

The terms developmental epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS) designate a spectrum of conditions that are typified by different combinations of motor, cognitive, language, and behavioral regression linked to robust spike-and-wave activity during sleep. In this study, we aimed at describing the clinical and molecular findings in "(developmental) epileptic encephalopathy with spike-and-wave activation in sleep" (D)EE-SWAS) patients as well as at contributing to the genetic etiologic spectrum of (D)EE-SWAS. Single nucleotide polymorphism (SNP) array and whole-exome sequencing (WES) techniques were used to determine the underlying genetic etiologies.

A Rare Presentation of Homozygous Pathogenic Variant in Gene with Salt-Wasting Crisis in a Neonate.

Introduction: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from isolated glucocorticoid deficiency or unresponsiveness to adrenocorticotropic hormone. Patients with FGD usually present in infancy or early childhood with hyperpigmentation, recurrent infections, and hypoglycemia. The salt-wasting crisis is rare.

The first Turkish family with a novel biallelic missense variant of the ALKBH8 gene: A study on the clinical and variant spectrum of ALKBH8-related intellectual developmental disorders.

ABH8, the protein encoded by the ALKBH8 gene, modifies tRNAs by methylating their anticodon wobble uridine residues. The variations in the ALKBH8 gene are associated with the "intellectual developmental disorder, autosomal recessive type 71" (MIM: 618504) phenotype in the OMIM database. This phenotype is characterized by global developmental delay, facial dysmorphic features, and psychiatric problems.

Prediction of molecular phenotypes for novel SCN1A variants from a Turkish genetic epilepsy syndromes cohort and report of two new patients with recessive Dravet syndrome.

Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) are both epilepsy syndromes that can be attributed to deleterious mutations occurring in SCN1A, the gene encoding the pore-forming α-subunit of the Na 1.1 voltage-gated sodium channel predominantly expressed in the central nervous system. In this research endeavor, our goal is to expand our prior cohort of Turkish patients affected by SCN1A-positive genetic epilepsy disorders.

Mechanistic insights into the inhibition of human placental glutathione S-transferase P1-1 by abscisic and gibberellic acids: An integrated experimental and computational study.

The interactions of the classic phytohormones gibberellic acid (gibberellin A , GA ) and abscisic acid (dormin, ABA), which antagonistically regulate several developmental processes and stress responses in higher plants, with human placental glutathione S-transferase P1-1 (hpGSTP1-1), an enzyme that plays a role in endo- or xenobiotic detoxification and regulation of cell survival and apoptosis, were investigated. The inhibitory potencies of ABA and GA against hpGSTP1, as well as the types of inhibition and the kinetic parameters, were determined by making use of both enzyme kinetic graphs and SPSS nonlinear regression models. The structural basis for the interaction between hpGSTP1-1 and phytohormones was predicted with the aid of molecular docking simulations.

Meropenem in combination with baicalein exhibits synergism against extensively drug resistant and pan-drug-resistant Acinetobacter baumannii clinical isolates in vitro.

Several studies have demonstrated that the effectiveness of carbapenems against drug-resistant Acinetobacter baumannii infections has been decreasing. Combination therapy with two or more drugs is currently under investigation to overcome the emerging resistance against carbapenems. In this study, we tested the possible synergistic interactions of a potent antibacterial flavonoid, baicalein, with meropenem to illustrate this duo's antibacterial and antibiofilm effects on 15 extensively drug resistant or pan-drug-resistant (XDR/PDR) A.

Conversations in the Gut: The Role of Quorum Sensing in Normobiosis.

An imbalance in gut microbiota, termed dysbiosis, has been shown to affect host health. Several factors, including dietary changes, have been reported to cause dysbiosis with its associated pathologies that include inflammatory bowel disease, cancer, obesity, depression, and autism. We recently demonstrated the inhibitory effects of artificial sweeteners on bacterial quorum sensing (QS) and proposed that QS inhibition may be one mechanism behind such dysbiosis.

Investigation of the Possible Protective Effect of -Acetylcysteine (NAC) against Irinotecan (CPT-11)-Induced Toxicity in Rats.

Irinotecan (CPT-11) is a chemotherapeutic agent involved in the treatment regimens for several malignancies such as colorectal cancer. -acetylcysteine (NAC) is a strong antioxidant and anti-inflammatory agent used in the treatment of several diseases related to oxidative stress and inflammation. This study aimed at investigating whether NAC provides protection against hepatorenal and gastrointestinal tissue damage induced by CPT-11.

Protective effects of Rubus tereticaulis leaves ethanol extract on rats with ulcerative colitis and bio-guided isolation of its active compounds: A combined in silico, in vitro and in vivo study.

The aim of this study was to evaluate the therapeutic effect of active ethanol extract obtained from the leaves of Rubus tereticaulis (RTME) against colitis, and to purify major compounds from this extract by bioassay-directed isolation. Rats with colitis induced via intra-rectal acetic acid administration (5%, v/v) received RTME or sulfasalazine for three consecutive days. On day four, all rats were decapitated, and the colonic tissue samples were collected for macroscopic score, colon weight, reduced glutathione (GSH), myeloperoxidase (MPO), and malondialdehyde (MDA) analyses.

Protective Effects of Alpha-Lipoic Acid against 5-Fluorouracil-Induced Gastrointestinal Mucositis in Rats.

Alpha-lipoic acid (ALA) is extensively utilized in multivitamin formulas and anti-aging products. The purpose of this study was to investigate the potential protective benefits of ALA on 5-fluorouracil (5-FU)-induced gastrointestinal mucositis in Wistar albino rats. Tissues from the stomach, small intestine, and large intestine were excised, and blood sera were obtained to identify biochemical indices such as TNF-α, IL-1β, MDA, GPx, SOD, MMP-1, -2, -8, and TIMP-1.

Study of ten causal genes in Turkish patients with clinically suspected maturity-onset diabetes of the young (MODY) using a targeted next-generation sequencing panel.

Background: Maturity-onset diabetes of the young (MODY), which is the most common cause of monogenic diabetes, has an autosomal dominant pattern of inheritance and exhibits marked clinical and genetic heterogeneity. The aim of the current study was to investigate molecular defects in patients with clinically suspected MODY using a next-generation sequencing (NGS)-based targeted gene panel.

Methods: Candidate patients with clinical suspicion of MODY and their parents were included in the study.

Anti-Virulence Activity of 3,3'-Diindolylmethane (DIM): A Bioactive Cruciferous Phytochemical with Accelerated Wound Healing Benefits.

Antimicrobial resistance is among the top global health problems with antibacterial resistance currently representing the major threat both in terms of occurrence and complexity. One reason current treatments of bacterial diseases are ineffective is the occurrence of protective and resistant biofilm structures. Phytochemicals are currently being reviewed for newer anti-virulence agents.

In Vitro and In Silico Evaluation of ACE2 and LOX Inhibitory Activity of Origanum Essential Oils and Carvacrol.

spp. are used both for culinary purposes and for their biological activities. In this study, commercial , and essential oils and their prominent constituent carvacrol were evaluated for their and angiotensin-converting enzyme 2 and lipoxygenase enzyme inhibitory potentials.

A multi-parameter evaluation of the neuroprotective and cognitive-enhancing effects of Origanum onites L. (Turkish Oregano) essential oil on scopolamine-induced amnestic rats.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions (dementia) and represents a growing public health concern since the population in the age groups at risk is increasing. The latter raises an urgent need to translate research findings in the basic brain and behavioral sciences into anti-AD drugs and disease-modifying therapies. Origanum onites (L.

Isolation, Characterization and In Silico Studies of Secondary Metabolites from the Whole Plant of Peşmen & Erik.

species are frequently used worldwide in the treatment of various diseases, such as inflammatory and autoimmune disorders as well as metabolic and neurodegenerative diseases, due to the large number of secondary metabolites they contain. The present study was performed on , which is a narrow endemic species for the flora of Turkey, and resulted in the isolation of nine known compounds, 6,3'-disinapoyl-sucrose (), 6--sinapoyl,3'--trimethoxy-cinnamoyl-sucrose (tenuifoliside C) (), 3'--(-methyl-feruloyl)-sucrose (), 3'--(sinapoyl)-sucrose (), 3'--trimethoxy-cinnamoyl-sucrose (glomeratose) (), 3'--feruloyl-sucrose (sibiricose A5) (), sinapyl alcohol 4--glucoside (syringin or eleutheroside B) (), liriodendrin (), and 7,4'-di--methylquercetin-3--β-rutinoside (ombuin 3--rutinoside or ombuoside) (). The structures of the compounds were determined by the spectroscopic methods including 1D-NMR (H NMR, C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC), and HRMS.

Inhibitory Effects of Artificial Sweeteners on Bacterial Quorum Sensing.

Despite having been tagged as safe and beneficial, recent evidence remains inconclusive regarding the status of artificial sweeteners and their putative effects on gut microbiota. Gut microorganisms are essential for the normal metabolic functions of their host. These microorganisms communicate within their community and regulate group behaviors via a molecular system termed quorum sensing (QS).

3-Hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one and 3-hydroxy-6H-benzo[c]chromen-6-one act as on-off selective fluorescent sensors for Iron (III) under in vitro and ex vivo conditions.

Regarding the abundant use of metals for different purposes, it becomes more critical from various scientific and technological perspectives to discover novel agents as selective probes for the detection of specific metals. In our previous studies, we have shown that aqueous solutions of natural urolithins (i.e.

Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Quorum Sensing.

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe.