A Comprehensive Overview of NF1 Mutations in Iranian Patients.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene. This disorder shows nearly complete penetrance and high phenotypic variability. We used the whole-exome sequencing technique to identify mutations in 32 NF1 cases from 22 Iranian families. A total of 31 variants, including 30 point mutations and one large deletion, were detected. In eight cases, variants were inherited, while they were sporadic in the remaining. Seven novel variants, including c.5576 T > G, c.6658_6659insC, c.2322dupT, c.92_93insAA, c.4360C > T, c.3814C > T, and c.4565_4566delinsC, were identified. The current study is the largest in terms of the sample size of Iranian NF1 cases with identified mutations. The results can broaden the spectrum of NF1 mutations and facilitate the process of genetic counseling in the affected families.

Therapeutic effects of nanosilibinin in valproic acid-zebrafish model of autism spectrum disorder: Focusing on Wnt signaling pathway and autism spectrum disorder-related cytokines.

In this study, we delved into the intricate world of autism spectrum disorder (ASD) and its connection to the disturbance in the Wnt signaling pathway and immunological abnormalities. Our aim was to evaluate the impact of silibinin, a remarkable modulator of both the Wnt signaling pathway and the immune system, on the neurobehavioral and molecular patterns observed in a zebrafish model of ASD induced by valproic acid (VPA). Because silibinin is a hydrophobic molecule and highly insoluble in water, it was used in the form of silibinin nanoparticles (nanosilibinin, NS). After assessing survival, hatching rate, and morphology of zebrafish larvae exposed to different concentrations of NS, the appropriate concentrations were chosen. Then, zebrafish embryos were exposed to VPA (1 µM) and NS (100 and 200 µM) at the same time for 120 h. Next, anxiety and inattentive behaviors and the expression of CHD8, CTNNB, GSK3beta, LRP6, TNFalpha, IL1beta, and BDNF genes were assessed 7 days post fertilization. The results indicated that higher concentrations of NS had adverse effects on survival, hatching, and morphological development. The concentrations of 100 and 200 µM of NS could ameliorate the anxiety-like behavior and learning deficit and decrease ASD-related cytokines (IL1beta and TNFalpha) in VPA-treated larvae. In addition, only 100 µM of NS prevented raising the gene expression of Wnt signaling-related factors (CHD8, CTNNB, GSK3beta, and LRP6). In conclusion, NS treatment for the first 120 h showed therapeutic effect on an autism-like phenotype probably via reducing the expression of pro-inflammatory cytokines genes and changing the expression of Wnt signaling components genes.

"Effect of Sunset Yellow on Testis: Molecular Evaluation, and Protective Role of Coenzyme Q10 in Male Sprague-Dawley Rats".

In recent years, Sunset Yellow (SY) has been widely used as a food additive, sparking debates about its potential toxicity. This research aims to investigate SY's effects at both the molecular and histopathological levels, along with the protective benefits of Coenzyme Q10 (CoQ10) supplementation in male rat testes. Forty-two male Sprague-Dawley rats were randomly divided into six groups (n = 7) and given daily oral gavages for six weeks. The groups included: a low dose of Sunset Yellow (2.5 mg/kg/day), a high dose of Sunset Yellow (70 mg/kg/day), CoQ10 (10 mg/kg/day), CoQ10 with the low dose of Sunset Yellow, CoQ10 with the high dose of Sunset Yellow, and deionized water as a control. After anesthesia, the rats' testes were removed for molecular and histological analysis. The findings showed a dose-dependent rise in the expression of oxidative stress genes (Sod, Gpx, and Cata) and a notable decrease in the expression of the steroidogenic acute regulatory (Star) gene (P value < 0.05) with increasing SY doses. Histological results supported these outcomes. Additionally, there was no significant distinction between rats treated with CoQ10 along with low doses of Sunset Yellow (CoQ10+LD) and control rats given low doses of Sunset Yellow (SY-LD). Conclusions: This study illustrates that SY, as an artificial food dye, has harmful effects on the male reproductive system, while the utilization of CoQ10 can alleviate the negative impacts of SY exposure.

Jaberi-Elahi syndrome: Exploring a novel GTPBP2 mutation and a literature review.

Jaberi-Elahi syndrome is an extremely rare genetic disease caused by pathogenic variants in GTPBP2. The core symptoms of this disease are intellectual disability, motor development delay, abnormal reflexes, skeletal abnormalities, and visual impairment. In this study, we describe a three-year-old girl with a novel homozygous variant in GTPBP2 and a phenotype overlapping with Jaberi-Elahi syndrome. This variant (NM_019096.5:c.1289T > C, p.Leu430Pro) was identified by Whole Exome Sequencing and confirmed by Sanger sequencing although remains classified as VUS based on ACMG criteria. The proband demonstrated motor and intellectual developmental delay, muscle weakness, language disorder, facial dysmorphism, and poor growth. Hitherto, twenty-seven individuals with Jaberi-Elahi syndrome have been reported in the literature. This study, describes a review of the symptoms related to the Jaberi-Elahi syndrome. A large numbers of patients manifest motor development delay (26/28), sparse hair (26/28), and speech disorder (24/28). Moreover, a significant fraction of patients suffer from intellectual disability (23/28), hypotonia (23/28), skeletal problems (23/28), and visual impairment (18/28). In spite of previous patients, the proband in this study did not exhibit any skeletal abnormalities. In summary, we present evidence implicating a novel missense variant in Jaberi-Elahi syndrome, expanding and refining the genetic spectrum of this condition.

Two siblings with PEX11B-related peroxisome biogenesis disorder.

The PEX11ß gene contains four exons and encodes peroxisomal membrane protein 11ß, which is involved in peroxisome proliferation and division. Pathogenic variants in this gene result in a rare genetic disorder with autosomal recessive inheritance called peroxisome biogenesis disorder 14B (MIM: 614920). Here, we report two affected siblings with a novel variant (NM_003846: c.11G > A, p. Trp4Ter) in the PEX11ß gene that was identified by whole exome sequencing and confirmed by Sanger sequencing. The proband is a 22-year-old Iranian female who was born to consanguineous parents. The homozygous variant (NM_003846: c.11G > A, p. Trp4Ter) in the PEX11ß gene was identified in the proband, who presented with cataracts, strabismus, nystagmus, intellectual disability, developmental delay, speech disorders, dry skin, and behavioral problems. Her younger affected brother, who had the same homozygous variant, suffered from similar but slightly milder symptoms. This paper reports the seventh family in the world with novel pathogenic variants in the PEX11ß gene as the cause of peroxisome biogenesis disorder 14B. Additionally, the phenotypes of the previously reported patients are reviewed. Some of the phenotypes, such as bilateral congenital cataracts and intellectual disability, were present in all patients. However, other observed symptoms in previous cases, such as abnormal gait, myopia, abnormal muscle strength, hearing loss, gastrointestinal problems, skeletal disorders, and seizures, were not observed in the patients of this study. Further studies on this disorder could be valuable in determining the precise phenotype characteristics of this disease.

The Effect of Mesenchymal Stem Cells Derived-Conditioned Media in Combination with Oral Anti-Androgenic Drugs on Male Pattern Baldness: An Animal Study.

OBJECTIVE: Androgenetic alopecia (AGA) is a prevalent form of hair loss, mainly caused by follicular sensitivity to androgens. Despite developing different anti-androgen treatment options, the success rate of these treatments has been limited. Using animal models, this study evaluated the therapeutic effects of umbilical cord (UC) stem cell conditioned media (CM) combined with oral anti-androgens for hair regeneration. MATERIALS AND METHODS: In this experimental study, Poloxamer 407 (P407) was used as a drug carrier for subcutaneous testosterone injection. AGA models were treated with oral finasteride, oral flutamide, and CM injections. Samples were thoroughly evaluated and compared using histological, stereological, and molecular analyses. RESULTS: Injecting CM-loaded hydrogel alone or combined with oral intake of anti-androgens improved hair regeneration. These treatments could promote hair growth by inducing hair follicles in the anagen stage and shortening the telogen and catagen phases. Furthermore, the combination treatment led to an upregulation of hair induction gene expression with a downregulation of inflammation genes. CONCLUSION: Through a reduction in inflammation, injection of CM-loaded hydrogel alone or combined with oral intake of anti-androgens induces the hair cell cycle with regeneration in damaged follicles. Hence, this could be a promising therapeutic method for AGA patients.

Protective Effect of Docetaxel Against Autophagy-Related Genes in Vitrification of Mouse Metaphase II Oocytes.

Background: Autophagy is a conservative mechanism for cell survival as the main response of cells to stress conditions. The present study aimed to assess the effect of docetaxel on the survival, fertilization, and expression of autophagy-related genes in vitrified oocytes. Methods: The study was conducted in 2018 at the Stem Cells Technology Research Center, Shiraz University of Medical Sciences (Shiraz, Iran). Denuded oocytes were randomly selected and assigned to five groups, namely control (n=133), docetaxel (n=136), docetaxel+cryoprotectants (n=146), docetaxel+vitrification (n=138), and vitrification (n=145). The effect of vitrification on the expression of autophagy-related gene 5 (ATG5) and Beclin-1 was determined using a real-time polymerase chain reaction. Data were analyzed using SPSS software (version 26.0) and GraphPad Prism 9. Results: Survival and fertilization rates in each experimental group were significantly reduced compared to the control group (P=0.001). After in vitro fertilization of oocytes, the 2-cell formation rate was significantly reduced in the docetaxel+vitrification and vitrification groups compared to the control and docetaxel groups (P=0.001 and P=0.001, respectively). Pre-incubation of oocytes with docetaxel reduced gene expression levels of Beclin-1 and ATG5 in the docetaxel+cryoprotectants and docetaxel+vitrification groups (P=0.001 and P=0.019, respectively). The expression level of these genes was also reduced in the docetaxel group compared to the control group (P=0.001). Conclusion: Incubation of mouse metaphase II oocytes with docetaxel prior to vitrification reduced the expression of autophagy-related genes and increased survival and fertilization rates compared to untreated oocytes.

Novel insight into the phenotype of microcephaly 19 in the patient with missense COPB2 mutation.

COPB2 gene encodes the Coatomer Protein Complex Subunit Beta-2 that plays a crucial role in the cellular vesicle transport system and it is essential for brain development during embryogenesis. Mutations in COPB2 lead to an extremely rare genetic disease named Microcephaly type 19 with autosomal recessive inheritance. This study describes a missense pathogenic homozygous variant (NM_004766.3:c.760 C > T, p.Arg254Cys) in the COPB2 gene, which was identified by Whole-Exome sequencing and confirmed by Sanger sequencing. The proband of the present study is an eight-and-a-half-year-old Iranian female who was born to consanguineous parents. She manifests global developmental delay, intellectual disability, microcephaly, seizures, spasticity, strabismus, and failure to thrive symptoms. Moreover, she is unable to stand, walk, or speak. Here we report the second homozygous mutation (NM_004766.3:c.760 C > T, p.Arg254Cys) in the COPB2 gene in the second family in the world with MCPH19. The responsible variant (NM_004766.3:c.760 C > T, p.Arg254Cys) for the observed symptoms in the proband was identical to the identified variant in the previously reported Caucasian/Native American family. Sharing this extremely rare pathogenic variant in two families with different origins is an extraordinary event that could aid us to determine the phenotype of this disease more precisely. Eventually, we provide a case-based review of the clinical features and compared our findings to the previously reported family for a better understanding of the clinical presentation of Microcephaly type 19 disease.

Simple methods for cerebrospinal fluid collection in fetal, neonatal, and adult rat.

BACKGROUND: Cerebrospinal fluid (CSF) collection and its analysis are common medical practices useful in the diagnosis, therapy, and prevention of central nervous system (CNS) disorders. In recent years, several types of research have improved our insight into CSF and its role in health and disease. Yet, many characteristics of this fluid remain to be fully understood. NEW METHODS: Here, we describe how to collect CSF from embryonic, postnatal, and adult stages of the rat. In adults, CSF can be collected through simple stereotaxic surgery to expose the membrane overlying the cisterna magna (CM) of an anesthetized rat and collection of CSF through micropipette puncture through the membrane. In embryos and pups, CSF is aspirated, using a fire-polished micro-capillary pipette, from the CM of animals. RESULTS: Application of these methods provides the maximum volume of pure, uncontaminated CSF (embryonic day 19: 10-15 microliter, postnatal day 5: 20-30 microliter, adults: 100-200 microliter) with a success rate of approximately 95% in every age. COMPARISON WITH EXISTING METHODS: Compared to the existing protocols, these methods obtain considerable volumes of CSF, which may accelerate the measurement of biological markers in this fluid. Also, these techniques do not require surgical skills and according to the practical points mentioned during sampling, the procedures can be performed in rapid fashion. CONCLUSION: We describe simple methods for collecting CSF in live rats. These protocols provide clean, uncontaminated CSF for experiments to understand the exact role of this fluid in the development and maintenance of the CNS health.

Oxytocin Receptor Expression in Hair Follicle Stem Cells: A Promising Model for Biological and Therapeutic Discovery in Neuropsychiatric Disorders.

The intricate nature of the human brain and the limitations of existing model systems to study molecular and cellular causes of neuropsychiatric disorders represent a major challenge for basic research. The promising progress in patient-derived stem cell technology and in our knowledge on the role of the brain oxytocin (OXT) system in health and disease offer new possibilities in that direction. In this study, the rat hair follicle stem cells (HFSCs) were isolated and expanded in vitro. The expression of oxytocin receptors (OXTR) was evaluated in these cells. The cellular viability was assessed 12 h post stimulation with OXT. The activation of OXTR-coupled intracellular signaling cascades, following OXT treatment was determined. Also, the influence of OXT on neurite outgrowth and cytoskeletal rearrangement were defined. The assessment of OXTR protein expression revealed this receptor is expressed abundantly in HFSCs. As evidenced by the cell viability assay, no adverse or cytotoxic effects were detected following 12 h treatment with different concentrations of OXT. Moreover, OXTR stimulation by OXT resulted in ERK1/2, CREB, and eEF2 activation, neurite length alterations, and cytoskeletal rearrangements that reveal the functionality of this receptor in HFSCs. Here, we introduced the rat HFSCs as an easy-to-obtain stem cell model that express functional OXTR. This cell-based model can contribute to our understanding of the progression and treatment of neuropsychiatric disorders with oxytocinergic system deficiency.

A Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant.

BACKGROUND: The LIPA gene on chromosome 10q23.31 contains 10 exons and encodes lipase A, the lysosomal acid lipase (LAL) containing 399 amino acids. Pathogenic variants in the LIPA result in autosomal recessive Wolman disease and cholesteryl ester storage disease (CESD). Here, we report a novel missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of LIPA in an Iranian family with fatty liver disease identified by whole-exome sequencing and confirmed by Sanger sequencing. METHODS: A 28-year-old woman referred with lean NASH cirrhosis and extremely high cholesterol levels. Fatty liver disease was found in six of her family members using vibration-controlled transient elastography (VCTE). Baseline routine laboratory tests were performed and whole-exome sequencing and confirmation by Sanger sequencing were done. RESULTS: The index case had severe dyslipidemia and cirrhosis despite a body mass index of 21.09 kg/m2 . Six other family members had dyslipidemia and fatty liver or cirrhosis. A homozygous missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of LIPA which caused LAL-D was found to be associated with fatty liver disease and/or cirrhosis. CONCLUSION: A homozygous missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of the LIPA gene which caused LAL-D was found to be associated with dyslipidemia, fatty liver disease and/or cirrhosis in six members of an Iranian family. These results should be confirmed by functional studies and extending the study to at least three families.

Novel insight into the ectodermal dysplasia 11A: Splicing variant of the EDARADD gene in a family with clinical variability and literature review.

Pathogenic variants in the EDARADD gene result in autosomal recessive and autosomal dominant ectodermal dysplasia. This article reports on the fourth family in the world with ectodermal dysplasia 11A (ECTD11A) cause from a novel splicing variant in the EDARADD gene, identified by whole exome sequencing and confirmed by Sanger sequencing. The proband and his mother were heterozygous for the detected variant (NM_145861.4:c.161-2A>T). The proband manifests unusual symptoms including hyperkeratotic plaques, slow-growing hair, recurrent infection, and pectus excavatum. His mother presents hypohidrosis, extensive tooth decay, fragile nails, and sparse hair. Further studies on ECTD11A patients could be useful to characterizing the phenotype features more precisely.

Short-term beneficial effects of human dental pulp stem cells and their secretome in a rat model of mild ischemic stroke.

Although cell therapy has been applied in regenerative medicine for decades, recent years have seen greatly increased attention being given to the use of stem cell-based derivatives such as cell-free secretome. Dental pulp stem cells (DPSCs) are widely available, easily accessible, and have high neuroprotective and angiogenic properties. In addition, DPSC-derived secretome contains a rich mixture of trophic factors. The current investigation evaluated the short-term therapeutic effects of human DPSCs and their secretome in a rat model of mild ischemic stroke. Mild ischemic stroke was induced by 30 min middle cerebral artery occlusion, and hDPSCs or their secretome was administered intra-arterially and intranasally. Neurological function, infarct size, spatial working memory, and relative expression of seven target genes in two categories of neurotrophic and angiogenic factors were assessed three days after stroke. In the short-term, all treatments reduced the severity of neurological and histological deficits caused by ischemic stroke. Moreover, transient middle cerebral artery occlusion led to the striatal and cortical over-expression of BDNF, NT-3, and angiogenin, while NGF and VEGF expression was reduced. Almost all interventions were able to modulate the expression of target genes after stroke. The obtained data revealed that single intra-arterial administration of hDPSCs or their secretome, single intranasal transplantation of hDPSCs, or repeated intranasal administration of hDPSC-derived secretome was able to ameliorate the devastating effects of a mild stroke, at least in the short-term.

A novel nonsense variant in the ATL3 gene is associated with disturbed pain sensitivity, numbness of distal limbs and muscle weakness.

Introduction Hereditary sensory neuropathy (HSN) describes as a heterogeneous group of peripheral neuropathies. HSN type 1 (HSN1) is one subtype characterized by distal sensory impairment that occurs in the form of numbness, tingling, or pain. To date, only two variants in the atlastin GTPase 3 (ATL3) gene have been identified that result in hereditary sensory neuropathy type 1F (HSN1F) with autosomal dominantinheritance. Methods We sudied and examined who present with sensory disturbances and muscle weakness in their lower limb. Patients underwent Whole Exome Sequencing and Sanger sequencing was performed in families for validation of detected variant. Results Here, we identified two Iranian families carrying the novel heterozygous stop variant NM_015459.5: c.16C>T, p.Arg6Ter in ATL3 that led to disturbed pain and touch sensitivity. This variant in the ATL3 gene was detected in both families (NM_015459.5: c.16C>T, p.Arg6Ter) by whole-exome sequencing and confirmed by Sanger sequencing. Conclusion In this study, the subjects manifested weakness of distal limb muscles and numbness of the lower extremities. In addition, some unusual features, including hearing problems and inability to sit and walk presented in one of the patients. Eventually, we provide a case-based review of the clinical features associated with HSN1F. Hitherto, only 11 patients with HSN1F have been reported. We compared our findings to previously reported cases, suggesting that the clinical features are generally variable in the HSN1F patients.

NRXN3 mutations cause developmental delay, movement disorder, and behavioral problems: CRISPR edited cells based WES results.

NRXN3geneencodesneurexin-III which is a Neural Cell Adhesion Molecule (NCAM) with important synaptic functions in the brain. Neurexin-III deficiency could affect synapse development, synaptic signaling and neurotransmitter release. Hitherto, there is no related disorder in the OMIM due to NRXN3 mutation. In this study, two unrelated Iranian families with homozygous (NM_001330195.2:c.3995G>A, p.Arg1332His) and compound heterozygous (NM_001330195.2:c.4442G>A, p.Arg1481Gln; c.3142+3A>G) variants in theNRXN3gene were detected for the first time. The proband of the first family manifested learning disability, developmental delay, inability to walk, and behavioral problems such as difficulty in social communication. Also, global development delay, intellectual disability, abnormal gait, severe speech problems, muscle weakness, and behavioral problems were observed in the affected individual in the second family. In addition, deciphering the pathogenicity of NRXN3 variants was done by functional studies such as CRISPR edited cells, in-silico analysis, and NGS results. All of these data together with phenotype similarity between observed phenotypes in our patients and manifested symptoms in the homozygousNrxn3α/ß knockout mice, demonstrate the homozygous and compound heterozygous mutations of NRXN3 could cause a novel syndromic mendelian genetic disorder with autosomal recessive inheritance. The main phenotype of patients with neurexin-III deficiency includes developmental delay, learning disability, movement disorder, and behavioral problems.

Intronic OTOF mutation causes an atypical splicing defect resulting in auditory neuropathy spectrum disorder.

Pathogenic variants in OTOF cause auditory neuropathy spectrum disorder (ANSD), namely prelingual nonsyndromic ANSD and temperature-sensitive ANSD (TS-ANSD). All study subjects provided blood sample for genetic analysis and sequencing. Wholeexome sequencing was carried out to identify the causative pathogenic variant. RNAwas extracted to analyse the messenger RNA (mRNA) resulting from the transcription of OTOF. Here, we identified a family with OTOF-related ANSD. This disorder was caused by an intronic mutation in OTOF (NM_194248: c.2406>4A[G). In further analysis, we proved that this variant causes a splicing defect resulting in the omission of exon 20 from the mRNA transcribed from OTOF. In this study, we demonstrated that the variant is four nucleotides away from the conventional splicing site, and our findings suggest that splicing mechanisms need to be better understood, as well as how neighbouring regions may impact splicing.

EPS8 variant causes deafness, autosomal recessive 102 (DFNB102) and literature review.

Pathogenic variants in the EPS8 gene result in nonsyndromic hearing loss. This gene encodes the EPS8 protein in cochlear inner hair cells and performs critical roles in stimulating actin polymerization and bundling. Thus far, only four pathogenic variations in EPS8 have been described. In this study, we report the fifth pathogenic variant in the EPS8 gene in an Iranian patient with DFNB102. Furthermore, we review literature cases with EPS8 mutations.

The third patient of ACACA-related acetyl-CoA carboxylase deficiency with seizure and literature review.

Pathogenic variants in ACACA are the cause of acetyl-CoA carboxylase deficiency with an autosomal recessive inheritance that is identified by hypotonia, motor, and intellectual developmental delay. In this article, we describe a seven-year-old boy who is the child of consanguineous parents with a homozygous variant in ACACA (NM_198834.3:c.6641C > A, p.P2214H) that was detected by Whole-Exome Sequencing and confirmed by Sanger sequencing. This is the first reported patient of acetyl-CoA carboxylase deficiency that results from a homozygous pathogenic variant in the ACACA gene in the Iranian family. The proband presents with motor and intellectual developmental delay, muscle weakness, language disorder, facial dysmorphism, and poor growth. The patient discussed here is similar to other patients that were previously published; however, we were able to identify seizure that has hitherto not been reported. This paper describes the third person with a novel variant in the ACACA gene in the world that accounts for acetyl-CoA carboxylase deficiency and implicates the clinical spectrum of the disease. Finally, we describe an individual-based review of the symptoms associated with acetyl-CoA carboxylase deficiency. So far, only two acetyl-CoA carboxylase deficiency patients have been reviewed in the literature.

The beneficial effects of chick embryo extract preconditioning on hair follicle stem cells: A promising strategy to generate Schwann cells.

The beneficial effects of hair follicle stem cells in different animal models of nervous system conditions have been extensively studied. While chick embryo extract (CEE) has been used as a growth medium supplement for these stem cells, this is the first study to show the effect of CEE on them. The rat hair follicle stem cells were isolated and supplemented with 10% fetal bovine serum plus 10% CEE. The migration rate, proliferative capacity and multipotency were evaluated along with morphometric alteration and differentiation direction. The proteome analysis of CEE content identified effective factors of CEE that probably regulate fate and function of stem cells. The CEE enhances the migration rate of stem cells from explanted bulges as well as their proliferation, likely due to activation of AP-1 and translationally controlled tumour protein (TCTP) by thioredoxin found in CEE. The increased length of outgrowth may be the result of cyclic AMP response element binding protein (CREB) phosphorylation triggered by active CamKII contained in CEE. Further, CEE supplementation upregulates the expression of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. The elevated expression of target genes and proteins may be due to CREB, AP-1 and c-Myc activation in these stem cells. Given the increased transcript levels of neurotrophins, VEGF, and the expression of PDGFR-α, S100B, MBP and SOX-10 protein, it is possible that CEE promotes the fate of these stem cells towards Schwann cells.

New thioxothiazolidinyl-acetamides derivatives as potent urease inhibitors: design, synthesis, in vitro inhibition, and molecular dynamic simulation.

To identify potent urease inhibitors, in the current study, a series of thioxothiazolidinyl-acetamides were designed and synthesized. The prepared compounds were characterized by spectroscopic techniques, including FTIR, 1HNMR, 13CNMR, and elemental analysis. In the enzymatic assessments, it was demonstrated that all derivatives had significant urease inhibition with IC50 values in the range of 1.473-9.274 µM in comparison with the positive control hydroxyurea (IC50 = 100.21 ± 2.5 µM) and thiourea (IC50 = 23.62 ± 0.84 µM). Compound 6i (N-benzyl-3-butyl-4-oxo-2-thioxothiazolidine-5-carboxamide) was the most active agent with an IC50 value of 1.473 µM. Additionally, kinetic investigation and in silico assessments of 6i was carried out to understand the type of inhibition and behavior of the most potent derivative within the binding site of the enzyme. Noteworthy, the anti-urease assay against P. vulgaris revealed 6e and 6i as the most active agents with IC50 values of 15.27 ± 2.40 and 17.78 ± 3.75 µg/mL, respectively. Antimicrobial evaluations of all compounds reveal that compounds 6n and 6o were the most potent antimicrobial agents against the standard and resistant S. aureus. 6n and 6o also showed 37 and 27% inhibition in the development of biofilm by S. aureus at 512 µg/ml. Furthermore, the MTT test showed no toxicity up to 100 µM. Taken together, the study suggests that the synthesized thioxothiazolidinyl-acetamides bases derivatives may serve as potential hits as urease inhibitors.