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In December 2019, a novel coronavirus crossed species barriers to infect humans and was effectively transmitted from person to person, leading to a worldwide pandemic. Development of effective clinical interventions, including vaccines and antiviral drugs that could prevent or limit theburden or transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health priority. It is thus of utmost importance to assess possible therapeutic strategies against SARS-CoV-2 using experimental models that recapitulate aspects of the human disease. Here, we review available models currently being developed and used to study SARS-CoV-2 infection and highlight their application to screen potential therapeutic approaches, including repurposed antiviral drugs and vaccines. Each identified model provides a valuable insight into SARS-CoV-2 cellular tropism, replication kinetics, and cell damage that could ultimately enhance understanding of SARS-CoV-2 pathogenesis and protective immunity.
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COVID-19 , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Modelos Teóricos , Pandemias , SARS-CoV-2RESUMO
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.
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Neuropatias Hereditárias Sensoriais e Autônomas , Doenças do Sistema Nervoso Periférico , Humanos , Hipestesia/genética , Irã (Geográfico) , Debilidade Muscular/genética , Dor/genética , Linhagem , GTP Fosfo-Hidrolases/genéticaRESUMO
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.
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AVC Isquêmico , Acidente Vascular Cerebral , Ratos , Humanos , Animais , Infarto da Artéria Cerebral Média/terapia , Polpa Dentária , Secretoma , Células-Tronco , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND: Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in YY1. In this study, we report a 10-year-old boy with a de novo novel pathogenic variant in YY1, the first Iranian patient with Gabriele-de Vries Syndrome. METHODS: The novel de novo pathogenic variant detected in this study (NM_003403:c.690delA, p.Glu231Ilefs*25) was identified by whole-exome sequencing and confirmed by Sanger sequencing. RESULTS: The proband presented with delayed motor and speech development, ataxia, abnormal gait, autistic behavior, brain atrophy, and severe learning disability. Finally, we provide a case-based review of the clinical features associated with Gabriele-de Vries Syndrome. Thus far, merely 13 Gabriele-de Vries Syndrome patients have been reported in the literature. CONCLUSION: The investigations for a suspected case of Gabriele-de Vries Syndrome must involve molecular diagnosis of the disease and its underlying genetic defect because the clinical investigations are generally variable and nonspecific.
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Deficiência Intelectual , Yin-Yang , Criança , Humanos , Deficiência Intelectual/genética , Irã (Geográfico) , Masculino , Fenótipo , Síndrome , Sequenciamento do ExomaRESUMO
BACKGROUND: Stem cell-based therapy has received considerable attention as a potential candidate in the treatment of ischemic stroke; however, employing an appropriate type of stem cells and an effective delivery route are still challenging. In the present study, we investigated the therapeutic effect of safe, noninvasive, and brain-targeted intranasal administration of hair follicle-derived stem cells (HFSCs) in a rat model of ischemic stroke. METHODS: Stem cells were obtained from the adult rat hair follicles. In experiment 1, stroke was induced by 30 min middle cerebral artery occlusion (MCAO) and stem cells were intranasally transplanted immediately after ischemia. In experiment 2, stroke was induced by 120 min MCAO and stem cells were administered 24 h after cerebral ischemia. In all experimental groups, neurological performance, short-term spatial working memory and infarct volume were assessed. Moreover, relative expression of major trophic factors in the striatum and cortex was evaluated by the quantitative PCR technique. The end point of experiment 1 was day 3 and the end point of experiment 2 was day 15. RESULTS: In both experiments, intranasal administration of HFSCs improved functional performance and decreased infarct volume compared to the MCAO rats. Furthermore, NeuN and VEGF expression were higher in the transplanted group and stem cell therapy partially prevented BDNF and neurotrophin-3 over-expression induced by cerebral ischemia. CONCLUSIONS: These findings highlight the curative potential of HFSCs following intranasal transplantation in a rat model of ischemic stroke.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Administração Intranasal , Animais , Isquemia Encefálica/terapia , Folículo Piloso , Infarto da Artéria Cerebral Média/terapia , Ratos , Células-Tronco , Acidente Vascular Cerebral/terapiaRESUMO
HYOU1 encodes a protein from the endoplasmic reticulum chaperone proteins, expressed to protect cellular mechanisms from stress such as hypoxia, insufficient energy and excessive or insufficient substances, and to restore cell homeostasis. In this study, we report a novel pathogenic variant in HYOU1. The proband, the second patient with pathogenic variant in HYOU1, was a female born to consanguineous parents. A novel homozygous pathogenic variant in HYOU1 (NM_001130991.3: c.1456C>T; p.Arg486Cys) was identified, causing anemia, thrombocytopenia and severe panleukopenia and immunodeficiency in the second month of age, leading to consistent high-grade fever, regression of brain functions and recurrent infections; ultimately resulting in the patient expiring at three and half months of age. Both parents are heterozygous for this variant and have no issues related to this study.
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Proteínas de Choque Térmico HSP70 , Síndromes de Imunodeficiência , Pancitopenia , Feminino , Proteínas de Choque Térmico HSP70/genética , Homozigoto , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/genética , Lactente , Mutação , Pancitopenia/genética , ReinfecçãoRESUMO
A series of 5-nitrofuran-2-yl-thiadiazole linked to different cyclohexyl-2-(phenylamino)acetamides were rationally designed and synthesized. All synthetic compounds were evaluated for their urease inhibitory activity and exhibited good inhibitory potential against urease with IC50 values in the range of 0.94 - 6.78 µM as compared to the standard thiourea (IC50 = 22.50 µM). Compound 8g (IC50 = 0.94 µM) with a thiophene substituent at the R2 position was found to be the most active member of the series. Kinetic studies exhibited that the compound 8g was a non-competitive inhibitor. In silicostudy showed the critical interactions of potent inhibitors with the active site of the enzyme. These newly identified inhibitors of the urease enzyme can serve as leads for further research and development.
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Nitrofuranos , Tiadiazóis , Acetamidas , Biologia Computacional , Inibidores Enzimáticos/química , Cinética , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Tiadiazóis/farmacologia , UreaseRESUMO
Skeletal dysplasias are a heterogeneous group of disorders ranging from mild to lethal skeletal defects. We investigated two unrelated families with individuals presenting with a severe skeletal disorder. In family NMD02, affected individuals had a dysostosis multiplex-like skeletal dysplasia and severe short stature (<-8.5 SD). They manifested increasingly coarse facial features, protruding abdomens, and progressive skeletal changes, reminiscent of mucopolysaccharidosis. The patients gradually lost mobility and the two oldest affected individuals died in their twenties. The affected child in family ID01 had coarse facial features and severe skeletal dysplasia with clinical features similar to mucopolysaccharidosis. She had short stature, craniosynostosis, kyphoscoliosis, and hip-joint subluxation. She died at the age of 5 years. Whole-exome sequencing identified two homozygous variants c.133C>T; p.(Arg45Trp) and c.215dupA; p.(Tyr72Ter), respectively, in the two families, affecting an evolutionary conserved gene TMEM251 (NM_001098621.1). Immunofluorescence and confocal studies using human osteosarcoma cells indicated that TMEM251 is localized to the Golgi complex. However, p.Arg45Trp mutant TMEM251 protein was targeted less efficiently and the localization was punctate. Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes. Our work implicates TMEM251 in the pathogenesis of a novel disorder and suggests its potential function in chondrocyte differentiation.
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Nanismo , Proteínas de Membrana , Osteocondrodisplasias , Animais , Feminino , Humanos , Ratos , Nanismo/genética , Sequenciamento do Exoma , Homozigoto , Proteínas de Membrana/genética , Osteocondrodisplasias/genética , LinhagemRESUMO
BACKGROUND: One of the most common causes of death in the world is coronary artery disease (CAD). Estrogen, the most important early sex hormones in women, plays an important role in the risk reduction of cardiovascular disease (CVD). Expression of estrogen as well as its receptors including estrogen receptor alpha (ER1) and estrogen receptor beta (ER2) might have an association with the severity or the complexity of CAD. Since most articles have focused on the relationship between ER1 gene polymorphism and CAD, in this study, we aimed to evaluate the association of two ER2 gene polymorphisms, rs4986938 (AluI) and rs1256049 (RsaI), with the severity of CAD. METHODS: 148 patients with confirmed CAD who underwent elective percutaneous coronary intervention (PCI) were included in this study. Blood samples were collected before coronary angiography and ER2 gene polymorphisms were analyzed by the PCR-RFLP method. The STNTAX Score (SS), grading system for CAD complexity, was evaluated by an interventional cardiologist who was blinded to other data. RESULTS: 110 men and 38 women were participated in this study. Our results revealed a statistically significant relationship between SS and rs4986938 polymorphism of ER2 in men. In contrast, there was no association between rs1256049 genotypes and SS after performing regression analysis. CONCLUSIONS: Besides to the estrogen level, the genetic variation of its receptors might play an important role in the severity or the complexity of CAD. According to our results, rs4986938 polymorphism of ER2 gene may assert a pivotal role in the severity of CAD in men; however, this assumption needs to be proved in studies with a larger population.
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Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/terapia , Receptor beta de Estrogênio/genética , Intervenção Coronária Percutânea , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Reação em Cadeia da Polimerase , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do TratamentoRESUMO
According to the intrinsic plasticity of stem cells, controlling their fate is a critical issue in cell-based therapies. Recently, a growing body of evidence has suggested that substrate stiffness can affect the fate decisions of various stem cells. Epidermal neural crest stem cells as one of the main neural crest cell derivatives hold great promise for cell therapies due to presenting a high level of plasticity. This study was conducted to define the influence of substrate stiffness on the lineage commitment of these cells. Here, four different polyacrylamide hydrogels with elastic modulus in the range of 0.7-30 kPa were synthesized and coated with collagen and stem cells were seeded on them for 24 hr. The obtained data showed that cells can attach faster to hydrogels compared with culture plate and cells on <1 kPa stiffness show more neuronal-like morphology as they presented several branches and extended longer neurites over time. Moreover, the transcription of actin downregulated on all hydrogels, while the expression of Nestin, Tubulin, and PDGFR-α increased on all of them and SOX-10 and doublecortin gene expression were higher only on <1 kPa. Also, it was revealed that soft hydrogels can enhance the expression of glial cell line-derived neurotrophic factor, neurotrophin-3, and vascular endothelial growth factor in these stem cells. On the basis of the results, these cells can respond to the substrate stiffness in the short term culture and soft hydrogels can alter their morphology and gene expression. These findings suggested that employing proper substrate stiffness might result in cells with more natural profiles similar to the nervous system and superior usefulness in therapeutic applications.
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Técnicas de Cultura de Células/métodos , Meios de Cultura/farmacologia , Módulo de Elasticidade/fisiologia , Crista Neural/citologia , Células-Tronco , Resinas Acrílicas , Animais , Células Cultivadas , Proteína Duplacortina , Expressão Gênica/efeitos dos fármacos , Hidrogéis , Masculino , Ratos , Ratos Wistar , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/fisiologiaRESUMO
BACKGROUND: Gamete cryopreservation is an inseparable part of assisted reproductive technology, and vitrification is an effective approach to the cryopreservation of oocytes. The aim of this study was to investigate vitrification effects on the expression levels of mitochondrial transcription factor A (Tfam) and mitochondrial-encoded cytochrome c oxidase subunit 1 (Cox1) in mouse metaphase II oocytes. METHODS: Oocytes were selected by simple random sampling and distributed amongst five experimental groups (control [n=126], docetaxel [n=132], docetaxel+cryoprotectant agent [CPA] [n=134], docetaxel+vitrification [n=132], and vitrification [n=123]). After the warming process, the oocytes were fertilized and cultured into a 2-cell stage. Then, the effects of vitrification on the expression of the Tfam and Cox1 genes were determined via real-time reverse transcriptase polymerase chain reaction. Each group was compared with the control group. The data were analyzed with ANOVA using GraphPad and SPSS, version 21. RESULTS: A significant decrease was observed in the fertilization rate of each group in comparison with the control group (P=0.001). The rate of 2-cell formation after in vitro fertilization was significantly lower in both vitrification groups (docetaxel+vitrification and vitrification) than in the non-vitrification groups (fresh control and docetaxel) and control group (P=0.001 and P=0.004). The expression level of Cox1 was significantly higher in the vitrification group than in the control group (P=0.01), while it was lower in the docetaxel group than that in the control group (P=0.04). The expression level of the Tfam gene was significantly high in the vitrification group (vitrification+docetaxel) and the non-vitrified group (docetaxel+CPA) in comparison with the control group (P=0.01). CONCLUSION: This study indicated that the vitrification of mouse MII oocytes increased the expression of the Tfam and Cox1 genes.
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Small supernumerary marker chromosomes (sSMCs), or markers, are abnormal chromosomal fragments that can be hereditary or de novo. Despite the importance of sSMCs diagnosis, de novo sSMCs are rarely detected during the prenatal diagnosis process. Usually, prenatally diagnosed de novo sSMCs cannot be correlated with a particular phenotype without knowing their chromosomal origin and content; therefore, molecular cytogenetic techniques are applied to achieve this goal. The present study aimed to characterize an sSMC in a case of Klinefelter syndrome using an in-house microsatellite analysis method and fluorescent in situ hybridization (FISH) technique. Amniotic fluid was collected from a pregnant woman who was considered to have risk factors for trisomy higher than the screening cut-off. Karyotype analysis was followed by the amplification of different microsatellite loci and FISH technique. Karyotype analysis identified a fetus with an extra X chromosome and also an sSMC with unknown identity. Further investigation of the parents showed that the sSMC is de novo. Microsatellite amplification by quantitative fluorescent PCR (QF-PCR) and FISH analysis showed that the sSMC is a derivative of chromosome 18. Eventually, the patient decided to terminate the pregnancy. Here, the first case of the coincidence of sSMC 18 in a Klinefelter fetus is reported.
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Induction of apoptosis or quiescent hepatic stellate cells (HSCs) can be an attractive molecular strategy due to the importance of activation of HSCs during hepatic fibrogenesis. Interleukin-24/melanoma differentiation-associated gene-7 (IL-24/mda-7) is a cytokine that has attracted a great deal of attention in the tumor killing as well as pathophysiology of the diseases. In this study, the Pro-apoptotic and senescence inductive properties of IL-24/mda-7 were assessed in human-derived HSCs. Three plasmids expressing natural mda-7, peptide modified version, mda-7-RGD genes beside a recombinant IL-24 protein, were added or transfected into activated LX-2 cells. Cell viability and the amount of apoptosis were analyzed using MTT and Annexin V staining method, respectively. Hence, the expression levels of apoptotic genes and PPARγ in different groups were also compared by real-time PCR analysis. Furthermore, the senescence effect of IL-24/mda-7 by a ß-galactosidase (SA-ß-gal) senescence assay, was evaluated. The viability assessment showed that pmda-7-RGD had the most significant growth inhibitory effect when compared to the control group, pcDNA3.1 (P = 0.0002). The apoptosis analysis also revealed a significant impact of different mda-7 forms in apoptosis induction. The measuring of cell senescence also indicated that IL-24/mda-7 in plasmid and protein forms exhibited a senescence inductive activity as determined by an increase in PPARγ gene expression and beta-galctosidase activity. In conclusion, our findings demonstrated that both endogenous and soluble forms of IL-24/mda-7 induced apoptosis and senescence in activated LX-2 cells and more importantly, fusion of RGD peptide to this cytokine enhanced these activities. So, RGD-modified IL-24/mda-7 could be a suitable candidate for further molecular therapy of fibrosis.
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Apoptose , Células Estreladas do Fígado/metabolismo , Interleucinas/metabolismo , Oligopeptídeos/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular , Sobrevivência Celular/genética , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Expressão Gênica , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Interleucinas/genética , Interleucinas/farmacologia , Oligopeptídeos/genética , Transdução de Sinais , TransfecçãoRESUMO
BACKGROUND: Breast cancer is the most prevalent cancer and foremost reason of death resulting from malignancy among women worldwide. In recent years, it has been reported that a group of genes named cancer testis genes (CTg) express in adult immune privileged sites and some embryonic tissues. Likewise, it has been demonstrated that CTgs express aberrantly in various tumors and play essential roles in both initiation and development of cancers. In this study, PIWIL2, one member of CTgs, which has an indispensable role in spermatogenesis and tumorigenesis, was examined as an efficient prognostic and diagnostic biomarker in breast cancer. It is worth mentioning that the expression study of PIWIL2 by qPCR on breast cancer samples was performed for the first time, since this approach is much more sensitive than western blot, RT-PCR, and immunohistochemistry. METHODS: To investigate the expression status of PIWIL2 in breast cancer, 72 fresh cancerous and normal adjacent specimens from 44 patients who had undergone surgery in Shahid Faghihi Hospital were used. None of the patients had received chemotherapy. The relationships between the PIWIL2 status and the clinicopathological parameters were ultimately determined. RESULTS: It was ascertained that the expression rates of PIWIL2 in cancerous breast tissues were related to patients' age, tumor stage, tumor size, tumor grade, and lymph node involvement (p < 0.05). CONCLUSIONS: The PIWIL2 gene could be considered as an efficient prognostic biomarker in breast cancer.
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Proteínas Argonautas/genética , Neoplasias da Mama/genética , Adulto , Proteínas Argonautas/fisiologia , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Linfática , Estadiamento de Neoplasias , PrognósticoRESUMO
BACKGROUND: Prostate cancer is the second most prevalent cancer in humans. Also, this is the most common malignancy and the sixth most important cause of death in men worldwide. The most routine diagnostic test for prostate cancer is PSA test which is associated with some limitations like too many false positive results. This study intends to investigate the role of MMP9 and PIWIL2 expression levels as different biomarkers in prostate cancer biopsy specimens. This study is one of the most brilliant studies in the field of prostate cancer research for the first time focusing on the investigation of the role of two different genes in prostate cancer in biopsy specimens and on formalin-fixed paraffin-embedded tissue types in order to detect the progression and prognosis of prostate cancer patients in early stages. METHODS: Seventy formalin-fixed paraffin embedded samples (35 normal and 35 cancerous cases) were selected. Expression levels of PIWIL2 and MMP9 genes were evaluated, using real-time PCR. RESULTS: MMP9 and PIWIL2 expression levels in cancerous tissues were significantly higher than the adjacent normal tissues (p < 0.05). The survival analysis showed a significant correlation between expression level of PIWIL2 and survival rate (p < 0.05), but such correlation was not observed in case of MMP9 (p > 0.05). Higher levels of MMP9 and PIWIL2 expression were strongly related to the Gleason score and age, using Pearson's correlation co- efficient test; however, this kind of association was not evident between prostate specific antigen (PSA) and expression levels of the genes of interest. The expression level of PIWIL2 had a significant correlation with metastasis rate, but this relationship was not seen in the case of MMP9. CONCLUSIONS: The results confirmed the validity of PIWIL2 expression as a valuable prognostic biomarker for early diagnosis of prostate cancer.
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Proteínas Argonautas/genética , Metaloproteinase 9 da Matriz/genética , Neoplasias da Próstata/química , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , RNA Mensageiro/análiseRESUMO
Trisomy 9 is a rare chromosome disorder with high neonatal mortality. It is often seen in mosaic form. Most patients who survive are severely mentally retarded. The main features of this syndrome are "bulbous" nose, microphthalmia, dislocated limbs, and other anomalies of skeletal, cardiac, genitourinary, and central nervous system. Most patients have developmental and cognitive impairment. Patients with mosaicism survive longer than non-mosaics, but it was believed that the degree of mosaicism in lymphocytes or fibroblasts does not associate with survival or degree of impairment. In this report, we present a 2.5-year-old male case of mosaic trisomy 9, to show the wide range of clinical findings in this chromosome disorder. The patient had cardiac anomalies, inguinal hernia, and undescendent testes. He had low-set slightly malformed ears, deeply-set malformed eyes, small palpebral fissures, micrognathia, developmental delay and unilateral optic hypoplasia. The most prominent facial anomaly in this patient was eye anomalies. Cytogenetic analysis with G banding showed karyotype 47XY,+9 in 44% of peripheral lymphocytes examined (47XY,+9[22], 46XY[28]). His parents' karyotypes were normal. Moderate developmental delay, which was detected in this patient shows that the range of motor and cognitive impairment in this chromosomal disorder is quite broad. This fact should be considered in genetic counseling as well as prenatal diagnosis of this chromosomal disorder.
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One of the readily available sources of mesenchymal stem cells (MSCs) is menstrual blood-derived stem cells (Men-SCs), which exhibit characteristics similar to other types of MSCs. This study was performed to determine the growth kinetics, plasticity, and characterization of Men-SCs in women. During spring 2014 in the southern Iranian city of Shiraz, menstrual blood (5 mL) was obtained from 10 women on their third day of menstruation in 2 age groups of 30 to 40 and 40 to 50 years old. Ficoll was used to separate the mononuclear cell fraction. After the Men-SCs were cultured, they were subcultured up to passage 4. Growth behavior and population doubling time were evaluated by seeding 5×10(4) cells into 12- and 24-well culture plates, and the colonies were enumerated. The expression of CD44, CD90, and CD34 was evaluated. The osteogenic potential was assessed by alizarin red staining. The Men-SCs were shown to be plastic adherent and spindle-shaped. Regarding the growth curves in the 12- and 24-well culture plates, it was demonstrated that in the women aged between 30 and 40 years, population doubling time was 55.5 and 62 hours, respectively, while these values in the women aged between 40 and 50 years were 70.4 and 72.4 hours, correspondingly. Positive expression of CD44 and CD90 and negative expression of CD34 were noted. In the osteogenic differentiation medium, the cells differentiated toward osteoblasts. As human Men-SCs are easily collectable without any invasive procedure and are a safe and rapid source of MSCs, they can be a good candidate for stem cell banking and cell transplantation in women.
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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.
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Transtorno do Espectro Autista , Citocinas , Modelos Animais de Doenças , Ácido Valproico , Via de Sinalização Wnt , Peixe-Zebra , Animais , Ácido Valproico/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Transtorno do Espectro Autista/tratamento farmacológico , Citocinas/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Relação Dose-Resposta a DrogaRESUMO
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.
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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.