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INTRODUCTION: Chronic wounds are debilitating complications of diabetes mellitus. The present study was conducted to investigate the effect of the hair follicle stem cells (HFSCs) by polycaprolactone scaffold on the healing of incisional cutaneous wounds on streptozotocin-induced diabetic male rats. METHODS: The wound model was obtained by a biopsy punch of the skin of the animals' back. The animals were randomly divided into five groups as follows: (1) Sham (nondiabetic, not treated), (2) Control (diabetic, not treated), (3) Scaffold (diabetic, treated with polycaprolactone nanofiber scaffold), (4) HFSCs (diabetic, treated with HFSCs), and (5) Scaffold + HFSCs (diabetic, treated with combination of Scaffold and HFSCs). The wounds were photographed in the course of the treatment and their healing rate was assessed. The samples were collected from the wound sites 7, 14, and 28 d after their development. Angiogenesis was surveyed by examining messenger RNA expression and the protein synthesis levels of vascular endothelial growth factor receptor 2 (VEGFR2) and platelet/endothelial cell adhesion molecule-1/cluster of differentiation 31. The histological changes were investigated using hematoxylin and eosin and Masson's trichrome staining. Furthermore, the wound breaking strength was measured on the 28th day by tensiometry. RESULTS: The application of the VEGFR2 as a substrate promotes the expression of CD31 in HFSCs and Scaffold + HFSCs groups compared to controls (P < 0.0001). HFSCs and scaffold also rescue the diabetes-induced dysfunction as assessed based on the parameters, such as viability, proliferation, colony formation, cellular adhesion, and chemotactic migration. HFSCs augment the levels of VEGFR2 and promote the restoration of the wound healing in diabetic groups. Furthermore, the maximum biomechanical stress significantly increased in the experimental diabetic groups (Scaffold: 1.38 ± 0.09, HFSCs: 2.13 ± 0.8, Scaffold + HFSCs: 2.38 ± 0.11) compared to the diabetes control group (1.16 ± 0.12). Using of HFSCs and scaffold on diabetic wounds leads to an accelerated wound closure, notably. CONCLUSIONS: Thus, the current data showed that HFSCs and scaffold form excellent biomaterial in the treatment of diabetic wounds.
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Diabetes Mellitus , Herida Quirúrgica , Animales , Masculino , Ratas , Folículo Piloso , Células Madre , Factor A de Crecimiento Endotelial Vascular/genética , Cicatrización de HeridasRESUMEN
Diabetes is associated with numerous complications, such as diabetic skin wounds or ulcerations. The aim of this study was to evaluate experimentally the effectiveness of applying polycaprolactone (PCL)-gelatin scaffold, with or without rat CD93 hematopoietic stem cells (HSCs), in diabetic wound healing in a rat model. CD93 HSCs were aseptically isolated from rat bone marrow using fluorescent activated cell sorting (FACS) method and FACS-SORTER. A total of 25 Wistar rats were divided into five groups including Group I (sham, nondiabetic, and wound covered only with sterile dressing), II (control, diabetic rat), III (CD93 HSCs alone), IV (PCL-gelatin scaffold), and V (CD93 HSCs+PCL-gelatin scaffold). Animals were killed on Days 7, 14, or 28 posttreatment and histological sections were blindly evaluated by two expert pathologists. Death-associated protein kinase 1 (DAPK-1) gene and vesicular endothelial growth factors (VEGF) protein expression were evaluated using reverse transcription-polymerase chain reaction and western blot, respectively. The thickest and the thinnest epidermises microscopically were belonged to CD93+HSCs+scaffold and the control group, respectively. The growth rate of the epidermis and adnexal epithelia was the highest in both the cell and cell+scaffold groups. Evaluation of the protein expression level of VEGF indicated that the expression levels of this growth factor were the most on Day 7 posttreatment in sham, HSCs alone, and HSCs cell+scaffold groups. While the lowest expression levels of this growth factor was detected in the control and scaffold groups. The gene expression level of DAPK-1 on Day 7 posttreatment was higher than that of the Day 14 posttreatment in all groups. The highest and lowest gene expression levels of DAPK-1 belonged to control and sham groups, respectively. According to our findings, CD93 HSCs offer new prospects for the treatment of diabetic ulcers and concomitant application of these cells with PCL-gelatin nanofiber scaffold significantly improves diabetic wound treatment.
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Proteínas Quinasas Asociadas a Muerte Celular/genética , Complicaciones de la Diabetes/genética , Subfamília D de Receptores Similares a Lectina de las Células NK/genética , Factor A de Crecimiento Endotelial Vascular/genética , Cicatrización de Heridas/genética , Animales , Complicaciones de la Diabetes/patología , Complicaciones de la Diabetes/terapia , Gelatina/química , Gelatina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/metabolismo , Humanos , Poliésteres/química , Poliésteres/farmacología , Ratas , Andamios del Tejido/químicaRESUMEN
Tuberculosis has been declared as a global emergency. Latent tuberculosis infection (LTBI) is a state in which host immunity cannot completely eradicate Mycobacterium tuberculosis. Cigarette smoke increases the risk of respiratory infections, such a TB, as it has adverse effects on respiratory immune function. In this cross-sectional study, which was performed from 2016 to 2017, 31 patients with newly diagnosed lung cancer, 63 Chronic obstructive pulmonary disease (COPD), 46 with problems in respiratory system, and 40 healthy subjects were studied. Demographic data of all subjects were recorded via a questionnaire. IGRAs (Interferon-γ release assays) were used to determine LTBI. We showed that smoking has significant odds ratio for COPD patients (OR: 4.58, 95% CI: 1.93-10.87). Also, the concordance of smoking with COPD (OR: 22, 95% CI: 2.7-179.2), lung cancer (OR: 10, 95% CI: 1.03-97), and other respiratory diseases (OR: 4.54, 95% CI: 1.93-10.87) is a significant risk factor for the presence of LTBI whereas the existence of LTBI in the study groups did not show any significant odds ratio. This study is the first to analyze the relationship between smoking in patients with respiratory diseases and LTBI susceptibility in Iran by IGRAs, which proposes cigarette smoking as a powerful risk factor for LTBI.
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Susceptibilidad a Enfermedades , Tuberculosis Latente , Fumar/efectos adversos , Anciano , Estudios Transversales , Femenino , Humanos , Interferón gamma/análisis , Ensayos de Liberación de Interferón gamma , Irán/epidemiología , Tuberculosis Latente/epidemiología , Tuberculosis Latente/inmunología , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Sistema Respiratorio/inmunología , Sistema Respiratorio/patología , Factores de RiesgoRESUMEN
Common variable immunodeficiency (CVID), a clinically symptomatic primary immunodeficiency disease (PID), is characterized by hypogammaglobulinemia leading to recurrent infections and various complications. Recently, some defects in the signaling of TLRs have been identified in CVID patients which led us to investigate the expression of TLR4 and 9 negative regulatory molecules and their upregulation status following their activation. Using TaqMan real-time PCR, SOCS1, TNFAIP3, RFN216, and IRAK-M transcripts among peripheral blood mononuclear cells (PBMCs) were measured with/without TLR4 and 9 activations. TLR4 and 9 were activated by lipopolysaccharide (LPS) and unmethylated CpG-oligodeoxynucleotide (CpG-ODN), respectively. Production of IFN-α and TNF-α cytokines, as a part of the functional response of mentioned TLRs, was also measured using ELISA. Deficient transcripts of IRAK-M and TNFAIP3 in unstimulated PBMCs and lower production of TNF-α and IFN-α after treatments were observed. Upregulation of RFN216 and TNFAIP3 after TLR9 activation was abnormal compared to healthy individuals. Significant correlations were found between abnormal IRAK-M and TNFAIP3 transcripts, and lymphadenopathy and inflammatory scenarios in patients, respectively. It seems that the transcriptional status of some negative regulatory molecules is disturbed in CVID patients, and this could be caused by the underlying pathogenesis of CVID and could involve complications like autoimmunity and inflammatory responses.
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Inmunodeficiencia Variable Común/genética , Redes Reguladoras de Genes , Receptor Toll-Like 4/genética , Receptor Toll-Like 9/genética , Adolescente , Adulto , Células Cultivadas , Inmunodeficiencia Variable Común/inmunología , Citocinas/genética , Citocinas/metabolismo , Femenino , Humanos , Quinasas Asociadas a Receptores de Interleucina-1/genética , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Masculino , Monocitos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Proteína 1 Supresora de la Señalización de Citocinas/genética , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 9/metabolismo , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Mucopolysaccharidosis VI is a rare autosomal recessive disorder caused by the deficiency of enzyme Arylsulfatase B. The enzyme deficiency leads to the accumulation of dermatan sulfate in connective tissue which causes manifestations related to MPS VI. Up to now, three different disease causing variants are reported in Iranian patients. In this study, we scanned ARSB gene of 13 Iranian patients from 12 families in whom all parents were consanguineous and from the same ethnicity except one family that were not consanguineous but co-ethnic. We found six not previously reported disease causing variants. We extracted DNA from peripheral blood samples of patients that were previously confirmed as MPS VI by clinical, biochemical and enzymatic assays including berry-spot test and fluorimetry, followed by PCR and direct sequencing. Computational approaches were used to analyze novel variants in terms of their impact on the protein structure. 11 disease causing variants and 15 polymorphisms were found. Six disease causing variants were novel and five were previously reported of which three were in Iranian population. Four of patients, who were unrelated, two by two had the same disease causing variant and polymorphisms, which indicates a possible founder effect. Our study also implicates genotype-phenotype correlation. Computational structural modeling indicated these disease causing variants might affect structural stability and function of the protein. Data of this study confirms the existence of mutational heterogeneity in the ARSB between Iranian patients. Disease causing variants with high frequency can be used in the prenatal diagnosis and genetic counseling. Also, the existence of the same variants and polymorphisms in some of the unrelated patients indicates a possible founder effect.
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Mucopolisacaridosis VI/genética , Mutación , N-Acetilgalactosamina-4-Sulfatasa/genética , Niño , Preescolar , ADN/genética , Análisis Mutacional de ADN , Exones , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Variación Genética/genética , Humanos , Lactante , Irán , Masculino , Mucopolisacaridosis VI/enzimología , Mucopolisacaridosis VI/metabolismo , N-Acetilgalactosamina-4-Sulfatasa/metabolismo , Linaje , Polimorfismo Genético/genéticaRESUMEN
BACKGROUND AND AIM: Leukocyte adhesion deficiency type 1 is a rare, autosomal recessive disorder that results from mutations in the ITGB2 gene. This gene encodes the CD18 subunit of ß2 integrin leukocyte adhesion cell molecules. Leukocyte adhesion deficiency type 1 is characterized by recurrent bacterial infections, impaired wound healing, inadequate pus formation, and delayed separation of the umbilical cord. MATERIALS AND METHODS: Blood samples were taken from 13 patients after written consent had been obtained. Genomic DNA was extracted, and ITGB2 exons and exon-intron boundaries were amplified by polymerase chain reaction. The products were examined by Sanger sequencing. RESULTS: In this study, 8 different previously reported mutations (intron7+1G>A, c.715G>A, c.1777 C>T, c.843del C, c.1768T>C, c.1821C>A, Intron7+1G>A, c.1885G>A) and 2 novel mutations (c.1821C>A; p.Tyr607Ter and c.1822C>T; p.Gln608Ter) were found. CONCLUSIONS: c.1821C>A (p.Tyr607Ter) and c.1822C>T (p.Gln608Ter) mutations should be included in the panel of carrier detection and prenatal diagnosis.
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Antígenos CD18/genética , Pruebas Genéticas , Síndrome de Deficiencia de Adhesión del Leucocito/genética , Mutación Missense , Sustitución de Aminoácidos , Análisis Mutacional de ADN , Femenino , Humanos , Lactante , Recién Nacido , Irán , Masculino , Estudios RetrospectivosRESUMEN
Background Quantitative fluorescent polymerase chain reaction (QF-PCR) technique is a rapid prenatal aneuploidy detection method. This method can diagnose abnormality in chromosome 13, 18, 21, X and Y. Karyotyping is a technique in which, by the process of pairing and painting, all the chromosomes of an organism are displayed under a microscope. In the present study, a statistical comparison was made between karyotyping and QF-PCR for prenatal diagnosis. Methods A total of 270 samples were tested for QF-PCR and the results were compared with karyotyping. We also investigated heterozygosity of short tandem repeat (STR) markers by QF-PCR. Deoxyribonucleic acid (DNA) samples (n = 270) were extracted from amniotic fluid (AF) cells. After PCR amplifications, analysis was performed using GeneMarker. A Devyser QF-PCR kit containing 26 primers was used to estimate the observed heterozygosity of STR markers located on chromosome 13, 18, 21, X and Y. Results The results of karyotyping and QF-PCR were as follows: trisomy 13 (one case), trisomy 18 (five cases), trisomy 21 (five cases) and triploidy (one case). Chromosomal rearrangements and mosaicisms were not detected by QF-PCR but were detected by karyotyping. Maternal cell contamination (MCC) made the karyotyping fail but not the QF-PCR. Conclusion The QF-PCR method is especially important because it is fast, accurate, low cost and has a short turnaround time. This method will avoid ambiguity of karyotype results and parental anxiety. It will also shorten clinical management for high-risk families.
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Aneuploidia , Trastornos de los Cromosomas , Cariotipificación/métodos , Reacción en Cadena de la Polimerasa/métodos , Adulto , Líquido Amniótico/citología , Trastornos de los Cromosomas/clasificación , Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/epidemiología , Trastornos de los Cromosomas/genética , Investigación sobre la Eficacia Comparativa , Femenino , Humanos , Citometría de Imagen/métodos , Irán/epidemiología , Embarazo , Reproducibilidad de los ResultadosRESUMEN
Hereditary ataxias (HA) are a group of inherited neurological disorders caused by changes in genes. At least 115 different mutations in the senataxin (SETX) gene causing ataxia have been identified. There are no reports of any SETX gene mutation among the Iranian population. Here we report on two cases with homozygous and heterozygous mutations in which one patient was affected by HA with oculomotor apraxia type 2, and the other was a carrier of the disorder. In 2016, the affected patient was referred to the Biogene Medical and Genetic Laboratory (Tehran, Iran) suffering from imbalance and tremor of both head and body. The coding regions of 18 genes, including the SETX gene, were screened. The target regions were captured using the NimbleGen chip followed by next-generation sequencing (NGS) technology on the Illumina Hiseq2500 platform. NGS, a DNA sequencing technology, has greatly increased the ability to identify new causes of ataxia; a useful tool for the prevention of primary manifestations and treatment of affected patients. In the present study, a novel mutation in the SETX gene has been identified.
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Chronic granulomatous disease (CGD) is an inherited disease of the innate immune system that results from defects in 1 of the 5 subunits of nicotinamide adenine dinucleotide phosphate oxidase complex and leads to life-threatening infections with granuloma formation. During 3 years of study, we recognized 10 male patients with X-linked CGD from a tertiary referral center for immune deficiencies in Iran. The CGD patients were diagnosed according to clinical features and biochemical tests, including nitroblue tetrazolium and dihydrorhodamine-1, 2, 3 tests, performed on patients and their mothers. In all patients, Western blot analysis showed a gp91 phenotype. Mutation screening by single strand conformation polymorphism and multiplex ligation-dependent probe amplification analysis of the CYBB gene encoding gp91, followed by sequencing, showed 9 different mutations, 4 of them novel as far as we know.
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Familia , Enfermedad Granulomatosa Crónica/genética , Mutación , NADPH Oxidasa 2/genética , Niño , Preescolar , Humanos , Lactante , Irán , MasculinoRESUMEN
Gene therapy is based on the principle of the genetic manipulation of DNA or RNA for treating and preventing human diseases. The clustered regularly interspaced short palindromic repeats/CRISPR associated nuclease9 (CRISPR/Cas9) system, derived from the acquired immune system in bacteria and archaea, has provided a new tool for accurate manipulation of genomic sequence to attain a therapeutic result. The advantage of CRISPR which made it an easy and flexible tool for diverse genome editing purposes is that a single protein (Cas9) complex with 2 short RNA sequences, function as a site-specific endonuclease. Recently, application of CRISPR/Cas9 system has become popular for therapeutic aims such as gene therapy. In this article, we review the fundamental mechanisms of CRISPR-Cas9 function and summarize preclinical CRISPR-mediated gene therapy reports on a wide variety of disorders.
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Sistemas CRISPR-Cas , Edición Génica , Terapia Genética , HumanosRESUMEN
Amyloid-ß (Aß) as a crucial factor in pathogenesis of Alzheimer's disease (AD) is derived from amyloid precursor protein (APP) through a proteolytic process catalyzing by ß- and γ-secretase-in amyloidogenesis pathway. Products of α-secretase cleavage also have protective effects against Aß toxicity. According to existing evidences, microRNAs (miRNAs) show a unique pattern of expression in AD. Moreover, miRNAs regulatory effects on expression of secretases and their main components have been demonstrated in AD. The miRNAs levels may be changed in preclinical conditions and may be considered as diagnostic biomarkers in AD. Therefore, in this paper, we review the miRNAs involved in APP cleavage pathways and the formation of Aß in order to evaluate the potential diagnostic biomarkers in AD.
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Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , MicroARNs/metabolismo , Animales , Biomarcadores/metabolismo , HumanosRESUMEN
BACKGROUND: Oxidative degradation of human recombinant erythropoietin (hrEPO) may occur in manufacturing process or therapeutic applications. This unfavorable alteration may render EPO inefficient or inactive. We investigated the effect of methionine/54 oxidative changes on the amino acid sequences, glycoform distribution and biological activity of hrEPO. METHODS: Mass spectrometry was applied to verify the sequence and determine the methionine oxidation level of hrEPO. Isoform distribution was studied by capillary zone electrophoresis method. In vivo normocythemic mice assay was used to assess the biological activity of three different batches (A, B, and C) of the proteins. RESULTS: Nano-LC/ESI/MS/MS data analyses confirmed the amino acid sequences of all samples. The calculated area percent of three isoforms (2-4 of the 8 obtained isoforms) were decreased in samples of C, B, and A with 27.3, 16.7, and 6.8% of oxidation, respectively. Specific activities were estimated as 53671.54, 95826.47, and 112994.93 mg/mL for the samples of A, B, and C, respectively. CONCLUSION: The observed decrease in hrEPO biological activity, caused by increasing methionine oxidation levels, was rather independent of its amino acid structure and mainly associated with the higher contents of acidic isoforms.
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Eritropoyetina/química , Metionina/análisis , Proteínas Recombinantes/química , Secuencia de Aminoácidos , Animales , Cromatografía Liquida , Electroforesis Capilar , Eritropoyetina/metabolismo , Humanos , Metionina/metabolismo , Ratones , Oxidación-Reducción , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes/metabolismo , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en TándemRESUMEN
Different biological tools for targeted genome engineering have recently appeared and these include tools like meganucleases, zinc-finger nucleases and newer technologies including TALENs and CRISPR/Cas systems. transcription activator-like effector nucleases (TALENs) have greatly improved genome editing efficiency by making site-specific DNA double-strand breaks. Several studies have shown the prominence of TALENs in comparison to the meganucleases and zinc-finger nucleases. The most important feature of TALENs that makes them suitable tools for targeted genome editing is the modularity of central repeat domains, meaning that they can be designed to recognize any desirable DNA sequence. In this review, we present a comprehensive and concise description of TALENs technology developments for targeted genome surgery with to the point description and comparison of other tools.
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Ingeniería Genética , Terapia Genética , Genética Médica , Genómica , Animales , Desoxirribonucleasas , Humanos , Ratones , Dedos de ZincRESUMEN
Among the myriad of nanoparticles, silica nanoparticles (SiO2NPs) have gained significant attention since they are extensively produced and used across several kinds of industries. Because of its widespread usage, there has been increasing concern about the potential health effects. This study aims to evaluate the effects of SiO2NPs on Interleukin-6 (IL-6) gene expression in human lung epithelial cell lines (A549). In this study, A549 cells were exposed to SiO2NPs at concentrations of 0, 1, 10, 50, 100, and 200 µg/mL for 24 and 48 h. The IL-6 gene expression was assessed using Real-Time RT-PCR. Additionally, the impact of SiO2NPs on the viability of A549 cells was determined by MTT assay. Statistical analysis was performed using GraphPad Prism software 8.0. MTT assay results indicated a concentration-dependent impact on cell survival. After 24 h, survival decreased from 80 to 68% (1-100 µg/mL), rising to 77% at higher concentrations. After 48 h, survival dropped from 97 to 80%, decreasing to 90% at higher concentrations. RT-PCR showed a dose-response relationship in cellular toxicity up to 10 µg/mL. At higher concentrations, there was increased IL-6 gene expression, mitigating SiO2NP-induced cytotoxic effects. The study shows that the viability and proliferation of A549 cells are impacted by different SiO2NPs concentrations. There may be a potential correlation between IL-6 gene expression reduction and a mechanism linked to cellular toxicity. However, at higher concentrations, an unknown mechanism increases IL-6 gene expression, reducing SiO2NPs' cytotoxic effects. These effects are concentration-dependent and not influenced by exposure times. Further investigation is recommended to determine this mechanism's nature and implications, particularly in cancer research.
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Supervivencia Celular , Interleucina-6 , Nanopartículas , Dióxido de Silicio , Humanos , Dióxido de Silicio/toxicidad , Dióxido de Silicio/química , Células A549 , Nanopartículas/toxicidad , Nanopartículas/química , Interleucina-6/metabolismo , Interleucina-6/genética , Supervivencia Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacosRESUMEN
Breast cancer (BC) is the second most common malignancy worldwide. ADGRL4, as a modulator of angiogenesis, undergoes various epigenetic modifications affecting its biological functions. In this study, we aimed to assess ADGRL4 promoter methylation status and its expression levels in primary breast tumors and to evaluate its potency as a plausible prognostic biomarker in BC. Furthermore, we evaluated the effect of melatonin on ADGRL4 expression and viability of BC cells in vitro. One hundred breast tumor tissue samples and adjacent non-tumor tissues were collected, followed by DNA isolation, bisulfite conversion, qRT-PCR, qMSP assay, and immunoblotting. In addition, four BC cell lines were treated with melatonin and subjected to ADGRL4 expression analysis and apoptosis assay. We found a significant correlation between ADGRL4 expression levels and HER2 status and stage of disease (P < 0.05). We observed a substantial attenuation in ADGRL4 promoter methylation in tumor samples compared to marginal non-tumor samples. A significantly lower expression of ADGRL4 was detected in two BC cell lines in the presence of melatonin. MCF-7 and BT474 melatonin-treated cell lines showed a significantly higher number of apoptotic cells than non-treated cells (P < 0.0001). Based on the receiver operating characteristic (ROC) curve analysis, ADGRL4 expression and ADGRL4 promoter methylation status showed moderate prognostic value. We found that melatonin has anti-cancer effects on BC cells. In addition, ADGRL4 expression can potentially be used as a prognostic biomarker in BC.
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Occupational health must be strictly considered in industries particularly in nanoparticle factories where workers were exposed to different types of chemicals. We measured the serum levels of inflammatory cytokines in workers who developed skin lesions after exposure to silver and silica nanoparticles. Using a questionnaire in this cross-sectional study, we identified 110 workers in nanoparticle industries who were exposed to silver and silica nanoparticles. We also included 40 healthy subjects as controls from the administrative department of the same factories who were not exposed to nanoparticles. Peripheral blood samples used to measure the mRNA levels of inflammatory cytokines by qRT-PCR. In comparison with the control group, the workers who developed skin lesions had significantly higher levels of interleukin IL4, IL6, IL8, and TNF-α, particularly after two or three decades of exposure to silver and silica nanoparticles. Participants who were exposed to silver had higher levels of IL6 and IL8 compared with those who were exposed to silica. Necessary measures must be considered to protect workers in nanoparticle industries against the potential toxic effects of these compounds. Our network pharmacology study suggests corresponding biochemical pathways for these disorders.
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Nanopartículas , Exposición Profesional , Humanos , Dióxido de Silicio/toxicidad , Plata , Interleucina-6 , Estudios Transversales , Interleucina-8 , Exposición Profesional/efectos adversos , Citocinas/genética , Expresión GénicaRESUMEN
Aim: MicroRNAs can be regarded as biomarkers for gastric cancer (GC) diagnosis in the early stages. This study assesses the expression levels of miR-362-3p, miR-362-5p and miR-363-5p as potential biomarkers for GC.Materials & methods: The expression levels of the miRNAs in 90 pairs of GC and adjacent normal tissue samples were analyzed by quantitative real-time reverse transcription PCR (qRT-PCR) and some bioinformatics tools were utilized for analyzing the target genes and possible molecular pathways in which these miRNAs participate.Results & conclusion: There was a significant overexpression of the miRNAs in GC cells and an outstanding correlation between their overexpression with some clinicopathological features of the patients.
[Box: see text].
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Biomarcadores de Tumor , MicroARNs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , MicroARNs/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Anciano , AdultoRESUMEN
Lung adenocarcinoma is one of the leading causes of cancer-related mortality globally. Various treatment approaches and drugs had little influence on overall survival; thus, new drugs and treatment strategies are needed. Drug repositioning (repurposing) seems a favorable approach considering that developing new drugs needs much more time and costs. We performed a meta-analysis on 6 microarray datasets to obtain the main genes with significantly altered expression in lung adenocarcinoma. Following that, we found major gene clusters and hub genes. We assessed their enrichment in biological pathways to get insight into the underlying biological process involved in lung adenocarcinoma pathogenesis. The L1000 database was explored for drug perturbations that might reverse the expression of differentially expressed genes in lung adenocarcinoma. We evaluated the potential drug combinations that interact the most with hub genes and hence have the most potential to reverse the disease process. A total of 2148 differentially expressed genes were identified. Six main gene clusters and 27 significant hub genes mainly involved in cell cycle regulation have been identified. By assessing the interaction between 3 drugs and hub genes and information gained from previous clinical investigations, we suggested the three possible repurposed drug combinations, Vorinostat - Dorsomorphin, PP-110 - Dorsomorphin, and Puromycin - Vorinostat with a high chance of success in clinical trials.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Reposicionamiento de Medicamentos , Vorinostat , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Combinación de Medicamentos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genéticaRESUMEN
Multiple Sclerosis (MS) is a multifactorial, neurodegenerative, and inflammatory demyelination disease with incomplete remyelination in the CNS. It would be more informative to reveal the underlying molecular mechanisms of MS. Molecular mechanisms involving epigenetic changes play a pivotal role in this disease. Epigenetic changes impact gene expression without altering the underlying DNA sequence. The main epigenetic modifications that play a key role in the regulation of gene expression principally include DNA methylation, histone modifications, and microRNA- associated post-transcriptional gene silencing. In this review, we summarize the dynamics of epigenetic changes and their relation to environmental risk factors in MS pathogenesis. Studies suggest that epigenetic changes have a role in the development of MS and environmental risk factors, such as vitamin D, smoking, and Epstein-Barr virus infection seem to influence the development and susceptibility to MS. Investigating epigenetic and environmental factors can provide new opportunities for the molecular basis of the diseases, which shows complicated pathogenesis. Epigenetic research has the potential to complete our understanding of MS initiation and progression. Increased understanding of MS molecular pathways leads to new insights into potential MS therapies. However, there is a need for in vivo evaluation of the role of epigenetic factors in MS therapy. It would be more valuable to indicate the role of various epigenetic factors in MS.
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Infecciones por Virus de Epstein-Barr , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/genética , Esclerosis Múltiple/terapia , Infecciones por Virus de Epstein-Barr/genética , Herpesvirus Humano 4 , Epigénesis Genética , Metilación de ADNRESUMEN
Autophagy is a significant catabolic procedure that increases in stressful conditions. This mechanism is mostly triggered after damage to the organelles, the presence of unnatural proteins, and nutrient recycling in reaction to these stresses. One of the key points in this article is that cleaning and preserving damaged organelles and accumulated molecules through autophagy in normal cells helps prevent cancer. Since dysfunction of autophagy is associated with various diseases, including cancer, it has a dual function in tumor suppression and expansion. It has newly become clear that the regulation of autophagy can be used for the treatment of breast cancer, which has a promising effect of increasing the efficiency of anticancer treatment in a tissue- and cell-type-specific manner by affecting the fundamental molecular mechanisms. Regulation of autophagy and its function in tumorigenesis is a vital part of modern anticancer techniques. This study discusses the current advances related to the mechanisms that describe essential modulators of autophagy involved in the metastasis of cancers and the development of new breast cancer treatments.