RESUMO
Implantation of the human embryo begins a critical developmental stage that comprises profound events including axis formation, gastrulation and the emergence of haematopoietic system1,2. Our mechanistic knowledge of this window of human life remains limited due to restricted access to in vivo samples for both technical and ethical reasons3-5. Stem cell models of human embryo have emerged to help unlock the mysteries of this stage6-16. Here we present a genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis that captures the reciprocal codevelopment of embryonic tissue and the extra-embryonic endoderm and mesoderm niche with early haematopoiesis. This model is produced from induced pluripotent stem cells and shows unanticipated self-organizing cellular programmes similar to those that occur in embryogenesis, including the formation of amniotic cavity and bilaminar disc morphologies as well as the generation of an anterior hypoblast pole and posterior domain. The extra-embryonic layer in these embryoids lacks trophoblast and shows advanced multilineage yolk sac tissue-like morphogenesis that harbours a process similar to distinct waves of haematopoiesis, including the emergence of erythroid-, megakaryocyte-, myeloid- and lymphoid-like cells. This model presents an easy-to-use, high-throughput, reproducible and scalable platform to probe multifaceted aspects of human development and blood formation at the early post-implantation stage. It will provide a tractable human-based model for drug testing and disease modelling.
Assuntos
Desenvolvimento Embrionário , Camadas Germinativas , Hematopoese , Saco Vitelino , Humanos , Implantação do Embrião , Endoderma/citologia , Endoderma/embriologia , Camadas Germinativas/citologia , Camadas Germinativas/embriologia , Saco Vitelino/citologia , Saco Vitelino/embriologia , Mesoderma/citologia , Mesoderma/embriologia , Células-Tronco Pluripotentes Induzidas/citologia , Âmnio/citologia , Âmnio/embriologia , Corpos Embrioides/citologia , Linhagem da Célula , Biologia do Desenvolvimento/métodos , Biologia do Desenvolvimento/tendênciasRESUMO
Fibrosis refers to excessive build-up of scar tissue and extracellular matrix components in different organs. In recent years, it has been revealed that different cytokines and chemokines, especially Transforming growth factor beta (TGF-ß) is involved in the pathogenesis of fibrosis. It has been shown that TGF-ß is upregulated in fibrotic tissues, and contributes to fibrosis by mediating pathways that are related to matrix preservation and fibroblasts differentiation. There is no doubt that antioxidants protect against different inflammatory conditions by reversing the effects of nitrogen, oxygen and sulfur-based reactive elements. Oxidative stress has a direct impact on chronic inflammation, and as results, prolonged inflammation ultimately results in fibrosis. Different types of antioxidants, in the forms of vitamins, natural compounds or synthetic ones, have been proven to be beneficial in the protection against fibrotic conditions both in vitro and in vivo. In this study, we reviewed the role of different compounds with antioxidant activity in induction or inhibition of TGF-ß/SMAD signalling pathway, with regard to different fibrotic conditions such as gastro-intestinal fibrosis, cardiac fibrosis, pulmonary fibrosis, skin fibrosis, renal fibrosis and also some rare cases of fibrosis, both in animal models and cell lines.
Assuntos
Fibrose Pulmonar , Fator de Crescimento Transformador beta , Animais , Fator de Crescimento Transformador beta/metabolismo , Antioxidantes/farmacologia , Fibrose , Inflamação , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Smad/metabolismoRESUMO
Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to prescribed medications for these illnesses. However, there is a technology called CRISPR/Cas9, which uses RNA to guide DNA targeting. This technology has revolutionized our ability to manipulate and visualize the genome, leading to advancements in research and treatment development. It can effectively reverse epigenetic alterations that contribute to drug resistance. Some studies focused on health have shown that targeting genes using CRISPR/Cas9 can be challenging when it comes to reducing drug resistance in patients with respiratory disorders. Nevertheless, it is important to acknowledge the limitations of this technology, such as off-target effects, immune system reactions to Cas9, and challenges associated with delivery methods. Despite these limitations, this review aims to provide knowledge about CRISPR/Cas9 genome editing tools and explore how they can help overcome resistance in patients with respiratory disorders. Additionally, this study discusses concerns related to applications of CRISPR and provides an overview of successful clinical trial studies.
Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Humanos , Edição de Genes/métodos , Sistemas CRISPR-Cas/genética , Resistência a Medicamentos/genética , Animais , Transtornos Respiratórios/genética , Transtornos Respiratórios/terapia , Transtornos Respiratórios/tratamento farmacológico , Doenças Respiratórias/genética , Doenças Respiratórias/tratamento farmacológico , Doenças Respiratórias/terapiaRESUMO
BACKGROUND: Calcium signaling has essential roles in the neurodevelopmental processes and pathophysiology of related disorders for instance autism spectrum disorder (ASD). METHODS AND RESULTS: We compared expression of SLC1A1, SLC25A12, RYR2 and ATP2B2, as well as related long non-coding RNAs, namely LINC01231, lnc-SLC25A12, lnc-MTR-1 and LINC00606 in the peripheral blood of patients with ASD with healthy children. Expression of SLC1A1 was lower in ASD samples compared with control samples (Expression ratio (95% CI) 0.24 (0.08-0.77), adjusted P value = 0.01). Contrary, expression of LINC01231 was higher in cases compared with control samples (Expression ratio (95% CI) 25.52 (4.19-154), adjusted P value = 0.0006) and in male cases compared with healthy males (Expression ratio (95% CI) 28.24 (1.91-418), adjusted P value = 0.0009). RYR2 was significantly over-expressed in ASD children compared with control samples (Expression ratio (95% CI) 4.5 (1.16-17.4), adjusted P value = 0.029). Then, we depicted ROC curves for SLC1A1, LINC01231, RYR2 and lnc-SLC25A12 transcripts showing diagnostic power of 0.68, 0.75, 0.67 and 0.59, respectively. CONCLUSION: To sum up, the current study displays possible role of calcium related genes and lncRNAs in the development of ASD.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , RNA Longo não Codificante , Criança , Humanos , Masculino , Sinalização do Cálcio , Canal de Liberação de Cálcio do Receptor de RianodinaRESUMO
The DNA damage response (DDR) is a crucial cellular signaling pathway activated in response to DNA damage, including damage caused by chemotherapy. Chemoresistance, which refers to the resistance of cancer cells to the effects of chemotherapy, poses a significant challenge in cancer treatment. Understanding the relationship between DDR and chemoresistance is vital for devising strategies to overcome this resistance and improve treatment outcomes. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that do not code for proteins but play important roles in various biological processes, including cancer development and chemoresistance. RNA-binding proteins (RBPs) are a group of proteins that bind to RNA molecules and regulate their functions. The interaction between lncRNAs and RBPs has been found to regulate gene expression at the post-transcriptional level, thereby influencing various cellular processes, including DDR signaling pathways. Multiple studies have demonstrated that lncRNAs can interact with RBPs to modulate the expression of genes involved in cancer chemoresistance by impacting DDR signaling pathways. Conversely, RBPs can regulate the expression and function of lncRNAs involved in DDR. Exploring these interactions can provide valuable insights for the development of innovative therapeutic approaches to overcome chemoresistance in cancer patients. This review article aims to summarize recent research on the interaction between lncRNAs and RBPs during cancer chemotherapy, with a specific focus on DDR pathways.
Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Dano ao DNA/genética , Reparo do DNA/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various sources, such as adipose tissue, bone marrow, peripheral blood, inner organs, and neonatal tissues. The regulation of inflammatory cytokines is crucial in inhibiting inflammatory diseases and promoting the presence of anti-inflammatory cytokines for infectious diseases. MSCs have been employed as therapeutic agents for tissue damage, diabetes, autoimmune diseases, and COVID-19 patients. Our research aimed to determine whether live or dead MSCs are more suitable for the treatment of COVID-19 patients. Our findings concluded that dead MSCs, when directly administered to the patient, offer advantages over viable MSCs due to their extended presence and higher levels of immune regulation, such as T-reg, B-reg, and IL-10, compared to live MSCs. Additionally, dead and apoptotic MSCs are likely to be more readily captured by monocytes and macrophages, prolonging their presence compared to live MSCs.
Assuntos
COVID-19 , Doenças Transmissíveis , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Recém-Nascido , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Citocinas , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
BACKGROUND: Alzheimer's disease (AD) is a multifaceted neurological ailment affecting more than 50 million individuals globally, distinguished by a deterioration in memory and cognitive abilities. Investigating neurotrophin growth factors could offer significant contributions to understanding AD progression and prospective therapeutic interventions. METHODS AND RESULTS: The present investigation collected blood samples from 50 patients diagnosed with AD and 50 healthy individuals serving as controls. The mRNA expression levels of neurotrophin growth factors and their receptors were measured using quantitative PCR. A Bayesian regression model was used in the research to assess the relationship between gene expression levels and demographic characteristics such as age and gender. The correlations between variables were analyzed using Spearman correlation coefficients, and the diagnostic potential was assessed using a Receiver Operating Characteristic curve. NTRK2, TrkA, TrkC, and BDNF expression levels were found to be considerably lower (p-value < 0.05) in the blood samples of AD patients compared to the control group. The expression of BDNF exhibited the most substantial decrease in comparison to other neurotrophin growth factors. Correlation analysis indicates a statistically significant positive association between the genes. The ROC analysis showed that BDNF exhibited the greatest Area Under the Curve (AUC) value of 0.76, accompanied by a sensitivity of 70% and specificity of 66%. TrkC, TrkA, and NTRK2 demonstrated considerable diagnostic potential in distinguishing between cases and controls. CONCLUSION: The observed decrease in the expression levels of NTRK2, TrkA, TrkC, and BDNF in AD patients, along with the identified associations between specific genes and their diagnostic capacity, indicate that these expressions have the potential to function as biomarkers for the diagnosis and treatment of AD.
Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Teorema de Bayes , Fator Neurotrófico Derivado do Encéfalo/genética , Receptores Proteína Tirosina Quinases , BiomarcadoresRESUMO
Long non-coding RNAs (lncRNAs) are transcripts with a length of usually more than 200 nucleotides (nt) that have promised functions in varied biological processes. lncRNAs participate in the regulation of differentiation, development, and function of the brain. Thus, their dysregulation might play important roles in the etiology of neurological disorders such as BD. In this study, the expression level of PCAT-1, PCAT-29, and MER11C lncRNAs was evaluated in the blood of BD patients compared to the control group. Peripheral blood mononuclear cells of 50 BD type I patients and 50 healthy individuals were isolated. The RNAs were extracted and cDNA was synthesized. Then, the expression level of the desired lncRNAs was measured through Real-Time PCR. The expression levels of PCAT-29 and MER11C lncRNAs were significantly lower in BD patients compared to controls. However, the expression level of PCAT-1 was not significantly different between these two sets of samples. According to the ROC curve, PCAT-29 and MER11C had significant diagnostic power for the differentiation of BD patients from controls. Taken together, our results indicate dysregulation of two lncRNAs in patients with BD and the possible roles of these lncRNAs in the neuropathology of bipolar disorder.
Assuntos
Transtorno Bipolar , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , Transtorno Bipolar/genética , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos de Casos e Controles , Leucócitos Mononucleares/metabolismoRESUMO
Long non-coding RNAs (lncRNAs) have been recently considered as one of the regulatory mechanisms of the nervous system. Hence, lncRNAs may be considered diagnostic biomarkers for bipolar disorder (BD). We aimed to investigate the expression of RMRP, CTC-487M23.5, and DGCR5 lncRNAs in bipolar patients. The levels of these three lncRNAs were measured in peripheral blood mononuclear cells (PBMCs) of 50 BD patients and 50 healthy subjects by real-time PCR. Moreover, we performed a ROC curve analysis between the gene expression and some clinical features of BD patients. Significant upregulation of RMRP and CTC-487M23.5 and no significant change in levels of DGCR5 was observed in BD individuals compared with controls. Also, we found upregulation of RMRP and downregulation of CTC-487M23.5 and DGCR5 in females with BD. The areas under the ROC curve (AUC) for RMRP and CTC-487M23.5 lncRNAs were 0.80 and 0.61, respectively. There was no significant correlation between the expression of these three lncRNAs and clinical features in PBMCs of BD patients. These results suggest a role for RMRP and CTC-487M23.5 in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these two lncRNAs might be beneficial as potential biomarkers for BD.
Assuntos
Transtorno Bipolar , RNA Longo não Codificante , Feminino , Humanos , Biomarcadores/metabolismo , Transtorno Bipolar/genética , Regulação para Baixo , Leucócitos Mononucleares/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Obesity is a worldwide health problem with an increasing trend. This condition has a significant genetic background. H19 lncRNA has been shown to protect from dietary obesity through decreasing levels of monoallelic genes in brown fat. In the current study, we aimed to find the association between two possibly functional H19 polymorphisms, namely rs217727 and rs2839698 and obesity in Iranian population. These polymorphisms have been shown to affect risk of some obesity-related conditions in different populations. The study included 414 obese cases and 392 controls. Notably, both rs2839698 and rs217727 were associated with obesity in the allelic model as well as all supposed inheritance models. In addition, after adjustment for gender, all P values remained significant. For rs2839698, the OR (95% CI) for T allele vs. C allele was 3.29 (2.67-4.05) (P-value < 0.0001). In the co-dominant model, both TT and CT genotypes were found to confer risk of obesity compared with CC genotype (OR (95% CI)= 14.02 (8.39-23.43) and 9.45 (6.36-14.04), respectively). Similarly, combination of TT and CT genotypes had an OR (95% CI) = 10.32 (7.03-15.17) when compared with CC genotype. For rs217727, the T allele was found to exert a protective effect (OR (95% CI) = 0.6 (0.48-0.75)). Moreover, in the co-dominant model, OR (95% CI) values for TT and TC genotypes vs. CC genotype were 0.23 (0.11-0.46) and 0.65 (0.49-0.87), respectively. Taken together, H19 polymorphisms may affect risk of obesity in Iranian population. It is necessary to conduct functional studies to confirm a causal relationship between the rs217727 and rs2839698 polymorphisms and obesity.
Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Humanos , Irã (Geográfico)/epidemiologia , Genótipo , Obesidade/epidemiologia , Obesidade/genética , Estudos de Casos e ControlesRESUMO
The biosynthesis of novel nanoparticles with varied morphologies, which has good implications for their biological capabilities, has attracted increasing attention in the field of nanotechnology. Bioactive compounds present in the extract of fungi, bacteria, plants and algae are responsible for nanoparticle synthesis. In comparison to other biological resources, brown seaweeds can also be useful to convert metal ions to metal nanoparticles because of the presence of richer bioactive chemicals. Carbohydrates, proteins, polysaccharides, vitamins, enzymes, pigments, and secondary metabolites in brown seaweeds act as natural reducing, capping, and stabilizing agents in the nanoparticle's synthesis. There are around 2000 species of seaweed that dominate marine resources, but only a few have been reported for nanoparticle synthesis. The presence of bioactive chemicals in the biosynthesized metal nanoparticles confers biological activity. The biosynthesized metal and non-metal nanoparticles from brown seaweeds possess different biological activities because of their different physiochemical properties. Compared with terrestrial resources, marine resources are not much explored for nanoparticle synthesis. To confirm their morphology, characterization methods are used, such as absorption spectrophotometer, X-ray diffraction, Fourier transforms infrared spectroscopy, scanning electron microscope, and transmission electron microscopy. This review attempts to include the vital role of brown seaweed in the synthesis of metal and non-metal nanoparticles, as well as the method of synthesis and biological applications such as anticancer, antibacterial, antioxidant, anti-diabetic, and other functions.
RESUMO
Non-functioning pituitary adenomas (NFPAs) are benign lesions in the pituitary gland with important morbidities. In this study, based on a bioinformatics analysis to identify the genes and pathways that display significant differences between tumour tissues of NFPA patients and normal pituitary tissues, we selected lncRNAs related to cAMP and oxidative phosphorylation pathways, namely DNAH17-AS1, LINC00706 and SLC25A5-AS1. Then, we aimed to investigate by means of RT-qPCR, the expression of these lncRNAs along with two other lncRNAs, namely CADM3-AS1 and MIR7-3HG in NFPA samples compared to that in healthy tissues adjacent to the tumours. Transcripts of DNAH17-AS1, LINC00706 and MIR7-3HG were lower in NFPA samples compared with controls (Expression ratios (95% CI) = 0.43 (0.23-0.78), 0.58 (0.35-0.96) and 0.58 (0.35-0.96); p-values = 0.009, 0.025 and 0.036, respectively). AUC values of ROC curves of DNAH17-AS1, LINC00706 and MIR7-3HG were 0.62, 0.61 and 0.62, respectively. Expression of CADM3-AS1 was associated with the gender of patients in a way that it was lower in female patients (p-value = 0.04). The level of SLC25A5-AS1 was lower in subjects with disease duration lower than 1 year (p-value = 0.048). We showed dysregulation of three lncRNAs in NFPA tissues and potentiates these lncRNAs as important regulators of pathogenic events in these tumours.
Assuntos
Neoplasias Hipofisárias , RNA Longo não Codificante , Humanos , Feminino , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fosforilação Oxidativa , Hipófise/metabolismoRESUMO
MIR100HG is a long non-coding RNA (lncRNA) encoded by a locus on chr11:122,028,203-122,556,721. This gene can regulate cell proliferation, apoptosis, cell cycle transition and cell differentiation. MIR100HG was firstly identified through a transcriptome analysis and found to regulate differentiation of human neural stem cells. It is functionally related with a number of signalling pathways such as TGF-ß, Wnt, Hippo and ERK/MAPK signalling pathways. Dysregulation of MIR100HG has been detected in a diversity of cancers in association with clinical outcomes. Moreover, it has a role in the pathophysiology of dilated cardiomyopathy, intervertebral disk degeneration and pulmonary fibrosis. The current study summarizes the role of these lncRNAs in human disorders.
Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , Ciclo Celular , Proliferação de Células/genética , Neoplasias/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , MicroRNAs/genéticaRESUMO
Long non-coding RNAs (lncRNAs) have been shown to be dysregulated in a variety of malignant and non-malignant lesions including non-functioning pituitary adenomas (NFPAs). In the current experimental study, we have selected six lncRNAs, namely MAPKAPK5-AS1, NUTM2B-AS1, ST7-AS1, LIFR-AS1, PXN-AS1 and URB1-AS1 to assess their expression in a cohort of Iranian patients with NFPA. MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 were shown to be over-expressed in NFPA tissues compared with control samples (Expression ratios (95% CI) = 10 (3.94-25.36), 11.22 (4.3-28.8) and 9.33 (4.12-21.12); p values < 0.0001, respectively). The depicted ROC curves showed the AUC values of 0.73, 0.80 and 0.73 for MAPKAPK5-AS1, PXN-AS1 and URB1-AS1, respectively. Relative expression level of PXN-AS1 was associated with tumour subtype (p value = 0.49). Besides, relative expression levels of MAPKAPK5-AS1 and LIFR-AS1 were associated with gender of patients (p values = 0.043 and 0.01, respectively). Cumulatively, the current study indicates the possible role of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in the pathogenesis of NFPAs.
Assuntos
Neoplasias Hipofisárias , RNA Longo não Codificante , Humanos , Regulação para Cima/genética , RNA Longo não Codificante/genética , Neoplasias Hipofisárias/genética , Irã (Geográfico) , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares , PaxilinaRESUMO
Sarcopenia is an elderly disease and is related to frailty and loss of muscle mass (atrophy) of older adults. The exact molecular mechanisms contributing to the pathogenesis of disease are yet to be discovered. In recent years, the role of noncoding RNAs in the pathogenesis of almost every kind of malignant and nonmalignant conditions is pinpointed. Regarding their regulatory function, there have been an increased number of studies on the role of noncoding RNAs in the progress of sarcopenia. In this manuscript, we review the role of microRNAs and long noncoding RNAs in development and progression of disease. We also discuss their potential as therapeutic targets in this condition.
Assuntos
RNA não Traduzido , Sarcopenia , Idoso , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA não Traduzido/genética , Sarcopenia/genéticaRESUMO
BACKGROUND: One of the most common complications in patients with febrile neutropenia, lymphoma, leukemia, and multiple myeloma is a bloodstream infection (BSI). OBJECTIVE: This study aimed to evaluate the antibiotic resistance patterns, virulence factors, biofilm-forming strength, and genetic linkage of Escherichia coli strains isolated from bloodstream infections (BSIs) of leukemia patients. METHODS: The study conducted in Iran from June 2021 to December 2022, isolated 67 E. coli strains from leukemia patients' bloodstream infections in hospitals in two different areas. Several techniques including disk diffusion and broth microdilution were used to identify patterns of antibiotic resistance, microtiter plate assay to measure biofilm formation, and PCR to evaluate the prevalence of different genes such as virulence factors, toxin-antitoxin systems, resistance to ß-lactams and fluoroquinolone antibiotics of E. coli strains. Additionally, the genetic linkage of the isolates was analyzed using the Enterobacterial Repeat Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) method. RESULTS: The results showed that higher frequency of BSI caused by E. coli in man than female patients, and patients with acute leukemia had a higher frequency of BSI. Ampicillin and Amoxicillin-clavulanic acid showed the highest resistance, while Imipenem was identified as a suitable antibiotic for treating BSIs by E. coli. Multidrug-resistant (MDR) phenotypes were present in 22% of the isolates, while 53% of the isolates were ESBL-producing with the blaCTX-M gene as the most frequent ß-lactamase gene. The fluoroquinolone resistance genes qnrB and qnrS were present in 50% and 28% of the isolates, respectively. More than 80% of the isolates showed the ability to form biofilms. The traT gene was more frequent than other virulence genes. The toxin-antitoxin system genes (mazF, ccdAB, and relB) showed a comparable frequency. The genetic diversity was detected in E. coli isolates. CONCLUSION: Our results demonstrate that highly diverse, resistant and pathogenic E. coli clones are circulating among leukemia patients in Iranian hospitals. More attention should be paid to the treatment and management of E. coli bloodstream infections in patients with leukemia.
Assuntos
Infecções por Escherichia coli , Leucemia , Sepse , Sistemas Toxina-Antitoxina , Humanos , Feminino , Escherichia coli , Fatores de Virulência/genética , Irã (Geográfico)/epidemiologia , Infecções por Escherichia coli/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fluoroquinolonas/farmacologia , beta-Lactamases/genética , Farmacorresistência Bacteriana Múltipla/genética , Ligação Genética , Sepse/tratamento farmacológico , Leucemia/tratamento farmacológico , BiofilmesRESUMO
COVID-19 is associated with dysregulation of several genes and signaling pathways. Based on the importance of expression profiling in identification of the pathogenesis of COVID-19 and proposing novel therapies for this disorder, we have employed an in silico approach to find differentially expressed genes between COVID-19 patients and healthy controls and their relevance with cellular functions and signaling pathways. We obtained 630 DEmRNAs, including 486 down-regulated DEGs (such as CCL3 and RSAD2) and 144 up-regulated DEGs (such as RHO and IQCA1L), and 15 DElncRNAs, including 9 down-regulated DElncRNAs (such as PELATON and LINC01506) and 6 up-regulated DElncRNAs (such as AJUBA-DT and FALEC). The PPI network of DEGs showed the presence of a number immune-related genes such as those coding for HLA molecules and interferon regulatory factors. Taken together, these results highlight the importance of immune-related genes and pathways in the pathogenesis of COVID-19 and suggest novel targets for treatment of this disorder.
Assuntos
COVID-19 , Perfilação da Expressão Gênica , Humanos , Perfilação da Expressão Gênica/métodos , Biologia de Sistemas , SARS-CoV-2/genética , Biologia Computacional/métodos , COVID-19/genética , RNA-Seq , Proteínas com Domínio LIMRESUMO
The cytokine known as transforming growth factor (TGF) is essential for cell development, differentiation, and apoptosis in BC. TGF-ß dysregulation can either promote or inhibit tumor development, and it is a key signaling pathway in BC spread. A recently identified family of ncRNAs known as lncRNAs has received a great deal of effort and is an important regulator of many cellular processes, including transcription of genes, chromatin remodeling, progression of the cell cycle, and posttranscriptional processing. Furthermore, both TGF-ß signaling and lncRNAs serve as important early-stage biomarkers for BC diagnosis and prognosis and also play a significant role in BC drug resistance. According to recent studies, lncRNAs can regulate TGF-ß by modulating its cofactors in BC. However, the particular functions of lncRNAs and the TGF-ß pathway in controlling BC progression are not well understood yet. This review explores the lncRNAs' functional properties in BC as tumor suppressors or oncogenes in the regulation of genes, with a focus on dysregulated TGF-ß signaling. Further, we emphasize the functional roles of lncRNAs and TGF-ß pathway in the progression of BC to discover new treatment strategies and better comprehend the fundamental cellular pathways.
Assuntos
Neoplasias , RNA Longo não Codificante , Fator de Crescimento Transformador beta/genética , RNA Longo não Codificante/genética , Transdução de Sinais/genética , Diferenciação Celular , CitocinasRESUMO
miRNA-93 is a member of the miR-106b-25 family and is encoded by a gene on chromosome 7q22.1. They play a role in the etiology of various diseases, including cancer, Parkinson's disease, hepatic injury, osteoarthritis, acute myocardial infarction, atherosclerosis, rheumatoid arthritis, and chronic kidney disease. Different studies have found that this miRNA has opposing roles in the context of cancer. Recently, miRNA-93 has been downregulated in breast cancer, gastric cancer, colorectal cancer, pancreatic cancer, bladder cancer, cervical cancer, and renal cancer. However, miRNA-93 is up-regulated in a wide variety of malignancies, such as lung, colorectal, glioma, prostate, osteosarcoma, and hepatocellular carcinoma. The aim of the current review is to provide an overview of miRNA-93's function in cancer disorder progression and non-cancer disorders, with a focus on dysregulated signaling pathways. We also give an overview of this miRNA's function as a biomarker of prognosis in cancer and emphasize how it contributes to drug resistance based on in vivo, in vitro, and human studies. Video Abstract.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Neoplasias Gástricas , Masculino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Gástricas/genética , Neoplasias Hepáticas/genética , Resistência a Medicamentos , Regulação Neoplásica da Expressão GênicaRESUMO
Natural killer cells (NK cells) are a type of cytotoxic lymphocytes which are involved in innate immunity, alongside with assisting with adaptive immune response. Since they have cytotoxic effects, disruptions in their functionality and development leads to a variety of conditions, whether malignant or non-malignant. The profile and interaction of these non-coding RNAs and NK cells in different conditions is extensively studied, and it is now approved that if dysregulated, non-coding RNAs have detrimental effects on NK cell activity and can contribute to the pathogenesis of diverse disorders. In this review, we aim at a thorough inspection on the role of different non-coding RNAs on the activity and development of NK cells, in a broad spectrum of conditions, including blood-related disorders, viral infections, neurological diseases, gastrointestinal disorders, lung disorders, reproductive system conditions and other types of maladies, alongside with providing insight to the future non-coding RNA-NK cell studies.