RESUMEN
Attention deficit hyperactivity disorder (ADHD) is a clinically and genetically heterogeneous neurodevelopmental syndrome characterized by behavioral appearances such as impulsivity, inattention, and hyperactivity. The prevalence of ADHD is high in childhood when compared to adults. ADHD has been significantly advanced by genetic research over the past 25 years. However, it is logically conceivable that both genetic and/or non-genetic factors, such as postnatal environmental and social influences, are associated with ADHD phenotype in Arab populations. While genetic influences are strongly linked with the etiology of ADHD, it remains obscure how consanguinity which is an underlying factor for many genetic diseases, contributes to ADHD subtypes. Arabian Gulf Nations have one the highest rates of consanguineous marriages, and consanguinity plays an important contributing factor in many genetic diseases that exist in higher percentages in Arabian Gulf Nations. Therefore, the current review aims to shed light on the genetic variants associated with ADHD subtypes in Arabian Gulf nations and Saudi Arabia in particular. It also focuses on the symptoms and the diagnosis of ADHD before turning to the neuropsychological pathways and subgroups of ADHD. The impact of a consanguinity-based understanding of the ADHD subtype will help to understand the genetic variability of the Arabian Gulf population in comparison with the other parts of the world and will provide novel information to develop new avenues for future research in ADHD.
RESUMEN
INTRODUCTION: Papillary thyroid carcinoma accounts for the most common type of thyroid cancer of well-differentiated type. Papillary thyroid carcinoma is featured by biologically low-grade and less aggressive tumors with a survival rate of 10 years in most of the diagnosed cases. Papillary thyroid carcinoma can be presented with the involvement of cervical lymph nodes in about 50% of the patients, yet distant spread is very uncommon. CASE PRESENTATION: Herein, we discuss a Saudi male patient in his early 50s with a history of papillary thyroid carcinoma who presented to the emergency department complaining of shortness of breath and a radiological finding of hydrothorax. Cytologic examination together with immune-histochemical staining and molecular studies of pleural effusion aspiration concluded the definitive diagnosis of metastatic papillary thyroid carcinoma in the pleural space. CONCLUSIONS: Papillary thyroid carcinoma seldom causes metastatic niches in the pleural space; this is a rare clinical presentation, nevertheless, a differential diagnosis of thyroid metastasis needs to be excluded. A definitive diagnosis of metastatic papillary thyroid carcinoma can be made using clinical presentation, cytologic examination, immunohistochemical investigation, and molecular testing. The most common mutation found in papillary thyroid carcinoma cases is the V600E mutation found in the BRAF gene, yet these patients have a relatively low probability of cancer recurrence. Patients with papillary thyroid carcinoma who have the BRAF mutation frequently experience metastases and relapses of the disease after the cancer has progressed aggressively. To help with therapy planning and the introduction of BRAF inhibitors, genetic testing for BRAF mutation may therefore prove to be a useful tool, especially in cases of aggressive subtypes of TC.
Asunto(s)
Carcinoma Papilar , Derrame Pleural , Neoplasias de la Tiroides , Humanos , Masculino , Carcinoma Papilar/diagnóstico , Mutación , Recurrencia Local de Neoplasia , Proteínas Proto-Oncogénicas B-raf/genética , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Persona de Mediana EdadRESUMEN
Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1ß (IL-1ß), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.
Asunto(s)
Lesión Renal Aguda , Isoflavonas , Rabdomiólisis , Ratas , Masculino , Animales , Glicerol/toxicidad , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Riñón , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Estrés Oxidativo , Isoflavonas/farmacología , Rabdomiólisis/inducido químicamente , Rabdomiólisis/complicaciones , Rabdomiólisis/patologíaRESUMEN
Alport syndrome (AS) is a rare genetic disorder categorized by the progressive loss of kidney function, sensorineural hearing loss and eye abnormalities. It occurs due to mutations in three genes that encode for the alpha chains of type IV collagen. Globally, the disease is classified based on the pattern of inheritance into X-linked AS (XLAS), which is caused by pathogenic variants in COL4A5, representing 80% of AS. Autosomal recessive AS (ARAS), caused by mutations in either COL4A3 or COL4A4, represents 15% of AS. Autosomal dominant AS (ADAS) is rare and has been recorded in 5% of all cases due to mutations in COL4A3 or COL4A4. This review provides updated knowledge about AS including its clinical and genetic characteristics in addition to available therapies that only slow the progression of the disease. It also focuses on reported cases in Saudi Arabia and their prevalence. Moreover, we shed light on advances in genetic technologies like gene editing using CRISPR/Cas9 technology, the need for an early diagnosis of AS and managing the progression of the disease. Eventually, we provide a few recommendations for disease management, particularly in regions like Saudi Arabia where consanguineous marriages increase the risk.
RESUMEN
BACKGROUND: The findings of earlier investigations of antiapoptotic gene genotypes and allele variants on lymphoma risk are ambiguous. This study aimed to examine the relationship between the mutation in the antiapoptotic genes and lymphoma risk among Saudi patients. METHODS: This case-control study included 205 patients, 100 of whom had lymphoma (cases) and 105 who were healthy volunteers (controls). We used tetra amplification refractory mutation polymerase chain reaction (PCR) to identify antiapoptotic genes such as B-cell lymphoma-2 (BCL2-938 C > A), MCL1-rs9803935 T > G, and survivin (BIRC5-rs17882312 G > C and BIRC5-rs9904341 G > C). Allelic-specific PCR was used to identify alleles such as BIRC5-C, MCL1-G, and BIRC5-G. RESULTS: The dominant inheritance model among cases showed that mutations in all four antiapoptotic genes were more likely to be associated with the risk of lymphoma by the odds of 2.0-, 1.98-, 3.90-, and 3.29-fold, respectively, compared to controls. Apart from the BCL-2-A allele, all three specified alleles were more likely to be associated with lymphoma by the odds of 2.04-, 1.65-, and 2.11-fold, respectively. CONCLUSION: Unlike healthy individuals, lymphoma patients are more likely to have antiapoptotic gene genotypes and allele variants, apart from BCL-2-A alterations. In the future, these findings could be used to classify and identify patients at risk of lymphoma.
RESUMEN
Genome-wide association studies have reported link between SNPs and risk of breast cancer. This study investigated the association of the selected gene variants by predicting them as possible target genes. Molecular technique advances with the availability of whole-exome sequencing (WES), now offer opportunities for simultaneous investigations of many genes. The experimental protocol for PI3K, AKT-1, KLF-14, MDM4, miRNAs 27a, and miR-196a genotyping was done by ARMS-PCR and sanger sequencing. The novel and known gene variants were studied by Whole-exome sequencing using Illumina NovaSeq 6000 platform. This case control study reports significant association between BC patients, healthy controls with the polymorphic variants of PI3K C > T, AKT-1 G > A KLF 14 C > T, MDM4 A > G, miR-27a A > G, miR-196a-2 C > T genes (p < 0.05). MDM4 A > G genotypes were strongly associated with BC predisposition with OR 2.08 & 2.15, p < 0.05) in codominant and dominant models respectively. MDM4 A allele show the same effective (OR1.76, p < 0.05) whereas it remains protective in recessive model for BC risk. AKT1G > A genotypes were strongly associated with the BC susceptibility in all genetic models whereas PI3K C > T genotypes were associated with breast cancer predisposition in recessive model OR 6.96. Polymorphic variants of KLF-14 A > G, MDM4G > A, MiR-27aA >G, miR-196a-C > T were strongly associated with stage, tamoxifen treatment. Risk variants have been reported by whole exome sequencing in our BC patients. It was concluded that a strong association between the PI3K-AKT signaling pathway gene variants with the breast cancer susceptibility and progression. Similarly, KLF 14-AA, MDM4-GA, miR27a-GG and miR-196a-CT gene variants were associated with the higher risk probability of BC and were strongly correlated with staging of the BC patients. This study also reported Low, novel, and intermediate-genetic-risk variants of PI3K, AKT-1, MDM4G & KLF-14 by utilizing whole-exome sequencing. These variants should be further investigated in larger cohorts' studies.
RESUMEN
The coronavirus disease (COVID-19) pandemic has rapidly extended globally and killed approximately 5.83 million people all over the world. But, to date, no effective therapeutic against the disease has been developed. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enters the host cell through the spike glycoprotein (S protein) of the virus. Subsequently, RNA-dependent RNA polymerase (RdRp) and main protease (Mpro) of the virus mediate viral transcription and replication. Mechanistically inhibition of these proteins can hinder the transcription as well as replication of the virus. Recently oxysterols and its derivative, such as 25 (S)-hydroxycholesterol (25-HC) has shown antiviral activity against SARS-CoV-2. But the exact mechanisms and their impact on RdRp and Mpro have not been explored yet. Therefore, the study aimed to identify the inhibitory activity of 25-HC against the viral enzymes RdRp and Mpro simultaneously. Initially, a molecular docking simulation was carried out to evaluate the binding activity of the compound against the two proteins. The pharmacokinetics (PK) and toxicity parameters were analyzed to observe the 'drug-likeness' properties of the compound. Additionally, molecular dynamics (MD) simulation was performed to confirm the binding stability of the compound to the targeted protein. Furthermore, molecular mechanics generalized Born surface area (MM-GBSA) was used to predict the binding free energies of the compound to the targeted protein. Molecular docking simulation identified low glide energy -51.0 kcal/mol and -35.0 kcal/mol score against the RdRp and Mpro, respectively, where MD simulation found good binding stability of the compound to the targeted proteins. In addition, the MM/GBSA approach identified a good value of binding free energies (ΔG bind) of the compound to the targeted proteins. Therefore, the study concludes that the compound 25-HC could be developed as a treatment and/or prevention option for SARS-CoV-2 disease-related complications. Although, experimental validation is suggested for further evaluation of the work.Communicated by Ramaswamy H. Sarma.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Hidroxicolesteroles/farmacología , Simulación del Acoplamiento Molecular , Inhibidores Enzimáticos , Antivirales/farmacología , Simulación de Dinámica Molecular , Inhibidores de ProteasasRESUMEN
5-Fluorouracil (5-FU) is a chemotherapy used to treat many types of cancer. Cardiotoxicity is one of the common drawbacks of 5-FU therapy. Quercetin (Qu) is a bioflavonoid with striking biological activities. This research aimed to assess the ameliorative effect of Qu against 5-FU-mediated cardiotoxicity. Thirty-five rats were allocated into five groups: control group (normal saline), 5-FU group (30 mg/kg, intraperitoneally), Qu group (50 mg/kg, oral), 25 mg/kg Qu+5-FU group, and 50 mg/kg Qu+5-FU. The experimental animals were received the above-mentioned drugs for 21 days. Results showed that 5-FU significantly elevated creatine kinase, lactate dehydrogenase, serum cholesterol and triglyceride, and upregulated troponin and renin mRNA expression. Additionally, cardiac oxidant/antioxidant imbalance was evident in elevated oxidants (malondialdehyde and nitric oxide) and depleted antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). 5-FU also downregulated the gene expression of nuclear factor erythroid 2-related factor 2. Furthermore, 5-FU significantly increased cardiac pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and upregulated gene expression of nuclear factor kappa-B. 5-FU significantly enhanced cardiac apoptosis through upregulating caspase-3 expression and downregulating B-cell lymphoma 2. Immunohistochemical and histopathological examinations verified the above-mentioned findings. However, all these changes were significantly ameliorated in Qu pre-administered rats. Conclusively, Qu counteracted 5-FU-mediated cardiotoxicity through potent antioxidant, anti-inflammatory, and anti-apoptotic effects.
Asunto(s)
Antioxidantes , Quercetina , Ratas , Animales , Antioxidantes/metabolismo , Quercetina/farmacología , FN-kappa B/metabolismo , Cardiotoxicidad/prevención & control , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/metabolismo , Estrés Oxidativo , Factor 2 Relacionado con NF-E2/metabolismo , Caspasa 3/metabolismo , Doxorrubicina , ApoptosisRESUMEN
Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population. Materials and Methods: In this study, 11 patients with chronic kidney disease were enrolled. The diagnosis of ADPKD was based on history and diagnostic images: CT images include enlargement of renal outlines, renal echogenicity, and presence of multiple renal cysts with dilated collecting ducts, loss of corticomedullary differentiation, and changes in GFR and serum creatinine levels. Next-generation whole-exome sequencing was conducted using the Ion Torrent PGM platform. Results: Of the 11 Saudi patients diagnosed with chronic kidney disease (CKD) and ADPKD, the most common heterozygote nonsynonymous variant in the PKD1 gene was exon15: (c.4264G > A). Two missense mutations were identified with a PKD1 (c.1758A > C and c.9774T > G), and one patient had a PKD2 mutation (c.1445T > G). Three detected variants were novel, identified at PKD1 (c.1758A > C), PKD2L2 (c.1364A > T), and TSC2 (deletion of a'a at the 3'UTR, R1680C) genes. Other variants in PKD1L1 (c.3813_381 4delinsTG) and PKD1L2 (c.404C > T) were also detected. The median age of end-stage renal disease for ADPK patients in Saudi Arabia was 30 years. Conclusion: This study reported a common variant in the PKD1 gene in Saudi patients with typical ADPKD. We also reported (to our knowledge) for the first time two novel missense variants in PKD1 and PKD2L2 genes and one indel mutation at the 3'UTR of the TSC2 gene. This study establishes that the reported mutations in the affected genes resulted in ADPKD development in the Saudi population by a median age of 30. Nevertheless, future protein−protein interaction studies to investigate the influence of these mutations on PKD1 and PKD2 functions are required. Furthermore, large-scale population-based studies to verify these findings are recommended.
Asunto(s)
Fallo Renal Crónico , Riñón Poliquístico Autosómico Dominante , Insuficiencia Renal Crónica , Adulto , Humanos , Regiones no Traducidas 3' , Proteínas de la Membrana/genética , Mutación/genética , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/diagnóstico , Arabia Saudita , Canales Catiónicos TRPP/genética , Secuenciación del ExomaRESUMEN
The unprecedented health catastrophe derived from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 infection) met with a phenomenal scientific response across the globe. Worldwide, the scientific community was focused on finding a cure for the deadly disease. A wide range of research studies has consistently revealed the link between SARS-CoV-2 infection severity and abnormal gut microbiomes, suggesting its potential in developing novel therapeutic approaches. Probiotics have been extensively studied to promote health in human hosts and reestablish a balance in the dysbiotic gut microbiome; however, there is strong skepticism about their safety and efficacy. Consequently, the metabolic signatures of probiotics, often referred to as "postbiotics", could prove of paramount importance for adjuvant cures in patients with SARS-CoV-2. Postbiotics exhibit safety, enhanced shelf-life, and stability and, therefore, could be implemented in SARS-CoV-2 prophylactic strategies with no undue adverse side effects. The current study is a preliminary investigation of the antiviral properties of postbiotic metabolites derived from Leuconostoc mesenteroides GBUT-21. The study focuses on the potential biological role in inactivating SARS-CoV-2 and reducing related inflammatory pathways.
RESUMEN
Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma. Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4. Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events. Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.
RESUMEN
Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B-cells. In this study, bioinformatics analyses were conducted to identify possible pathogenic roles of CK2α, which is a protein encoded by CSNK2A1, in the progression and aggressiveness of CLL. Furthermore, various computational tools were used to search for a competent inhibitor of CK2α from fungal metabolites that could be proposed for CLL therapy. In CLL patients, high-expression of CSNK2A1 was associated with early need for therapy (n = 130, p < 0.0001) and short overall survival (OS; n = 107, p = 0.005). Consistently, bioinformatics analyses showed CSNK2A1 to associate with/play roles in CLL proliferation and survival-dependent pathways. Furthermore, PPI network analysis identified interaction partners of CK2α (PPI enrichment p value = 1 × 10-16) that associated with early need for therapy (n = 130, p < 0.003) and have been known to heavily impact on the progression of CLL. These findings constructed a rational for targeting CK2α for CLL therapy. Consequently, computational analyses reported 35 fungal metabolites out of 5820 (filtered from 19,967 metabolites) to have lower binding energy (ΔG: - 10.9 to - 11.7 kcal/mol) and better binding affinity (Kd: 9.77 × 107 M-1 to 3.77 × 108 M-1) compared with the native ligand (ΔG: - 10.8, Kd: 8.3 × 107 M--1). Furthermore, molecular dynamics simulation study established that Butyl Xanalterate-CK2α complex continuously remained stable throughout the simulation time (100 ns). Moreover, Butyl Xanalterate interacted with most of the catalytic residues, where complex was stabilized by more than 65% hydrogen bond interactions, and a significant hydrophobic interaction with residue Phe113. Here, high-expression of CSNK2A1 was implicated in the progression and poor prognosis of CLL, making it a potential therapeutic target in the disease. Butyl Xanalterate showed stable and strong interactions with CK2α, thus we propose it as a competitive inhibitor of CK2α for CLL therapy.
Asunto(s)
Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/metabolismo , Ligandos , Linfocitos B/metabolismo , Biología Computacional , PronósticoRESUMEN
Cancer is a major health concern and accounts for one of the main causes of death worldwide. Innovative strategies are needed to aid in the diagnosis and treatment of different types of cancers. Recently, there has been an evolving interest in utilizing nanobodies of camel origin as therapeutic tools against cancer. Nanotechnology uses nanobodies an emerging attractive field that provides promises to researchers in advancing different scientific sectors including medicine and oncology. Nanobodies are characteristically small-sized biologics featured with the ability for deep tissue penetration and dissemination and harbour high stability at high pH and temperatures. The current review highlights the potential use of nanobodies that are naturally secreted in camels' biological fluids, both milk and urine, in the development of nanotechnology-based therapy for treating different typesQuery of cancers and other diseases. Moreover, the role of nano proteomics in the invention of novel therapeutic agents specifically used for cancer intervention is also illustrated.
RESUMEN
Makkah in Saudi Arabia hosts the largest annual religious event in the world. Despite the many strict rules enacted, including Hajj cancellation, city lockdowns, and social distancing, the region has the second highest number of new COVID-19 cases in Saudi Arabia. Public health interventions that identify, isolate, and manage new cases could slow the infection rate. While RT-PCR is the current gold standard in SARS-CoV-2 identification, it yields false positive and negative results, which mandates the use of complementary serological tests. Here, we report the utility of serological assays during the acute phase of individuals with moderate and severe clinical manifestations of SARS-CoV-2 (COVID19). Fifty participants with positive RT-PCR results for SARS-CoV-2 were enrolled in this study. Following RT-PCR diagnosis, serum samples from the same participants were analyzed using in-house ELISA (IgM, IgA, and IgG) and microneutralization test (MNT) for the presence of antibodies. Of the 50 individuals analyzed, 43 (86%) showed a neutralizing antibody titer of ≥20. Univariate analysis with neutralizing antibodies as a dependent variable and the degree of disease severity and underlying medical conditions as fixed factors revealed that patients with no previous history of non-communicable diseases and moderate clinical manifestation had the strongest neutralizing antibody response "Mean: 561.11". Participants with severe symptoms and other underlying disorders, including deceased individuals, demonstrated the lowest neutralizing antibody response. Anti-spike protein antibody responses, as measured by ELISA, showed a statistically significant correlation with neutralizing antibodies. This reinforces the speculation that serological assays complement molecular testing for diagnostics; however, patients' previous medical history (anamnesis) should be considered in interpreting serological results.
RESUMEN
Gene therapy delivers a promising hope to cure many diseases and defects. The discovery of gene-editing technology fueled the world with valuable tools that have been employed in various domains of science, medicine, and biotechnology. Multiple means of gene editing have been established, including CRISPR/Cas, ZFNs, and TALENs. These strategies are believed to help understand the biological mechanisms of disease progression. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been designated the causative virus for coronavirus disease 2019 (COVID-19) that emerged at the end of 2019. This viral infection is a highly pathogenic and transmissible disease that caused a public health pandemic. As gene editing tools have shown great success in multiple scientific and medical areas, they could eventually contribute to discovering novel therapeutic and diagnostic strategies to battle the COVID-19 pandemic disease. This review aims to briefly highlight the history and some of the recent advancements of gene editing technologies. After that, we will describe various biological features of the CRISPR-Cas9 system and its diverse implications in treating different infectious diseases, both viral and non-viral. Finally, we will present current and future advancements in combating COVID-19 with a potential contribution of the CRISPR system as an antiviral modality in this battle.
Asunto(s)
COVID-19 , Virosis , COVID-19/terapia , Edición Génica , Humanos , Pandemias , SARS-CoV-2/genéticaRESUMEN
The full-length BRCA1-associated RING domain 1 (BARD1) gene encodes a 777-aa protein. BARD1 displays a dual role in cancer development and progression as it acts as a tumor suppressor and an oncogene. Structurally, BARD1 has homologous domains to BRCA1 that aid their heterodimer interaction to inhibit the progression of different cancers such as breast and ovarian cancers following the BRCA1-dependant pathway. In addition, BARD1 was shown to be involved in other pathways that are involved in tumor suppression (BRCA1-independent pathway) such as the TP53-dependent apoptotic signaling pathway. However, there are abundant BARD1 isoforms exist that are different from the full-length BARD1 due to nonsense and frameshift mutations, or deletions were found to be associated with susceptibility to various cancers including neuroblastoma, lung, breast, and cervical cancers. This article reviews the spectrum of BARD1 full-length genes and its different isoforms and their anticipated associated risk. Additionally, the study also highlights the role of BARD1 as an oncogene in breast cancer patients and its potential uses as a prognostic/diagnostic biomarker and as a therapeutic target for cancer susceptibility testing and treatment.
Asunto(s)
Neoplasias , Proteínas Supresoras de Tumor , Ubiquitina-Proteína Ligasas , Femenino , Genes Supresores de Tumor , Humanos , Neoplasias/genética , Isoformas de Proteínas/genética , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
The success of the Saudi Human Genome Program (SHGP), one of the top ten genomic programs worldwide, is highly dependent on the Saudi population embracing the concept of participating in genetic testing. However, genetic data sharing and artificial intelligence (AI) in genomics are critical public issues in medical care and scientific research. The present study was aimed to examine the awareness, knowledge, and attitude of the Saudi society towards the SHGP, the sharing and privacy of genetic data resulting from the SHGP, and the role of AI in genetic data analysis and regulations. Results of a questionnaire survey with 804 respondents revealed moderate awareness and attitude towards the SHGP and minimal knowledge regarding its benefits and applications. Respondents demonstrated a low level of knowledge regarding the privacy of genetic data. A generally positive attitude was found towards the outcomes of the SHGP and genetic data sharing for medical and scientific research. The highest level of knowledge was detected regarding AI use in genetic data analysis and privacy regulation. We recommend that the SHGP's regulators launch awareness campaigns and educational programs to increase and improve public awareness and knowledge regarding the SHGP's benefits and applications. Furthermore, we propose a strategy for genetic data sharing which will facilitate genetic data sharing between institutions and advance Personalized Medicine in genetic diseases' diagnosis and treatment.
Asunto(s)
Inteligencia Artificial , Pruebas Genéticas/ética , Conocimientos, Actitudes y Práctica en Salud , Difusión de la Información/ética , Medicina de Precisión/psicología , Adolescente , Adulto , Estudios Transversales , Femenino , Genoma Humano , Humanos , Masculino , Persona de Mediana Edad , Arabia Saudita , Encuestas y CuestionariosRESUMEN
BACKGROUND: Despite the advancement in the fields of medical science and molecular biology, cancer is still the leading cause of death worldwide. Chemotherapy is a choice for treatment; however, the acquisition of chemoresistance is a major impediment for cancer management. Many mechanisms have been postulated regarding the acquisition of chemo-resistance in breast cancer and the impact on cellular signalling and the induction of apoptosis in tumour cells. The mechanism of the apoptotic mutation ofp53 and bcl-2 proteins is commonly associated with increased resistance to apoptosis and, therein, to chemotherapy. OBJECTIVES: The current study was aimed to investigate A172 and MDA-MB-231 cancer cells'sensitivity against chemotherapeutic drugs, including cisplatin, doxorubicin, and paclitaxel with different doses. Moreover, it estimates resistance of cancer cells by evaluating Nitric Oxide Synthase (NOS) expression and evaluate its correlation with the expression profile proteins of the apoptosis regulating Bcl-2 family. METHODS: Dose-dependent sensitivity to cisplatin, doxorubicin or paclitaxel was evaluated on spheroid cultured A172 and MDA-MB-231 cells lines, was measured by time-lapse microscopy over a 72h period. Expressions of two Nitric Oxide (NO) synthases isoforms (iNOS, eNOS), anti-apoptotic (Bcl-2, phospho-Bcl-2, Mcl-1, and Bcl-xL) and proapoptotic (BID, Bim, Bok, Bad, Puma, and Bax) were evaluated by Western blot. The effect of NO modulation on antiand pro-apoptotic molecule expression was also studied using Western blot. RESULTS: A172 cells show more resistance to chemotherapy drugs than MDA-MB-231 cancer cells, therefore, they need higher doses for apoptosis. Resistance of gliomas might be returned to higher significant expression of endothelial eNOS expression. It was clear that there is not a significant effect of NO modulation on the expression of pro- andantiapoptotic proteins on both cell lines. CONCLUSION: The present work provides a putative mechanism for the acquisition of drug resistance in breast cancer and glioma, which might be significant for clinical outcomes.
Asunto(s)
Neoplasias de la Mama , Cisplatino , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Humanos , Óxido Nítrico Sintasa/farmacología , Óxido Nítrico Sintasa/uso terapéutico , Paclitaxel/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
BACKGROUND: Colorectal cancer (CRC) is a major health concern worldwide. A series of sequential accumulation of genetic and epigenetic changes are responsible for the initiation and progression of diseases via the normal > adenoma > carcinoma sequence. Genetic variants in crucial cancer-causing genes are known to mediate the risk of cancer. OBJECTIVE: In this case-control study, we examined single nucleotide polymorphism (SNP) in HER1 (rs763317 and rs3752651) and HER2 (rs1136201 and rs1058808) genes to assess their role in the susceptibility of CRC in a Saudi population. METHODS: TaqMan allelic discrimination assay was utilized to identify the genotypes in 163 normal and 143 CRC patients. RESULTS: In the overall analysis, the rs3752651 and rs1136201 were significantly associated with the risk of CRC. Although none of the examined SNPs had any impact on the age at which CRC was diagnosed, interestingly, three SNPs showed a significant association based on gender. The rs3752651 conferred significant protection only in men, whereas rs1136201 diminished the risk and rs1058808 considerably increased the susceptibility of CRC only in women. CONCLUSIONS: Our result suggests that these SNPs in HER1 and HER2 after validation in larger cohorts of different ethnicities may be utilized as genetic screening markers for predicting colorectal cancer predisposition.