Background Ewing's sarcoma (ES) of the hip and trochanteric region is a rare malignancy. The tumor has a poor prognosis due to the problems in early diagnosis and medical intervention. Case presentation This paper reports a rare case of hip ES presented in a 34y/o female. The clinical, radiological, and histopathological features were all in favor of ES. Following treatment by neoadjuvant/adjuvant chemotherapy, and irradiation the patient is now with complete resolution of the tumor. Conclusion The patient remained free of disease through 4 years of follow-up until now after diagnosis.
background: Berberine is a plant alkaloid present in many plants. It has diverse curative effects including anti-inflammatory and antioxidant effects. The current study aimed to evaluate the protective activity of berberine and investigate its probable mechanisms against sodium nitrite toxicity in liver. method: Forty male rats were divided into five groups. Group one as the control group received normal saline, group two received berberine (100 mg kg-1) and group three received sodium nitrite (80 mg kg-1). Groups four and five received berberine in doses of 50 and 100 mg/Kg, respectively and sodium nitrite (80 mg kg-1) was given orally. All the doses were orally administrated for two months. Then At the end of 60th day, the animals were sacrificed, and liver homogenate, were prepared. For evaluating oxidative injury, the levels of albumin (ALB) and aspartate transaminase (AST) in serum and oxidative stress parameters in liver were analyzed. result: Treatment of rats with sodium nitrite, considerably increased the levels of serum AST, and liver superoxide anion as well as significantly reduced the levels of serum ALB, superoxide dismutase (SOD), total antioxidant capacity (TAC), and catalase (CAT) activity in liver tissue. Berberine treatment could ameliorate all these parameters dose dependently. Berberine at dose of 100 mg/kg had the best impact and reached the values of oxidative stress parameters to the normal level. conclusion: Our results clearly demonstrated that berberine in a dose dependent manner offers protection against sodium nitrite-induced oxidative injury, which possibly reflects the antioxidant abilities of this alkaloid.
Background: The coronavirus disease 2019 (COVID-19) pandemic is a contagious disease originating from severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Previous experimental studies indicate that viral miRNAs (vMirs) have essential functions in pathogen-host interaction, immune escape, host cell death, and tumorigenesis during viral infection. MiRNAs are small, single-stranded RNAs that exist in viruses as well as in animals. Thus, these molecules can play a pivotal role in viral disease pathogenesis. Objective: Since no approved drugs or vaccines currently exist for SARS-CoV2 and its pathogenic mechanism is unknown, we explored and proposed viral microRNAs (vmiRNAs) platforms as potential antiviral therapeutic agents against its SARS-CoV2. Therefore, the development of antiviral drugs to target vmiRNAs may result in down-regulation of viral virulence genes expression and suppression of viral proliferation. Methods: In this study, to attain insight into the potential role of SARS-CoV2 derived miRNAs in the viral infection background, we used a set of computational methods to scan the SARS-CoV2 genome that finally led to computationally predicted 13 potential candidate viral microRNAs. Furthermore, we expected the potential genes in a human host that were the target of these candidate vmiRNAs by applying mirPath software. Results: Our study proposed a theory indicating that these predicted viral miRNAs might have a plausible role in altering human target gene expression, mainly contributing to the viral infectious state, inflammation, and immune system escape. This vmiRNAs maight have therapeutic trends as antiviral agents against Covid-19 infection. Conclusion: These findings offer a reference idea for a supplementary study on miRNA identification as a drug target and the necessity to increase understanding of SARS-CoV2 genome structure for better combat against the virus.
Background: MicroRNAs (miRNAs) have a pivotal role in Hepatitis B Virus (HBV) infection and its complications by targeting the cellular transcription factors required for HBV genes expression or by directly binding to HBV transcripts. Single Nucleotide Polymorphisms (SNPs) in miRNA genes affect their expression as well as the regulation of target genes, clinical course, diagnosis, and therapeutic interventions of HBV infection. Methods: Computational assessment and cataloging of miRNA gene polymorphisms targeting mRNA transcripts straightly or indirectly through the regulation of hepatitis B infection by annotating the functional impact of SNPs on mRNA-miRNA and miRNA-RBS (miRNA binding sites) interaction were screened by applying various universally available datasets such as the miRNA SNP3.0 software. Results: A total of 2987 SNPs were detected in 139 miRNAs affecting hepatitis B infection. Among them, 313 SNPs were predicted to have a significant role during the progression of hepatitis B infection. The computational analysis also revealed that 45 out of the 313 SNPs were located in the seed region and were more important than others. Has-miR-139-3p had the largest number of SNPs in the seed region (n=6). On the other hand, proteoglycans in cancer, adherens junction, lysine degradation, NF-kappa B signaling cascade, ECM-receptor binding, viral carcinogenesis, fatty acid metabolism, TGF-beta signaling pathway, p53 signaling pathway, immune evasion related pathways, and fatty acid biosynthesis were the most important pathways affected by these 139 miRNAs. Conclusion: The results revealed 45 SNPs in the seed region of 25 miRNAs as the catalog in miRNA genes that regulated the hepatitis B infection. The results also showed the most important pathways regulated by these miRNAs that can be targeted for therapeutic purposes.
Objective: Berberine, a plant derived alkaloid, present in Berberis species and is well known as one of the most important antioxidants. The current research aimed to study the heamatoprotective characteristics of berberine and clarify its plausible mechanisms against sodium nitrite. Methods: Forty numbers of male Sprague Dawley rats were categorized into five equal groups, including group 1: control (normal saline); group 2: berberine (100 mg/kg); group 3: sodium nitrite (80 mg/kg); group 4: sodium nitrite (80 mg/kg) plus berberine (50 mg/kg) and group 5: sodium nitrite (80 mg/kg) plus berberine (100 mg/kg) groups. All animals were orally administrated for two months once daily. At the end of the 60th day, blood samples were withdrawn by cardiac puncture and collected in test vials when the animals had been anesthetized with ketamine (70 mg/kg). Then, hemolysate was prepared and the oxidative stress biomarkers, lipid peroxidation, and antioxidant capacity of erythrocytes were evaluated. Results: Feeding of rats with sodium nitrite remarkably enhanced malondialdehyde (MDA) (p=0.001) levels and considerably reduced the levels of glutathione (GSH) (p=0.001), and also reduced the enzymatic activities of glutathione peroxidase (GPx) (p=0.02), superoxide dismutase (SOD) (p=0.001), glutathione reductase (GR) (p=0.02), and catalase (CAT) (p=0.01). However, the co-administration of these animals with 100 mg/kg of berberine remarkably reverted the values to reach nearly a normal level. While 50 mg/kg berberine failed to restore significantly all of these antioxidant biomarkers at a normal level. Conclusion: Our results clearly demonstrated that berberine in a dose-dependent manner led to protection against sodium nitrite-induced oxidative injury in rat erythrocytes, which possibly reflects the antioxidant ability of this alkaloid.
Background: The fast development of an effective vaccine is the major demand for protection against the SARS-COV-2 virus outbreak. With the vast volume of data and the requirement for automatic abstract property learning, machine learning (ML) as a branch of artificial intelligence (AI) has a significant contribution in areas of vaccine discovery. The rise of ML has greatly accelerated the often lengthy vaccine approval process. ML models for COVID-19 vaccine development focus on the prediction of potential epitopes by using a variety of techniques, such as artificial neural network, gradient boosting decision tree and deep neural network. In this regard, immuno-informatics tools are time-saving and cost-effective methods to hasten the design and establishment of a proficient multi-peptide candidate vaccine. The utilization of multi-epitope-based vaccines has been demonstrated to be a promising immunization approach against viruses due to the induction of long-term protective immunity. Methods: In the present study, a comprehensive computational and machine learning based approach was conducted to design a multi-epitope-based potential candidate vaccine composed of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes of conserved regions of Spike and Nucleocapsid proteins. The potential viral peptides as the candidate vaccine were screened regarding convenient features like hydrophilicity, flexibility, antigenicity, and charging properties. In the next step, the vaccine efficacy needs to be improved by an immune adjuvant. For this purpose, the C-terminal domain of the heat shock protein gp96 (CT-GP96) was applied as a potent adjuvant for enhancing immunity. The five assembled constructs with different peptide orders were generated and fused with the assistance of suitable linkers. All five assembled candidate vaccine constructs were modeled and their 3D structures were assessed in terms of strong immune responses stimulation and their structural stability and immune processing for response induction. Finally, the best refined model was docked to toll-like receptor 4 (TLR4). Furthermore, Molecular Dynamics (MD) simulation of the vaccine receptor complex was done to assess the stability and related physical movements of the vaccine-TLR4 docking complex. The final candidate vaccine was computationally cloned in E. coli expression host to guarantee its high level production. Results: Following a comprehensive immune-informatics and machine learning based approach, the best conserved CTL and HTL immune stimulant epitopes were selected and assembled in different orders to build five different constructs. The final validated candidate vaccine construct was selected according to its efficacy, stability, and exposure ability, molecular docking analysis with TLR4. The molecular simulations by iMODS software also confirmed the stability of the binding interface. Additionally, the computational cloning of the final assembled candidate vaccine with pET28a plasmid showed the possibility of high level production of the vaccine construct post transformation in an E. coli host. Conclusion: The computational analysis indicated that this construct can be proposed as a potent prophylactic and therapeutic candidate multi-epitope vaccine against SARS‐COV‐2 once its effectiveness is verified by experimental and animal studies.
Nigella sativa L. (Ranunculaceae) is one of the most widely used traditional therapeutic plants. It possesses important classes of bioactive compounds among which thymoquinone as the major bioactive component of the essential oil has attracted noteworthy attention due to its active role in treating a various range of disorders. N. sativa can induce a wide range of pharmacological functions including anti-oxidative stress responses, antidiabetic, anticancer, cell apoptosis and increase membrane permeability, immunomodulatory, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilatory, hepato-protective, renal protective, gastro-protective, and antioxidant properties. The seeds of N. sativa , commonly known as black seed or black cumin, show many potential pharmacological roles and are utilized in folk (herbal) medicine all over the world for the treatment and prevention of a various range of diseases and conditions including asthma, cancers, inflammatory situations, type 2 diabetes mellitus disorders, bacterial and viral infections, and dyslipidemia. This review outlines the main pharmacological properties of N. sativa and its components due to their potential wide applications for a large variety of human diseases. The seeds constitute both fixed and essential oils, proteins, alkaloids and saponin. Much of the biological function of the seeds has been demonstrated to be due to thymoquinone. Beneficial influences of the seeds application and thymoquinone might be contributed to their cytoprotective and antioxidant functions, and to their effect on immune response and some inflammatory mediators.
Background: The fast development of an effective vaccine is the major demand for protection against the SARS-COV-2 virus outbreak. Immuno-informatics tools are time-saving and cost-effective methods to hasten the design and establishment of a proficient multi-peptide candidate vaccine. The utilization of multi-epitope-based vaccines has demonstrated to be a promising immunization approach against viruses due to the induction of long-term protective immunity. Method: In the present study, a complete computational approach was conducted to design a multi-epitope-based vaccine composed of cytotoxic T lymphocyte and helper T lymphocyte epitopes of Spike and Nucleocapsid proteins conserved regions. The potential viral peptides as the candidate vaccine were screened regarding convenient features like hydrophilicity, flexibility, antigenicity, and charged properties. In the next step, the vaccine efficacy needed to be improved by an immune adjuvant. For this purpose, the C-terminal domain of heat shock protein gp96 (CT-GP96) was applied as a potent adjuvant for enhancing immunity. The final assembled construct was fused with the assistance of suitable linkers and cloned in a pET28a expression vector for overproduction of the vaccine in a bacterial host. Result: Following validation of the final construct in terms of its efficacy, stability, and exposure ability, molecular docking analysis was carried out to reveal its interaction with toll-like receptor 4, which is required to trigger the immune response. The molecular simulations by iMODS software confirmed the stability of the binding interface. Additionally, the computational cloning of the assembled vaccine in pET28a plasmid showed the possibility of producing a vaccine construct post-transformation in an E. coli host. Conclusion: The computational analysis indicated that this construct could be a potent prophylactic and therapeutic multi-epitope vaccine candidate against SARS‐COV‐2 once its effectiveness is verified by experimental and animal studies.
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