A computational approach to design a multiepitope vaccine against H5N1 virus.

Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human ß-defensin-3 (HßD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.

Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.

Chemotherapy and radiotherapy are widely used in clinical practice across the globe as cancer treatments. Intrinsic or acquired chemoresistance poses a significant problem for medical practitioners and researchers, causing tumor recurrence and metastasis. The most dangerous kind of malignant brain tumor is called glioblastoma multiforme (GBM) that often recurs following surgery. The most often used medication for treating GBM is temozolomide chemotherapy; however, most patients eventually become resistant. Researchers are studying preclinical models that accurately reflect human disease and can be used to speed up drug development to overcome chemoresistance in GBM. Non-coding RNAs (ncRNAs) have been shown to be substantial in regulating tumor development and facilitating treatment resistance in several cancers, such as GBM. In this work, we mentioned the mechanisms of how different ncRNAs (microRNAs, long non-coding RNAs, circular RNAs) can regulate temozolomide chemosensitivity in GBM. We also address the role of these ncRNAs encapsulated inside secreted exosomes.

Imaging Techniques and Biochemical Biomarkers: New Insights into Diagnosis of Pancreatic Cancer.

Pancreatic cancer (PaC) incidence is increasing, but our current screening and diagnostic strategies are not very effective. However, screening could be helpful in the case of PaC, as recent evidence shows that the disease progresses gradually. Unfortunately, there is no ideal screening method or program for detecting PaC in its early stages. Conventional imaging techniques, such as abdominal ultrasound, CT, MRI, and EUS, have not been successful in detecting early-stage PaC. On the other hand, biomarkers may be a more effective screening tool for PaC and have greater potential for further evaluation compared to imaging. Recent studies on biomarkers and artificial intelligence (AI)-enhanced imaging have shown promising results in the early diagnosis of PaC. In addition to proteins, non-coding RNAs are also being studied as potential biomarkers for PaC. This review consolidates the current literature on PaC screening modalities to provide an organized framework for future studies. While conventional imaging techniques have not been effective in detecting early-stage PaC, biomarkers and AI-enhanced imaging are promising avenues of research. Further studies on the use of biomarkers, particularly non-coding RNAs, in combination with imaging modalities may improve the accuracy of PaC screening and lead to earlier detection of this deadly disease.

Potential of Natural Products in the Treatment of Glioma: Focus on Molecular Mechanisms.

Despite the waning of traditional treatments for glioma due to possible long-term issues, the healing possibilities of substances derived from nature have been reignited in the scientific community. These natural substances, commonly found in fruits and vegetables, are considered potential alternatives to pharmaceuticals, as they have been shown in prior research to impact pathways surrounding cancer progression, metastases, invasion, and resistance. This review will explore the supposed molecular mechanisms of different natural components, such as berberine, curcumin, coffee, resveratrol, epigallocatechin-3-gallate, quercetin, tanshinone, silymarin, coumarin, and lycopene, concerning glioma treatment. While the benefits of a balanced diet containing these compounds are widely recognized, there is considerable scope for investigating the efficacy of these natural products in treating glioma.