Multi-epitopevaccines, from design to expression; an in silico approach.

The development of vaccines against a wide range of infectious diseases and pathogens often relies on multi-epitope strategies that can effectively stimulate both humoral and cellular immunity. Immunoinformatics tools play a pivotal role in designing such vaccines, enhancing immune response potential, and minimizing the risk of failure. This review presents a comprehensive overview of practical tools for epitope prediction and the associated immune responses. These immunoinformatics tools facilitate the selection of epitopes based on parameters such as antigenicity, absence of toxic and allergenic sequences, secondary and tertiary structures, sequence conservation, and population coverage. The chosen epitopes can be tailored for B-cells or T-cells, both of which require further assessments covered in this study. We offer a range of suitable linkers that effectively separate cytotoxic T lymphocyte and helper T lymphocyte epitopes while preserving their functionality. Additionally, we identify various adjuvants for specific purposes. We delve into the evaluation of MHC-epitope interactions, MHC clusters, and the simulation of final constructs through molecular docking techniques. We provide diverse linkers and adjuvants optimized for epitope functions to bolster immune responses through epitope attachment. By leveraging these comprehensive tools, the development of multi-epitope vaccines holds the promise of robust immunity and a significant reduction in experimental costs.

Remdesivir: treatment of COVID-19 in special populations.

Remdesivir (RDV) is the mainstay antiviral therapy for moderate to severe COVID-19. Although remdesivir was the first drug approved for COVID-19, information about its efficacy and safety profile is limited in a significant segment of the population, such as people with underlying diseases, the elderly, children, and pregnant and lactating women. The efficacy and safety profile of RDV in disease progression, renal impairment, liver impairment, immunosuppression, geriatrics, pediatrics, pregnancy, and breastfeeding in COVID-19 patients was evaluated. The databases searched included Embase, Scopus, and PubMed. Only English language studies enrolling specific subpopulations with COVID-19 and treated with RDV were included. Thirty-nine clinical trials, cohorts, cross-sectional studies, and case series/reports were included. Most supported the benefits of RDV therapy for COVID-19 patients, such as lessening the duration of hospitalization, alleviating respiratory complications, and reducing mortality. Adverse effects of RDV, including liver and kidney impairment, were, for the most part, moderate to mild, supporting the safety profile of RDV therapy. RDV therapy was well tolerated, no new safety signals were detected, and liver function test abnormalities were the most common adverse events. Moreover, RDV, for the most part, was effective in managing the complications of COVID-19 and reducing mortality in these patients, except for patients with kidney impairment. Future studies, including RCTs, should include these subpopulations of patients to avoid delays associated with receiving proper medication through compassionate use programs.

Evaluation of silver sulfadiazine 1%-cerium nitrate 2.2% cream efficacy and safety in moderate to severe burn patients: a single-blind randomized clinical trial.

BACKGROUND: Burn injury is a major global health crisis. Topical antimicrobials such as silver sulfadiazine (SSD) are commonly used for superficial burn wounds. SSD has a broad-spectrum antimicrobial activity and also anti-inflammatory property, but also suffers from some limitations. Therefore, some studies suggest to add cerium nitrate (CN) to SSD, as an immunomodulatory and tanning agent with antitoxic properties, but its effect on patients' mortality, length of hospital stay, and bacterial colonization is contraversial. OBJECTIVES: In this research, we evaluated the efficacy and safety of SSD 1%+CN 2.2% cream in patients with moderate to severe burn. MATERIAL AND METHODS: Twenty-two patients who fulfilled the inclusion criteria randomly were assigned to the intervention (n=7) or control (n=15) group and received SSD 1%+CN 2.2% or SSD cream 1% respectively, once daily until the complete re-epithelization or prepration of the burned skin for grafting. Intesity of pain, re-epithelialization time, required interventions, laboratory and clinical findings and final outcome were recorded. RESULTS: There was no significant difference in re-epithelialization time between the treatment and control groups (P>0.05). The same findings were reported about the required interventions and laboratory and clinical parameters. However, the final outcome and the pain score on third day were significantly better in the treatment group (P=0.017). On the other hand, all patients in the treatment group needed graft surgery. CONCLUSION: Use of SSD 1%+CN 2.2% cream did not significantly improve re-epithelization time or infection occurrence and patients' pain, but also increased graft surgery rate in comparison with SDD 1% cream in moderate to severe burns.

Mas receptor: a potential strategy in the management of ischemic cardiovascular diseases.

MasR is a critical element in the RAS accessory pathway that protects the heart against myocardial infarction, ischemia-reperfusion injury, and pathological remodeling by counteracting the effects of AT1R. This receptor is mainly stimulated by Ang 1-7, which is a bioactive metabolite of the angiotensin produced by ACE2. MasR activation attenuates ischemia-related myocardial damage by facilitating vasorelaxation, improving cell metabolism, reducing inflammation and oxidative stress, inhibiting thrombosis, and stabilizing atherosclerotic plaque. It also prevents pathological cardiac remodeling by suppressing hypertrophy- and fibrosis-inducing signals. In addition, the potential of MasR in lowering blood pressure, improving blood glucose and lipid profiles, and weight loss has made it effective in modulating risk factors for coronary artery disease including hypertension, diabetes, dyslipidemia, and obesity. Considering these properties, the administration of MasR agonists offers a promising approach to the prevention and treatment of ischemic heart disease.Abbreviations: Acetylcholine (Ach); AMP-activated protein kinase (AMPK); Angiotensin (Ang); Angiotensin receptor (ATR); Angiotensin receptor blocker (ARB); Angiotensin-converting enzyme (ACE); Angiotensin-converting enzyme inhibitor (ACEI); Anti-PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16); bradykinin (BK); Calcineurin (CaN); cAMP-response element binding protein (CREB); Catalase (CAT); C-C Motif Chemokine Ligand 2 (CCL2); Chloride channel 3 (CIC3); c-Jun N-terminal kinases (JNK); Cluster of differentiation 36 (CD36); Cocaine- and amphetamine-regulated transcript (CART); Connective tissue growth factor (CTGF); Coronary artery disease (CAD); Creatine phosphokinase (CPK); C-X-C motif chemokine ligand 10 (CXCL10); Cystic fibrosis transmembrane conductance regulator (CFTR); Endothelial nitric oxide synthase (eNOS); Extracellular signal-regulated kinase 1/2 (ERK 1/2); Fatty acid transport protein (FATP); Fibroblast growth factor 21 (FGF21); Forkhead box protein O1 (FoxO1); Glucokinase (Gk); Glucose transporter (GLUT); Glycogen synthase kinase 3ß (GSK3ß); High density lipoprotein (HDL); High sensitive C-reactive protein (hs-CRP); Inositol trisphosphate (IP3); Interleukin (IL); Ischemic heart disease (IHD); Janus kinase (JAK); Kruppel-like factor 4 (KLF4); Lactate dehydrogenase (LDH); Left ventricular end-diastolic pressure (LVEDP); Left ventricular end-systolic pressure (LVESP); Lipoprotein lipase (LPL); L-NG-Nitro arginine methyl ester (L-NAME); Low density lipoprotein (LDL); Mammalian target of rapamycin (mTOR); Mas-related G protein-coupled receptors (Mrgpr); Matrix metalloproteinase (MMP); MAPK phosphatase-1 (MKP-1); Mitogen-activated protein kinase (MAPK); Monocyte chemoattractant protein-1 (MCP-1); NADPH oxidase (NOX); Neuropeptide FF (NPFF); Neutral endopeptidase (NEP); Nitric oxide (NO); Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB); Nuclear-factor of activated T-cells (NFAT); Pancreatic and duodenal homeobox 1 (Pdx1); Peroxisome proliferator- activated receptor γ (PPARγ); Phosphoinositide 3-kinases (PI3k); Phospholipase C (PLC); Prepro-orexin (PPO); Prolyl-endopeptidase (PEP); Prostacyclin (PGI2); Protein kinase B (Akt); Reactive oxygen species (ROS); Renin-angiotensin system (RAS); Rho-associated protein kinase (ROCK); Serum amyloid A (SAA); Signal transducer and activator of transcription (STAT); Sirtuin 1 (Sirt1); Slit guidance ligand 3 (Slit3); Smooth muscle 22α (SM22α); Sterol regulatory element-binding protein 1 (SREBP-1c); Stromal-derived factor-1a (SDF); Superoxide dismutase (SOD); Thiobarbituric acid reactive substances (TBARS); Tissue factor (TF); Toll-like receptor 4 (TLR4); Transforming growth factor ß1 (TGF-ß1); Tumor necrosis factor α (TNF-α); Uncoupling protein 1 (UCP1); Ventrolateral medulla (VLM).

LKB1: An emerging therapeutic target for cardiovascular diseases.

Cardiovascular diseases (CVDs) are currently the most common cause of morbidity and mortality worldwide. Experimental studies suggest that liver kinase B1 (LKB1) plays an important role in the heart. Several studies have shown that cardiomyocyte-specific LKB1 deletion leads to hypertrophic cardiomyopathy, left ventricular contractile dysfunction, and an increased risk of atrial fibrillation. In addition, the cardioprotective effects of several medicines and natural compounds, including metformin, empagliflozin, bexarotene, and resveratrol, have been reported to be associated with LKB1 activity. LKB1 limits the size of the damaged myocardial area by modifying cellular metabolism, enhancing the antioxidant system, suppressing hypertrophic signals, and inducing mild autophagy, which are all primarily mediated by the AMP-activated protein kinase (AMPK) energy sensor. LKB1 also improves myocardial efficiency by modulating the function of contractile proteins, regulating the expression of electrical channels, and increasing vascular dilatation. Considering these properties, stimulation of LKB1 signaling offers a promising approach in the prevention and treatment of heart diseases.

Resolvin D1, therapeutic target in acute respiratory distress syndrome.

Acute lung injury (ALI), or its more severe form, acute respiratory distress syndrome (ARDS), is a disease with high mortality and is a serious challenge facing the World Health Organization because there is no specific treatment. The excessive and prolonged immune response is the hallmark of this disorder, so modulating and regulating inflammation plays an important role in its prevention and treatment. Resolvin D1 (RvD1) as a specialized pro-resolving mediator has the potential to suppress the expression of inflammatory cytokines and to facilitate the production of antioxidant proteins by stimulating lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2). These changes limit the invasion of immune cells into the lung tissue, inhibit coagulation, and enhance cell protection against oxidative stress (OS). In particular, this biomolecule reduces the generation of reactive oxygen species (ROS) by blocking the activation of inflammatory transcription factors, especially nuclear factor-κB (NF-κB), and accelerating the synthesis of antioxidant compounds such as heme oxygenase 1 (HO-1) and superoxide dismutase (SOD). Therefore, the destruction and dysfunction of important cell components such as cytoplasmic membrane, mitochondria, Na+/k + adenosine triphosphatase (ATPase) and proteins involved in the phagocytic activity of scavenger macrophages are attenuated. Numerous studies on the effect of RvD1 over inflammation using animal models revealed that Rvs have both anti-inflammatory and pro-resolving capabilities and therefore, might have potential therapeutic value in treating ALI. Here, we review the current knowledge on the classification, biosynthesis, receptors, mechanisms of action, and role of Rvs in ALI/ARDS.

Nephroprotective activity of natural products against chemical toxicants: The role of Nrf2/ARE signaling pathway.

Nephropathy can occur following exposure of the kidneys to oxidative stress. Oxidative stress is the result of reactive oxygen species (ROS) formation due to intracellular catabolism or exogenous toxicant exposure. Many natural products (NPs) with antioxidant properties have been used to demonstrate that oxidative damage-induced nephrotoxicity can be ameliorated or at least reduced through stimulation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Nrf2 is a basic leucine zipper (bZip) transcription factor that regulates gene expression of the antioxidant response elements (ARE). Nrf2 is involved in the cellular antioxidant-detoxification machinery. Nrf2 activation is a major mechanism of nephroprotective activity for these NPs, which facilitates its entry into the nucleus, primarily by inhibiting Kelch like-ECH-associated protein 1 (Keap1). The purpose of this article was to review the peer-reviewed literature of NPs that have shown mitigating effects on renal disorder by stimulating Nrf2 and thereby suggesting potential new therapeutic or prophylactic strategies against kidney-damaging xenobiotics.

Holey-Cavity-Based Compressive Sensing for Ultrasound Imaging.

The use of solid cavities around electromagnetic sources has been recently reported as a mechanism to provide enhanced images at microwave frequencies. These cavities are used as measurement randomizers; and they compress the wave fields at the physical layer. As a result of this compression, the amount of information collected by the sensing array through the different excited modes inside the resonant cavity is increased when compared to that obtained by no-cavity approaches. In this work, a two-dimensional cavity, having multiple openings, is used to perform such a compression for ultrasound imaging. Moreover, compressive sensing techniques are used for sparse signal retrieval with a limited number of operating transceivers. As a proof-of-concept of this theoretical investigation, two point-like targets located in a uniform background medium are imaged in the presence and the absence of the cavity. In addition, an analysis of the sensing capacity and the shape of the point spread function is also carried out for the aforementioned cases. The cavity is designed to have the maximum sensing capacity given different materials and opening sizes. It is demonstrated that the use of a cavity, whether it is made of plastic or metal, can significantly enhance the sensing capacity and the point spread function of a focused beam. The imaging performance is also improved in terms cross-range resolution when compared to the no-cavity case.

Preliminary Results of a New Auxiliary Mechatronic Near-Field Radar System to 3D Mammography for Early Detection of Breast Cancer.

Accurate and early detection of breast cancer is of high importance, as it is directly associated with the patients' overall well-being during treatment and their chances of survival. Uncertainties in current breast imaging methods can potentially cause two main problems: (1) missing newly formed or small tumors; and (2) false alarms, which could be a source of stress for patients. A recent study at the Massachusetts General Hospital (MGH) indicates that using Digital Breast Tomosynthesis (DBT) can reduce the number of false alarms, when compared to conventional mammography. Despite the image quality enhancement DBT provides, the accurate detection of cancerous masses is still limited by low radiological contrast (about 1%) between the fibro-glandular tissue and affected tissue at X-ray frequencies. In a lower frequency region, at microwave frequencies, the contrast is comparatively higher (about 10%) between the aforementioned tissues; yet, microwave imaging suffers from low spatial resolution. This work reviews conventional X-ray breast imaging and describes the preliminary results of a novel near-field radar imaging mechatronic system (NRIMS) that can be fused with the DBT, in a co-registered fashion, to combine the advantages of both modalities. The NRIMS consists of two antipodal Vivaldi antennas, an XY positioner, and an ethanol container, all of which are particularly designed based on the DBT physical specifications. In this paper, the independent performance of the NRIMS is assessed by (1) imaging a bearing ball immersed in sunflower oil and (2) computing the heat Specific Absorption Rate (SAR) due to the electromagnetic power transmitted into the breast. The preliminary results demonstrate that the system is capable of generating images of the ball. Furthermore, the SAR results show that the system complies with the standards set for human trials. As a result, a configuration based on this design might be suitable for use in realistic clinical applications.

Assessment of some cultural experimental methods to study the effects of antibiotics on microbial activities in a soil: An incubation study.

Oxytetracycline (OTC) and sulfamethoxazole (SMX) are two of most widely used antibiotics in livestock and poultry industry. After consumption of antibiotics, a major portion of these compounds is excreted through the feces and urine of animals. Land application of antibiotic-treated animal wastes has caused increasing concern about their adverse effects on ecosystem health. In this regard, inconsistent results have been reported regarding the effects of antibiotics on soil microbial activities. This study was conducted based on the completely randomized design to the measure microbial biomass carbon, cumulative respiration and iron (III) reduction bioassays. Concentrations of OTC and SMX including 0, 1, 10, 25, 50, and 100 mg/kg were spiked in triplicate to a sandy loam soil and incubated for 21 days at 25°C. Results showed that the effects of OTC and SMX antibiotics on cumulative respiration and microbial biomass carbon were different. SMX antibiotic significantly affected soil microbial biomass carbon and cumulative respiration at different treatments compared to control with increasing incubation time. OTC antibiotic, on the other hand, negatively affected cumulative respiration compared to control treatment throughout the incubation period. Although OTC antibiotic positively affected microbial biomass carbon at day one of incubation, there was no clear trend in microbial biomass carbon between different treatments of this antibiotic after that time period. Nevertheless, sulfamethoxazole and oxytetracycline antibiotics had similar effects on iron (III) reduction such that they considerably affected iron (III) reduction at 1 and 10 mg/kg, and iron (III) reduction was completely inhibited at concentrations above 10 mg/kg. Hence, according to our results, microbial biomass carbon and cumulative respiration experiments are not able alone to exhibit the effect of antibiotics on soil microbial activity, but combination of these two experiments with iron (III) reduction test could well display the effects of sulfamethoxazole (SMX) and oxytetracycline (OTC) antibiotics on soil biochemical activities.

Preliminary imaging results and SAR analysis of a microwave imaging system for early breast cancer detection.

Currently X-ray-based imaging systems suffer from low contrast between malignant and healthy fibrous tissues in breast. Microwave Near-field Radar Imaging (NRI) shows a higher contrast between the aforementioned tissues and therefore can enhance tumor detection and diagnosis accuracy. In this work, we present the first imaging results of our developed NRI system that is equipped with a pair of Antipodal Vivaldi Antennas. We used a metal bearing ball immersed in oil as our object of interest, to keep the first measurement configuration simple. Moreover, to demonstrate the safety of our system for human subject tests, we simulated the Specific Absorption Rate (SAR) in a realistic breast tissue model and compared the resulted values with both the USA and Europe standards. The results show that firstly the imaging results from the measurements and simulations are comparable, and secondly the antennas radiations meet the SAR criteria.