Cross-polarization magic-angle spinning solid-state NMR spectroscopy has been used to investigate the dependence of 13 C sugar chemical shifts on specific conformational parameters of a variety of ribonucleotides and ribonucleosides. Solid-state NMR is a valuable tool for nucleoside and nucleotide structural studies since it provides the means to acquire spectra that correspond to single conformations, as opposed to 13 C solutionNMRmethods. The distinct effects of sugar puckering on the C1′, C4′, and C5′ resonances of C2′ endo (S type) and C3′ endo (N type) furanoid conformations allow us to separate them into two groups. Further analysis of each group reveals an additional dependence of the C1′ and C5′ resonances on the glycosidic and C4′-C5′ exocyclic torsion angles, respectively. However, it is found that the glycosidic conformation cannot independently be determined from sugar 13 C chemical shift data. The statistical methods of exploratory data analysis and discriminant analysis are used to construct two canonical coordinates-linear combinations of chemical shifts which give the statistically optimal determination of the conformation from the NMR data.

Background: Ceftriaxone is one of the most common types of antibiotics used to treat most deadly bacterial infections. One way to alleviate the side effects of medication is to reduce drug consumption by changing the ordinary drug forms into nanostructured forms. In this study, a nanostructured lipid carrier (NLC) containing hydrophilic ceftriaxone sodium drug is developed, and its effect on eliminating gram-negative bacteria Escherichia coli death is investigated.Methods: Double emulsion solvent evaporation method is applied to prepare NLC. Mathematical modeling based on the solubility study is performed to select the best materials for NLC preparation. Haftyzer-Van Krevelen and Hoy's models are employed for this purpose. Drug release from optimized NLC is examined under in vitro environment. Then, the efficacy of the optimized sample on eliminating gram-negative bacteria Escherichia coli is investigated. Results: Mathematical modeling reveals that both methods are capable of predicting drug encapsulation efficiency trends by chaining solid and liquid lipids. However, Haftyzer-Van Krevelen's method can precisely predict the particle size trend by changing the surfactant types in water and oily phases of emulsions. The optimal sample has a mean particle size of 86 nm and drug entrapment efficiency of 83%. Also, a controlled drug release in prepared nanostructures over time is observed under in-vitro media. The results regarding the effectiveness of optimized NLC in killing Escherichia coli bacteria suggests that by cutting drug dosage of the nanostructured form in half, an effect comparable to that of free drug can be observed at longer times. Conclusion: Results confirm that NLC structure is an appropriate alternative for the delivery of ceftriaxone drug with a controlled release behavior.

Coronavirus disease 2019 (COVID‐19) is the seventh member of the bat severe acute respiratory syndrome family. COVID‐19 can fuse their envelopes with the host cell membranes and deliver their genetic material. COVID‐19 attacks the respiratory system and stimulates the host inflammatory responses, enhances the recruitment of immune cells, and promotes angiotensin‐converting enzyme 2 activities. Patients with confirmed COVID‐19 may have experienced fever, dry cough, headache, dyspnea, acute kidney injury, acute respiratory distress syndrome, and acute heart injury. Several strategies such as oxygen therapy, ventilation, antibiotic or antiviral therapy, and renal replacement therapy are commonly used to decrease COVID‐19‐associated mortality. However, these approaches may not be good treatment options. Therefore, the search for an alternative‐novel therapy is urgently important to prevent the disease progression. Recently, microRNAs (miRNAs) have emerged as a promising strategy for COVID‐19. The design of oligonucleotide against the genetic material of COVID‐19 might suppress virus RNA translation. Several previous studies have shown that host miRNAs play an antiviral role and improve the treatment of patients with COVID‐19. miRNAs by binding to the 3′‐untranslated region (UTR) or 5′‐UTR of viral RNA play an important role in COVID‐19‐host interplay and viral replication. miRNAs interact with multiple pathways and reduce inflammatory biomarkers, thrombi formation, and tissue damage to accelerate the patient outcome. The information in this review provides a summary of the current clinical application of miRNAs for the treatments of patients with COVID‐19.

During the last years, several strategies have been made to obtain mature erythrocytes or red blood cells (RBC) from the bone marrow or umbilical cord blood (UCB). However, UCB-derived hematopoietic stem cells (HSC) are a limited source and in vitro large-scale expansion of RBC from HSC remains problematic. One promising alternative can be human pluripotent stem cells (PSCs) that provide an unlimited source of cells. Human PSCs, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are self-renewing progenitors that can be differentiated to lineages of ectoderm, mesoderm, and endoderm. Several previous studies have revealed that human ESCs can differentiate into functional oxygen-carrying erythrocytes; however, the ex vivo expansion of human ESC-derived RBC is subjected to ethical concerns. Human iPSCs can be a suitable therapeutic choice for the in vitro/ex vivo manufacture of RBCs. Reprogramming of human somatic cells through the ectopic expression of the transcription factors (OCT4, SOX2, KLF4, c-MYC, LIN28, and NANOG) has provided a new avenue for disease modeling and regenerative medicine. Various techniques have been developed to generate enucleated RBCs from human iPSCs. The in vitro production of human iPSC-derived RBCs can be an alternative treatment option for patients with blood disorders. In this review, we focused on the generation of human iPSC-derived erythrocytes to present an overview of the current status and applications of this field.

, is a causative agent of morbidity and mortality in immunocompromised and congenitally-infected individuals. Attempts to construct DNA vaccines against using surface proteins are increasing. The dense granule antigens are highly expressed in the acute and chronic phases of infection and considered as suitable DNA vaccine candidates to control toxoplasmosis. In the present study, bioinformatics tools and online software were used to predict, analyze and compare the structural, physical and chemical characters and immunogenicity of the GRA-1, GRA-4, GRA-6 and GRA-7 proteins. Sequence alignment results indicated that the GRA-1, GRA-4, GRA-6 and GRA-7 proteins had low similarity. The secondary structure prediction demonstrated that among the four proteins, GRA-1 and GRA-6 had similar secondary structure except for a little discrepancy. Hydrophilicity/hydrophobicity analysis showed multiple hydrophilic regions and some classical high hydrophilic domains for each protein sequence. Immunogenic epitope prediction results demonstrated that the GRA-1 and GRA-4 epitopes were stable and GRA-4 showed the highest degree of antigenicity. Although the GRA-7 epitope had the highest score of immunogenicity, this epitope was instable and had the lowest degree of antigenicity and half-time in eukaryotic cell. Also, the results indicated that GRA4-GRA7 epitope and GRA6-GRA7 had the highest degree of antigenicity and immunogenicity among multi-hybrid epitopes, respectively. Totally, in the present study, single epitopes showed the highest degree of antigenicity compared with multi-hybrid epitopes. Given the results, it can be concluded that GRA-4 and GRA-7 can be powerful DNA vaccine candidates against .