Background: Monkeypox virus (MPXV) is a zoonotic pathogen that influences humans as well as animalsposing a significant public health concern due to its emergence and circulation. The structural dynamics and features of several MPXV proteins, including M1R, have not been completely studied.

Methods: This experiment focuses on the prediction and analysis of the secondary and tertiary constructs for the M1R protein. Briefly, its amino acid sequence was collected from the UniProt database. A wide range of in silico approaches were employed, including ProtParam, SOPMA, PSIPRED, CD Search, GalaxyTMB, Robetta, I-TASSER, and GROMACS, in order to explore the physicochemical properties, structural features, and functional insights of the M1R protein. The tertiary structure models were evaluated to detect the most reliable solution, which was then used for Immunoinformatics analyses such as MHC I/II and B-cell epitope prediction using the IEDB and Ellipro tools, respectively. Epitopes from the M1R protein were evaluated based on antigenicity, affinity of binding, along solubility. Furthermore, active sites were forecast by the CASTp v3.0 tool. 

Results: Physicochemical calculations indicate that M1R had favorable thermostability and hydrophilic features. Structural analyses suggested that M1R is a lipid membrane protein component of DNA viruses, suggesting it as a robust antigenic target. Immunogenicity analyses indicated it as a potentially suitable target for immunogenic protein design. As well, molecular dynamics simulations (MDS) were carried out for 100-ns using an all-atom forcefield. Analysis of various molecular dynamics parameters of M1R throughout the MDS trajectory, including RMSD, RMSF, radius of gyration (Rg), and solvent accessible surface area (SASA), indicated good stability of the M1R and unveiled important molecular dynamics characteristics such as the flexibility of certain protein regions.

Conclusion: Multiple epitopes were detected in our experiment, with 12 B-cell epitopes identified using the Robetta model and 6 B-cell epitopes predicted by the Galaxy model, alongside 3 MHC-I and 3 MHC-II epitopes, which scored favorably. Results of the present computational analysis provide clues to unleash the potential of M1R as an immunotherapy target for the development of antiviral solutions against MPXV in the future.

Background: Allergic rhinosinusitis (ARS) and chronic allergic otitis media are common manifestations of upper airway allergic inflammation. Despite advances in understanding the immunopathogenesis of these conditions, hematological markers reflecting systemic immune activation remain underexplored, particularly in combined presentations. To evaluate hematological parameters, with emphasis on leukocyte subpopulations and the eosinophil-lymphocytic index, in patients with allergic rhinosinusitis combined with chronic allergic otitis media compared to non-allergic chronic otitis media.

Methods: A retrospective analysis was conducted on 60 patient records from the otorhinolaryngology department of the National Medical Center “Shifobakhsh”, Republic of Tatarstan. Group I (n=30) included patients with allergic rhinosinusitis and chronic allergic otitis media; Group II (n=30), serving as controls, had chronic otitis media without allergic manifestations. Complete blood count (CBC) with differential was analyzed, and the eosinophil-lymphocytic index was calculated. Data were compared using descriptive statistics and correlation analysis.

Results: Patients with allergic rhinosinusitis and chronic allergic otitis media showed a relative increase in eosinophils and higher incidence of peripheral eosinophilia. Relative lymphocytosis was observed in 40% of Group I versus 16.7% in controls. The ELI was elevated in 43.3% of allergic patients. Leukocytosis was present in 16.7% of Group I and 40% of Group II. Absolute lymphocyte count was significantly lower in Group I. Correlation analysis revealed stable, strong relationships between segmented neutrophils and eosinophils, as well as neutrophils and monocytes, suggesting shared immunological pathways.

Conclusion: Hematological changes, particularly eosinophilia and elevated eosinophil-lymphocytic index, serve as indirect markers of systemic allergic sensitization in patients with combined Allergic rhinosinusitis and chronic allergic otitis media. While not diagnostic alone, these parameters may support clinical suspicion and reduce reliance on extensive allergological testing in resource-limited settings.

Monkeypox virus (MPXV) is a novel virus that has been disseminated around the globe and caused human disease. Over 86 thousand infection cases have been reported, which has concerned the World Health Organization (WHO). Given the challenges faced due to the spread of MPXV, an immune-mediating therapy to prevent infection by MPXV is invaluable to aid large-scale public health practices. In this field, the mRNA vaccine could be a sufficient way to control the virus's transmissibility around worldwide study; we used immunoinformatic approaches that aided the pathway to develop the novel mRNA vaccine. In the first step, we gathered three key proteins (A35R, cell surface binding, and M1R) conserved in Cowpox as well as Vaccinia viruses for the design of vaccines and computed the potent immunogen epitopes that the engineered vaccines assemble with the fused finalized epitopes and Beta-defensin 3 adjuvant that is a major stimulation of dendritic cells (DCs), along with the PADRE and TAT sequences were added. The vaccine construct was modeled with Robetta tool and validated by PROCHECK, ERRAT, and Z-score. Physicochemical properties were also investigated and confirmed to be favorable. Disulfide engineering, immunological simulation, and molecular docking with TLR3 were performed. Finally, the construction of mRNA was designed in silico, the mRNA vaccine structure was predicted, and then the molecular dynamics simulation was performed to investigate the TLR3-vaccine complex. The eighteen final epitopes were predicted. The engineered multi-epitope protein, entails 350 amino acids and had good structural quality, as quantified through an ERRAT value over 99%. Also, engineering of disulfide bond was performed in order to augment the construct stability of the MPXV vaccine. The Ramachandran analysis was utilized to further corroborate the favorable φ (phi) and ψ (psi) angles, with the aminoacids localized to the highly favorable or permitted regions.  The design of the mRNA construct was achieved by incorporating the 5’UTR, start codon, signal peptide, open reading frames, stop codon,3’UTR, and polyA. In addition, the immune simulation showed sustained immune response. Also, the molecular dynamic simulation (MDS) and energy analyses suggested that the vaccine-TLR3 complex binding was stable. An mRNA vaccine was designed to provoke a robust immune response against MPXV while offering immunoprotection against Cowpox and Vaccinia. The present work analyzed the structure of a novel multi-epitope vaccine, which indicated it could be an effective option against MPXV infection. Future study is recommended to confirm the immunomodulatory role of the designed MPXV vaccine.

The peculiarity of the chromosomally integrated form of human herpesvirus type 6 (ciHHV-6) is its wide distribution (up to 1% of the population), the possibility of transmission by inheritance, the problem of diagnosis, including issues of differential diagnosis with the acute form of HHV-6 infection, which, in turn, makes it difficult to resolve the problem of the therapy necessity. In addition, activation of ciHHV-6 is possible sometimes with acute infection clinical symptoms and the need for antiviral therapy, especially in patients after bone marrow transplantation and chemotherapy. We report a 10-years-old girl after chiasmal-sellar germinoma surgery and subsequent chemotherapy with ciHHV-6B. The child was treated with ganciclovir. This did not significantly influence the reduction of the viral load HHV-6B DNA in serum and cerebrospinal fluid. No adverse effects of antiviral treatment were registered. It’s important to exclude ciHHV-6 before the diagnosis of HHV-6 active disease is made, as this screening may prevent the unnecessary use of antivirals.

Abstract

Background: Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease caused by mutations in the MEFV gene. These patients typically present with lymphocytosis and thrombocytosis during periods of inflammation; however, some patients may manifest leukopenia along with other symptoms.

Methods: Demographic data, medical history, laboratory data, and genetic findings of the cases were collected by reviewing clinical records of the patient. Whole-genome sequencing test revealed a mutation in MEFV gene. A systematic searched was conducted in four databases: PubMed, Web of Science, Scopus, and PerQuest, using keywords related to blood abnormalities in FMF disease.

Results: A mutation in the MEFV gene was confirmed in a 29-year-old patient with FMF. He experienced periodic and regular decreases in the number of neutrophils, lymphocytes, and platelets during periods of inflammation. Our literature review revealed neutropenia (17.6%), lymphopenia (8.8%), thrombocytopenia (11.8%), leukopenia (61.8%), and anemia (20.6%) are the frequent most common hematologic complications. Genetic analysis in 28 patients revealed M694V as the most prevalent mutation (57.1%), followed by E148Q (21.4%), M680I (10.7%), and others.

Conclusions: Reporting this case and others highlights that hematological manifestations in FMF can be observed periodic and simultaneous decreases in neutrophils, lymphocytes, and platelet counts can in patients with FMF.