Immunopathogenesis of multiple sclerosis: molecular and cellular mechanisms and new immunotherapeutic approaches.

Background: Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating autoimmune disease with increasing global prevalence. It predominantly affects females, especially those of European descent. The interplay between environmental factors and genetic predisposition plays a crucial role in MS etiopathogenesis.Methods: We searched recent relevant literature on reputable databases, which include, PubMed, Embase, Web of Science, Scopus, and ScienceDirect using the following keywords: multiple sclerosis, pathogenesis, autoimmunity, demyelination, therapy, and immunotherapy.Results: Various animal models have been employed to investigate the MS etiopathogenesis and therapeutics. Autoreactive T cells within the CNS recruit myeloid cells through chemokine expression, leading to the secretion of inflammatory cytokines driving the MS pathogenesis, resulting in demyelination, gliosis, and axonal loss. Key players include T cell lymphocytes (CD4+ and CD8+), B cells, and neutrophils. Signaling dysregulation in inflammatory pathways and the immunogenetic basis of MS are essential considerations for any successful therapy to MS. Data indicates that B cells and neutrophils also have significant roles in MS, despite the common belief that T cells are essential. High neutrophil-to-lymphocyte ratios correlate with MS severity, indicating their contribution to disease progression. Dysregulated signaling pathways further exacerbate MS progression.Conclusion: MS remains incurable, but disease-modifying therapies, monoclonal antibodies, and immunomodulatory drugs offer hope for patients. Research on the immunogenetics and immunoregulatory functions of gut microbiota is continuing to provide light on possible treatment avenues. Understanding the complex interplay between genetic predisposition, environmental factors, and immune dysregulation is critical for developing effective treatments for MS.

Secretome-based acellular therapy of bone marrow-derived mesenchymal stem cells in degenerative and immunological disorders: A narrative review.

The bone marrow (BM) plays a pivotal role in homeostasis by supporting hematopoiesis and immune cells' activation, maturation, interaction, and deployment. "BMSC-derived secretome" refers to the complete repertoire of secreted molecules, including nucleic acids, chemokines, growth factors, cytokines, and lipids from BM-derived mesenchymal stem cells (BMSCs). BMSC-derived secretomes are the current molecular platform for acellular therapy. Secretomes are highly manipulable and can be synthesised in vast quantities using commercially accessible cell lines in the laboratory. Secretomes are less likely to elicit an immunological response because they contain fewer surface proteins. Moreover, the delivery of BMSC-derived secretomes has been shown in numerous studies to be an effective, cell-free therapy method for alleviating the symptoms of inflammatory and degenerative diseases. As a result, secretome delivery from BMSCs has the same therapeutic effects as BMSCs transplantation but may have fewer adverse effects. Additionally, BMSCs' secretome has therapeutic promise for organoids and parabiosis studies. This review focuses on recent advances in secretome-based cell-free therapy, including its manipulation, isolation, characterisation, and delivery systems. The diverse bioactive molecules of secretomes that successfully treat inflammatory and degenerative diseases of the musculoskeletal, cardiovascular, nervous, respiratory, reproductive, gastrointestinal, and anti-ageing systems were also examined in this review. However, secretome-based therapy has some unfavourable side effects that may restrict its uses. Some of the adverse effects of this modal therapy were briefly mentioned in this review.

Design and Synthesis of N-Doped Porous Carbons for the Selective Carbon Dioxide Capture under Humid Flue Gas Conditions.

The design of novel porous solid sorbents for carbon dioxide capture is critical in developing carbon capture and storage technology (CCS). We have synthesized a series of nitrogen-rich porous organic polymers (POPs) from crosslinking melamine and pyrrole monomers. The final polymer's nitrogen content was tuned by varying the melamine ratio compared to pyrrole. The resulting polymers were then pyrolyzed at 700 °C and 900 °C to produce high surface area nitrogen-doped porous carbons (NPCs) with different N/C ratios. The resulting NPCs showed good BET surface areas reaching 900 m2 g-1. Owing to the nitrogen-enriched skeleton and the micropore nature of the prepared NPCs, they exhibited CO2 uptake capacities as high as 60 cm3 g-1 at 273 K and 1 bar with significant CO2/N2 selectivity. The materials showed excellent and stable performance over five adsorption/desorption cycles in the dynamic separation of the ternary mixture of N2/CO2/H2O. The method developed in this work and the synthesized NPCs' performance towards CO2 capture highlight the unique properties of POPs as precursors for synthesizing nitrogen-doped porous carbons with a high nitrogen content and high yield.

"I Would Rather Take the Vaccine Than Undergo Weekly Testing": Correlates of Health Workers' Support for COVID-19 Vaccine Mandates.

This study examined the support for vaccine mandates and uptake among clinical and non-clinical staff at a tertiary hospital in northern Nigeria, focusing on variation of survey responses based on job position, socio-demographic characteristics, and perceived risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Using an explanatory, sequential, mixed-methods design and deploying a pragmatic paradigm, 370 healthcare workers were administered structured questionnaires. This was followed by in-depth interviews with a sub-sample of respondents to further clarify the responses regarding support for the coronavirus disease 2019 (COVID-19) vaccine mandate. Findings demonstrated that less than one-half of respondents supported the COVID-19 mandate, and only one in three had received the recommended COVID-19 vaccine doses. Support for the vaccine mandate and vaccine uptake were predicted by profession, work experience, number of children, health status, and risk perception. Support for the vaccine mandate was ascribed to ethical and professional duty, whereas opposition was associated with respect for autonomy and human rights. This study documents the need to enhance support for vaccine mandates and uptake among healthcare workers through sustainable strategies, as Nigeria's healthcare workers are considered a source of trust and role models for the rest of society.

Maggot debridement therapy and complementary wound care: a case series from Nigeria.

OBJECTIVE: Maggot debridement therapy (MDT) is an emerging procedure involving the application of sterile maggots of the Dipteran species (commonly Lucilia sericata) to effect debridement, disinfection and promote healing in wounds not responding to antimicrobial therapy. Data on MDT in sub-Saharan Africa (including Nigeria) are scarce. This study aimed to use medicinal grade maggots as a complementary method to debride hard-to-heal necrotic ulcers and thereby promote wound healing. METHOD: In this descriptive study, we reported on the first group of patients who had MDT at Aminu Kano Teaching Hospital (AKTH), a tertiary hospital in northern Nigeria. The first instar larvae of Lucilia sericata were applied using the confinement (free-range) maggot therapy dressing method under aseptic conditions. RESULTS: Diabetic foot ulcer (DFU) grade III-IV constituted more than half of the wounds (53.3%), followed by necrotising fasciitis (30%), and post-traumatic wound infection (10%). Others (6.7%, included pyomyositis, surgical site infection and post traumatic wound infection). The median surface area of the wounds was 56cm2. Of the 30 patients, half (50%) had two MDT cycles with a median time of four days. Of the wounds, 22 (73%) were completely debrided using maggots alone while eight (27%) achieved complete debridement together with surgical debridement. Wound culture pre-MDT yielded bacterial growth for all the patients and Staphylococcus aureus was the predominant isolate in 17 wounds (56.7%) while Pseudomonas aeruginosa and Streptococcus pyogenes were predominant in five wounds (16.7%) each. Only four (13.3%) wound cultures yielded bacterial growth after MDT, all Staphylococcus aureus. CONCLUSION: A good prognosis was achieved post-MDT for various wounds. MDT effectively debrides and significantly disinfects wounds involving different anatomical sites, thus enhancing wound healing and recovery. MDT is recommended in such wounds.

Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach.

Several studies have shown that interleukin 6 (IL-6) is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory activity, depending on the immune response context. Macrophages are among several cells that secrete IL-6, which they express upon activation by antigens, subsequently inducing fever and production of acute-phase proteins from the liver. Moreover, IL-6 induces the final maturation of B cells into memory B cells and plasma cells as well as an adaptive role for short-term energy allocation. Activation of IL-6 receptors results in the intracellular activation of the JAK/STAT pathway with resultant production of inflammatory cytokines. Several mechanisms-controlled IL-6 expression, but aberrant production was shown to be crucial in the pathogenesis of many diseases, which include autoimmune and chronic inflammatory diseases. IL-6 in combination with transforming growth factor ß (TGF-ß) induced differentiation of naïve T cells to Th17 cells, which is the cornerstone in autoimmune diseases. Recently, IL-6 secretion was shown to form the backbone of hypercytokinemia seen in the Coronavirus disease 2019 (COVID-19)-associated hyperinflammation and multiorgan failure. There are two classes of approved IL-6 inhibitors: anti-IL-6 receptor monoclonal antibodies (e.g., tocilizumab) and anti-IL-6 monoclonal antibodies (i.e., siltuximab). These drugs have been evaluated in patients with rheumatoid arthritis, juvenile idiopathic arthritis, cytokine release syndrome, and COVID-19 who have systemic inflammation. JAK/STAT pathway blockers were also successfully used in dampening IL-6 signal transduction. A better understanding of different mechanisms that modulate IL-6 expression will provide the much-needed solution with excellent safety and efficacy profiles for the treatment of autoimmune and inflammatory diseases in which IL-6 derives their pathogenesis.

Determination of dermatophytes isolated from tinea capitis using conventional and ITS-based sequencing methods in Kano, Nigeria.

BACKGROUND: Tinea capitis is a dermatophyte infection of the scalp and hair that affects a large number of people worldwide. The disease commonly affects children and manifests with varying degrees of hair loss, scalp inflammation, and psychosocial impact. In Nigeria, the burden of tinea capitis is worrisome affecting over 15,000,000 school-age children. Molecular techniques complement the conventional mycological examinations in laboratory diagnosis of tinea capitis. In this study, we identified dermatophytes species causing tinea capitis in Kano, Nigeria, using ITS-based nucleotide sequencing technique in addition to conventional mycological examination. METHODS: We collected 112 samples from the scalp of children with clinically diagnosed tinea capitis at the dermatology clinic of Murtala Muhammad Specialist Hospital, Kano, between April and September 2019. The samples were processed and subjected to direct microscopy and mycological culture to isolate dermatophytes species that were identified morphologically and using ITS sequencing. RESULTS: Out of the 112 patients investigated, the majority (59.8%) were between the ages 6 and 9 years with a mean age of 7.3 ± 1.9 years. Males (79.5%) were predominantly affected. Black dot (46.4%) was the most common clinical type of tinea capitis followed by gray patch (39.3%) and kerion (1.8%). Favus was not observed. Microsporum audouinii (45.7%) was the predominant etiologic agent followed by Trichophyton soudanense (28.6%), T. violaceum (22.9%), and T. tonsurans (2.9%). CONCLUSION: The prominence of anthropophilic dermatophytes as the main causes of tinea capitis in our localities suggests that public health interventions to promote health education and good hygiene practices would minimize the transmission rate of tinea capitis among children in the study area.

Interleukin-10 Gene Promoter Polymorphisms and Susceptibility to Asthma: Systematic Review and Meta-analysis.

Several studies have previously assessed the association between interleukin (IL)-10 gene polymorphisms and the risk of asthma, leading to conflicting results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of the IL-10 gene rs1800896, rs1800871, and rs1800872 single-nucleotide polymorphisms (SNPs) and susceptibility to asthma. A systematic literature search performed until April 2020, and the pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to determine the association strength. Thirty articles comprising 5678 asthmatic patients and 6079 controls met the inclusion criteria. No significant association was found between rs1800872 SNP and susceptibility to asthma across all genetic models in the overall and subgroup analyses. The rs1800871 SNP had only significant association with a decreased risk of asthma in Europeans (OR 0.66, CI 0.53-0.82, P < 0.001). However, rs1800896 SNP was significantly associated with a decreased risk of asthma by dominant (OR 0.67, CI 0.50-0.90, P < 0.001) and heterozygote (OR 0.66, CI 0.49-0.88, P < 0.001) models in the overall analysis. Subgroup analyses indicated significant association of rs1800896 SNP by dominant (OR 0.45, CI 0.28-0.72, P < 0.001) and heterozygote (OR 0.43, CI 0.26-0.70, P < 0.001) models in the African population. The IL-10 rs1800896 SNP confers protection against the risk of asthma, especially in Africans. Additionally, rs1800871 SNP has a protective role against asthma in Europeans.

Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications.

BACKGROUND: Previous studies evaluated the association of IL-4 C33T polymorphism and risk of bronchial asthma but failed to establish a consistent conclusive association. In the present meta-analysis, we intend to define a more reliable estimate of the association in the presence of filling published literature. METHODS: An exhaustive search in Web of Science, Scopus, and PubMed databases was performed to identify all relevant publications before September 2020, and 24 publications (28 studies) with 6587 cases and 8408 controls were included in final analysis. The association between polymorphism and risk of asthma were measured by Odd ratios (ORs) and 95% confidence intervals (CIs). Moreover, Cochran's Q and the I2 statistics were used to evaluate the degree of heterogeneity between studies. RESULTS: In the overall study populations, a significant positive association was detected under all genotype models and announced the IL-4 C33T polymorphism as a potential risk factor in the pathogenesis of asthma. In the subgroup analysis by age, a significant association between IL-4 C33T polymorphism and risk of asthma in different age groups was identified in allelic model, which highlighted the predisposing role of the T allele for the asthma risk in all three age groups. Furthermore, the results of subgroup analysis by continent were heterogenous. Accordingly, IL-4 C33T polymorphism was a risk factor in Europeans (all models except heterozygote comparison), Americans (all models except recessive and homozygote comparison) and Asians (just recessive and allelic model). Finally, the ethnicity-specific analysis disclosed a significant association between IL-4 C33T polymorphism and asthma risk in Caucasians (all genotype models except heterozygote comparison), while this association was not significant in African-Americans. CONCLUSIONS: This study suggests that IL-4 C33T polymorphism potentially acts as a risk factor for asthma in different ethnicities and age groups.

Delivery of genome editing tools: A promising strategy for HPV-related cervical malignancy therapy.

INTRODUCTION: Persistent high-risk human papillomavirus infection is the main cause of various types of cancer especially cervical cancer. The E6 and E7 oncoproteins of HPV play critical roles in promoting carcinogenesis and cancer cell growth. As a result, E6 and E7 oncogenes are considered as promising therapeutic targets for cervical cancer. Recently, the development of genome-editing technologies including transcription activator-like effector nucleases (TALEN), meganucleases (MNs), zinc finger nucleases (ZFN), and more importantly clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) has sparked a revolution in the cervical cancer-targeted therapy. However, due to immunogenicity, off-target effect, renal clearance, guide RNA (gRNA) nuclease degradation, and difficult direct transportation into the cytoplasm and nucleus, the safe and effective delivery is considered as the Achilles' heel of this robust strategy. AREAS COVERED: In this review, we discuss cutting-edge available strategies for in vivo delivery of genome-editing technologies for HPV-induced cervical cancer therapy. Moreover, the combination of genome-editing tools and other therapies has been fully discussed. EXPERT OPINION: The combination of nanoparticle-based delivery systems and genome-editing tools is a promising powerful strategy for cervical cancer therapy. The most significant limitations of this strategy that need to be focused on are low efficiency and off-target events.