Psoriasis, a persistent immune-mediated inflammatory skin condition, affects approximately 2-3% of the global population. Current treatments for psoriasis are fraught with limitations, including ...adverse effects, high costs, and diminishing efficacy over time. Thymoquinone (TQ), derived from Nigella sativa seeds, exhibits promising anti-inflammatory, antioxidant, and immunomodulatory properties that could prove beneficial in managing psoriasis. However, TQ’s hydrophobic nature and poor bioavailability have hindered its usefulness as a therapeutic agent. Recent research has strategically addressed these challenges by developing nano-thymoquinone (nano-TQ) formulations to enhance delivery and efficacy in treating psoriasis. Preclinical studies employing mouse models have demonstrated that nano-TQ effectively mitigates inflammation, erythema, scaling, epidermal thickness, and cytokine levels in psoriatic lesions. Various nano-TQ formulations, including nanoemulsions, lipid vesicles, nanostructured lipid carriers, and ethosomes, have been explored to improve solubility, facilitate skin penetration, ensure sustained release, and achieve site-specific targeting. Although clinical trials are currently scarce, the outcomes from in vitro and animal models are promising. The potential co-delivery of nano-TQ with other anti-psoriatic agents also presents avenues for further investigation.
Exosomes are extracellular vesicles characterized by their size, source, release mechanism and contents. MicroRNAs (miRNAs) are single stranded non-coding RNAs transcribed from DNA. Exosomes and ...miRNAs are widespread in eukaryotic cells, especially in mesenchymal stem cells (MSCs). MSCs are used for tissue regeneration, and also exert paracrine, anti-inflammatory and immunomodulatory effects. However, the use of MSCs is controversial, especially in the presence or after the remission of a tumor, due to their secretion of growth factors and their migration ability. Instead of intact MSCs, MSC-derived compartments or substances could be used as practical tools for diagnosis, follow up, management and monitoring of diseases. Herein, we discuss some aspects of exosomal miRNAs derived from MSCs in the progression, diagnosis and treatment of various diseases. Video Abstract.
Objective
Immune changes play fundamental roles in the pathogenesis and severity of coronavirus disease 2019 (COVID-19). Previous studies have revealed alterations in immune responses of patients ...with non-severe and severe COVID-19. Therefore, this study investigated whether interleukin-27 (IL-27) and interleukin-32 (IL-32) levels may be considered as predicting factors for determining the severity and outcome of COVID-19.
Methods
The blood samples were collected from 50 non-severe and severe patients infected with COVID-19 and 25 healthy subjects. The serum samples were isolated from the whole blood. The levels of IL-27 and IL-32 were measured by enzyme-linked immunosorbent assay and percentages of some immune cells were studied by cell counter.
Results
The levels of IL-27 and IL-32 were significantly higher in COVID-19 patients than healthy subjects (p < 0.0001–0.01). IL-27 was significantly reduced in severe COVID-19 patients who needed to undergo ICU therapy (p < 0.05). Disease severity was significantly associated with IL-27 level in patients with COVID-19 (p < 0.05), unlike IL-32 level. There was a significant association between IL-27 and IL-32 in participants (p < 0.0001, odds ratio (OR) = 0.9873; 95% confidence interval (CI) = 0.9998 to 1.000; p < 0.05, OR = 0.4462; 95% CI = 0.08,579 to 0.7802; p < 0.01, OR = 0.6640, 95% CI = 0.3007–0.8590). IL-27 level was significantly higher in the recovered subjects than dead cases (p < 0.0001). IL-27 and IL-32 levels in patients who had fever were significantly higher than those who did not have (p < 0.01–0.05), unlike patients who suffered from cough (p < 0.001–0.01). The IL-27 level in patients with non-severe COVID-19 was directly correlated with CRP value (p < 0.05, OR = 0.5,722,357, 95% CI = 0.06,807,176–0.8,435,928). IL-27 and IL-32 levels in non-severe patients were positively associated with NLR (p < 0.01, OR = 0.7292; 95% CI = 0.2809 to 0.9163; p < 0.01, OR = 0.6537, 95% CI = 0.1425–0.8896). Patients with severe COVID-19 had a significant increase in NLR (p < 0.0001–0.05). NLR was significantly correlated with the disease severity (p < 0.0001–0.05). Survivors had a significant reduction in NLR compared with those who succumbed to COVID-19 (p < 0.05).
Conclusion
Change in IL-27 level along with the frequencies of some immune cells may serve as a predictor of the severity and outcome of COVID-19.
Coronavirus disease 2019 (COVID-19), an acute respiratory infection, is largely associated with dysregulation and impairment of the immune system. This study investigated how the immune system ...changes were related to disease severity in COVID-19 patients. The frequencies of different immune cells and levels of pro- and anti-inflammatory cytokines in whole blood of participants were determined by flow cytometry and enzyme-linked immunosorbent assay, respectively. The values of other inflammatory agents were also studied. In the late recovery stage, unlike CD56high CD16+/− NK cells and monocytes, CD56low CD16+ NK cell numbers were increased (P < 0.0001–0.05). Th1, Th2, and Th17 cell percentages were significantly lower in patients than healthy control (P < 0.0001–0.05), while their frequencies were increased following disease recovery (P < 0.0001–0.05). The numbers of Tregs, activated CD4+ T cells, and exhausted CD8+ T cells were significantly decreased during a recovery (P < 0.0001–0.05). No significant change was observed in exhausted CD4+ T cell number during a recovery (P > 0.05). B cell showed an increased percentage in patients compared to healthy subjects (P < 0.0001–0.05), whereas its number was reduced following recovery (P < 0.0001–0.05). IL-1α, IL-1β, IL-6, TNF-α, and IL-10 levels were significantly decreased in the late recovery stage (P < 0.0001–0.05). However, TGF-β1 level was not significantly changed during the recovery (P > 0.05). Lymphocyte numbers in patients were significantly decreased (P < 0.001), unlike ESR value (P < 0.001). Lymphocyte number was negatively correlated to ESR value and Th2 number (P < 0.05), while its association with monocyte was significantly positive at the first day of recovery (P < 0.05). The immune system changes during the disease recovery to improve and regulate immune responses and thereby may associate with the reduction in disease severity.
MicroRNA-146a (miR-146a) is a regulator of inflammatory response. Periodontitis is a disease with immune pathophysiology of the periodontium in which the inflammation results in the destruction of ...the soft tissues and alveolar bone. Therefore, the aim of this study was to investigate the expressions of miR-146a, OPG, and RANKL in diseased and healthy periodontal tissues to understand whether miR-146a expression level may associate with OPG and RANKL mRNA levels and OPG/RANKL ratio after non-surgical periodontal treatment.
The levels of miR-146a, RANKL, and OPG in gingival tissues from patients with generalized periodontitis stages II and III and grades A and B (n = 15, group A), patients with generalized periodontitis stages III and IV and grade C (n = 15, group B), and healthy individuals (n = 10) were determined by real-time PCR. The associations of miR-146a expression with OPG and RANKL levels were evaluated.
The levels of miR-146a in two subgroups within periodontitis patients were significantly higher than healthy subjects (P < 0.0001). MiR-146a showed the increased level in group A of patients compared with group B (P < 0.05). Clinical parameters such as probing depth (PD) and clinical attachment loss (CAL) were significantly higher in patients than control group (P < 0.05). The levels of OPG and RANKL were increased in patients compared with healthy subjects, although the elevated levels were not statistically significant. MiR-146a was not associated with OPG and RANKL levels and OPG/RANKL ratio.
The results of this study failed to show the associations of miR-146a level with OPG and RANKL levels and OPG/RANKL ratio in periodontitis after non-surgical periodontal treatment.
Some failures in ovary function, like folliculogenesis and oogenesis, can give rise to various infertility-associated problems, including polycystic ovary syndrome (PCOS) and premature ovarian ...insufficiency (POI). PCOS influences 8 to 20% of women; while POI occurs in at least 1% of all women. Regrettably, the current therapies for these diseases have not sufficiently been effective, and finding a suitable strategy is still a puzzle. One of the helpful strategies for managing and treating these disorders is understanding the contributing pathogenesis and mechanisms. Recently, it has been declared that abnormal expression of microRNAs (miRNAs), as a subset of non-coding RNAs, is involved in the pathogenesis of reproductive diseases. Among the miRNAs, the roles of miRNA-21 in the pathogenesis of PCOS and POI have been highlighted in some documents; hence, the purpose of this mini-review was to summarize the evidences in conjunction with the functions of this miRNA and other effective microRNAs in the normal or abnormal functions of the ovary (i.e., PCOS and POI) with a mechanistic insight.
Programmed death-1 (PD-1), as an immunoinhibitory receptor encoded by
programmed cell death-1
(
PDCD1
) gene, has a pivotal role in tolerance to self-antigens. Mutations of
PDCD1
may participate in ...susceptibility to basal cell carcinoma (BCC) as the most common of skin cancer. We studied the impacts of two single nucleotide polymorphisms (SNPs) within
PDCD1
and their haplotypes in BCC susceptibility in an Iranian population. The blood samples were collected from 210 BCC and 220 healthy individuals. After the extraction of genomic DNA, the genotypes and alleles of PD1.1 G/A (rs36084323) and PD1.6 G/A (rs10204525) SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Four haplotypes were estimated by these SNPs. Our data revealed that genotype and allele frequencies of PD1.1 and PD1.6 polymorphisms in BCC patients were similar to those in healthy individuals. The results of estimated haplotypes for
PDCD1
indicated that GG and AA haplotypes of
PDCD1
had protective effects on BCC susceptibility (OR = 0.7, 95% CI = 0.51–0.96,
p
= 0.03 and OR = 0.57, 95% CI = 0.35–0.91,
p
= 0.02, respectively), while GA and AG haplotypes served as the risk factors for developing BCC (OR = 1.76, 95% CI = 1.09–2.84,
p
= 0.02 and OR = 3.87, 95% CI = 1.95–7.69,
p
= <0.001, respectively). Based on these findings, frequency distributions of
PDCD1
haplotypes have important roles in the determination of BCC development in the Iranian population. However, larger multicenter studies are required to confirm this conclusion.
Systemic lupus erythematous (SLE) disease is a chronic autoimmune disease with unknown etiology that can involve different organs. Polymorphisms in Fcγ receptors have been identified as genetic ...factors in susceptibility to SLE. This study was aimed to investigate effects of two single nucleotide polymorphisms (SNPs) within FcγRIIB and FcγRIIIA genes on systemic lupus erythematous disease activity index (SLEDAI) in an Iranian population.
Our findings indicated TT and GG genotypes were the common genotypes of FcγRIIB and FcγRIIIA SNPs in SLE patients, respectively. There were no significant differences in genotype and allele frequencies of FcγRIIB and FcγRIIIA SNPs in SLE and healthy subjects. However, the frequencies of genotypes and alleles of FcγRIIB and FcγRIIIA SNPs were significantly associated with some clinical manifestations used to determine SLEDAI (P < 0.001-0.5).
Type I hypersensitivity (allergic reaction) is an unsuitable or overreactive immune response to an allergen due to cross-link immunoglobulin E (IgE) antibodies bound to its high-affinity IgE ...receptors (FcεRIs) on effector cells. It is needless to say that at least two epitopes on allergens are required to the successful and effective cross-linking. There are some reports pointing to small proteins with only one IgE epitope could cross-link FcεRI-bound IgE through homo-oligomerization which provides two same IgE epitopes. Therefore, oligomerization of allergens plays an indisputable role in the allergenic feature and stability of allergens. In this regard, we review the signaling capacity of the B cell receptor (BCR) complex and cross-linking of FcεRI which results in the synthesis of allergen-specific IgE. This review also discusses the protein-protein interactions involved in the oligomerization of allergens and provide some explanations about the oligomerization of some well-known allergens, such as calcium-binding allergens, Alt a 1, Bet v 1, Der p 1, Per a3, and Fel d 1, along with the effects of their concentrations on dimerization.
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