Immunoglobulin E (IgE) serves a crucial role in the pathogenesis of several allergic disorders, and elevated levels of total serum IgE have been associated with asthma. IgE is responsible for the release of several asthma‑associated inflammatory mediators from mast cells, such as histamine and prostaglandins. The aim of the present study was to assess the association of interleukin (IL)‑13 single nucleotide polymorphism (SNP) rs20541 and forkhead box O3a (FOXO3a) SNP rs13217795 with IgE levels in asthmatic patients and a healthy control group. Genetic polymorphism analysis of SNPs was performed using PCR/restriction fragment length polymorphism. Total serum IgE levels were measured using an ELISA kit. Genotypes were grouped into three models: Co‑dominant, dominant and recessive. Major and minor alleles for IL‑13 SNP rs20541 and FOXO3a SNP rs13217795 were C and T, whereas for IL‑13, they were G and A, respectively. There was a significant association between the IL‑13 rs20541 SNP and the total IgE serum levels, in which pure minor alleles were associated with a significant reduction (~5x lower) in IgE serum levels compared with the major alleles in asthmatic subjects and to a lesser extent in the control subjects. Additionally, the FOXO3a rs13217795 SNP was associated with a significant increase in total IgE levels (~5x higher) in the asthmatic patients compared with the control subjects. In conclusion, the present study confirmed that there was a significant association between the IL‑13 SNP rs20541 and asthma, and an association between the FOXO3a SNP rs13217795 with asthma pathogenicity in Jordanian subjects.

Epstein–Barr virus (EBV) is a human virus with oncogenic potentials that is implicated in various human diseases and malignancies. In this study, the modulator activity of the potent herbal extract drug thymoquinone on EBV was assessed in vitro. Thymoquinone was tested for cytotoxicity on human cells of lymphoblastoid cells, Raji Burkitt’s lymphoma, DG-75 Burkitt’s lymphoma, peripheral blood mononuclear cells, and periodontal ligament fibroblast. Apoptosis induction was analyzed via TUNEL assay and activity studies of caspase-3. The effect of thymoquinone on EBV gene expression was determined using real-time polymerase chain reaction. We report here, for the first time, a promising selective inhibitory affect of thymoquinone on EBV-infected B cell lines in vitro, compared with lower activity on EBV negative B cell line and very low toxicity on human peripheral blood mononuclear cells and periodontal ligament fibroblasts. Moreover, the drug was found to efficiently suppress the RNA expression of EBNA2, LMP1, and EBNA1 genes. Specifically, EBNA2 expression levels were the most affected indicating that this gene might have a major contribution to thymoquinone potency against EBV infected cells. Overall, our results suggest that thymoquinone has the potential to suppress the growth of EBV-infected B cells efficiently.

Glioblastoma multiforme continues to be one of the most aggressive brain cancers, posing a serious health challenge, as it offers a median survival of only 15–23 months and a 5-year survival rate of less than 6%. Current treatments often prove inadequate, underscoring the urgency for new therapeutic strategies. This study investigated the potential of silencing the PFKFB4 and HMOX1 genes in U87-MG glioblastoma cells using small interfering RNAs (siRNAs), both alone and alongside the chemotherapeutic agents temozolomide (TMZ) and doxorubicin (DOX). Through MTT assays, qPCR, and wound healing techniques, we assessed cell viability, gene expression, and cell migration. Notably, siPFKFB4 enhanced DOX’s cytotoxic effect, reducing its IC₅₀ by six-fold, while having a milder impact with TMZ. When both siRNAs were combined with DOX, the IC₅₀ decreased by two-fold without harming normal cells. Although siHMOX1 reduced cell migration, it only modestly affected cell proliferation with either DOX or TMZ. The gene expression analysis demonstrated that the siPFKFB4/DOX treatment led to an upregulation of pro-apoptotic genes such as DPYSL4, while simultaneously downregulating anti-apoptotic genes, including BCL-2 and PARP2. In contrast, the siHMOX1 combination influenced the expression of 14 genes, significantly enhancing the levels of CYLD, FAS, and CASP3, which are key promoters of apoptosis. In migration assays, siPFKFB4/DOX and siHMOX1/DOX reduced cell migration by 65 and 75%, respectively. These findings suggest that siPFKFB4 combined with DOX offers a promising pathway for GBM therapy, advocating further exploration into effective central nervous system drug delivery methods.

Both opioids and cannabinoids have well-known antinociceptive effects in different animal models of chronic pain. However, unwanted side effects limit their use. The aim of this study is to evaluate the antinociceptive effect of combining synthetic cannabinoids with subtherapeutic doses of opioids, and to evaluate the effects of these drugs/combinations on rat’s locomotor activity. Intra-plantar injection of Complete Freund’s Adjuvant (CFA) into the left hindpaw and intraperitoneal injection of streptozotocin (STZ) were used to induce inflammatory and diabetic neuropathic pain in adult male Sprague-Dawley rats, respectively. Von Frey filaments were used to assess the antinociceptive effects of opioids (morphine and tramadol) and the synthetic cannabinoids (HU210 and WIN55212) or their combinations on CFA and STZ-induced mechanical allodynia. Open field test was used to evaluate the effect of these drugs or their combinations on locomotion. HU210 and WIN55212 did not produce significant antinociceptive effect on inflammatory pain while only the maximal dose of HU210 (1 mg/kg) was effective in neuropathic pain. Only the maximal doses of morphine (3.2 mg/kg) and tramadol (10 mg/kg) had significant anti-allodynic effects in both models. Tramadol (1 mg/kg) enhanced the antinociceptive effects of WIN55212 but not HU210 in neuropathic pain with no effect on inflammatory pain. However, in open field test, the aforementioned combination did not change tramadol-induced depression of locomotion. Tramadol and WIN55212 combination produces antinociceptive effects in neuropathic but not inflammatory pain at low doses with no additional risk of locomotor impairment, which may be useful in clinical practice.

Background: The growing dissatisfaction with the available traditional chemotherapeutic agents has enhanced the need to develop new methods for obtaining materials with more effective and safe anti-cancer properties. Over the past few years, the usage of metallic nanoparticles has been a target for researchers of different scientific and commercial fields due to their tiny sizes, environment-friendly properties, and a wide range of applications. To overcome the obstacles of traditional physical and chemical methods for the synthesis of such nanoparticles, a new, less expensive, and eco-friendly method has been adopted using natural existing organisms as a reducing agent to mediate the synthesis of the desired metallic nanoparticles from their precursors, a process called green biosynthesis of nanoparticles. Objective: In the present study, zinc-iron bimetallic nanoparticles (ZnFe₂O₄) were synthesized via an aqueous extract of Boswellia carteri resin mixed with zinc acetate and iron chloride precursors, and they were tested for their anticancer activity. Methods: Various analytic methods were applied for the characterization of the phyto synthesized ZnFe₂O₄, and they were tested for their anticancer activity against MDA-MB-231, K562, MCF-7 cancer cell lines, and normal fibroblasts. Results: Our results demonstrate the synthesis of cubic structured bimetallic nanoparticles ZnFe₂O₄ with an average diameter of 10.54 nm. MTT cytotoxicity assay demonstrates that our phyto-synthesized ZnFe₂O₄ nanoparticles exhibited a selective and potent anticancer activity against K562 and MDA-MB-231 cell lines with IC50 values 4.53 μM and 4.19 μM, respectively. Conclusion: In conclusion, our biosynthesized ZnFe₂O₄ nanoparticles show a promising, environmentally friendly, and low coast chemotherapeutic approach against selective cancers with a predicted low adverse side effect toward normal cells. Further, in vivo, advanced animal research should be done to execute their applicability in living organisms.