The role of Interleukin-21 (IL-21) in allergic disorders: Biological insights and regulatory mechanisms.

In recent decades, allergic diseases subsequent from an IgE-mediated response to specific allergens have become a progressively public chronic disease worldwide. They have shaped an important medical and socio-economic burden. A significant proportion of allergic disorders are branded via a form 2 immune response relating Th2 cells, type 2 natural lymphoid cells, mast cells and eosinophils. Interleukin-21 (IL-21) is a participant of the type-I cytokine family manufactured through numerous subsets of stimulated CD4+ T cells and uses controlling properties on a diversity of immune cells. Increasingly, experimental sign suggests a character for IL-21 in the pathogenesis of numerous allergic disorders. The purpose of this review is to discuss the biological properties of IL-21 and to summaries current developments in its role in the regulation of allergic disorders.

Enhanced intramolecular charge transfer and near-infrared fluorescence in 4-dimethylamino-chalcone analogues through extended conjugation: synthesis, photophysical properties, and theoretical modelling.

The distinctive characteristics of near-infrared fluorescent organic molecules render them indispensable across diverse applications, from energy harvesting to bioimaging and sensing technologies. In this work, we continue our investigation on the chalcone derivative, 4-dimethylamino-2'-hydroxychalcone (nDHC, n = 1; where n is the number of olefinic bonds), by expanding the number of central double bonds (n = 2 (2DHC) and n = 3 (3DHC)). Additionally, we also synthesized the structurally related chalcones lacking the OH group (DC, 2DC, 3DC) in order to obtain a comprehensive understanding of their effects on the intramolecular charge transfer (ICT). The results show remarkable bathochromic shifts in absorption and fluorescence peaks in solution as n increases. These shifts, 20 nm and 35 nm for absorption and 100 nm and 200 nm for fluorescence in 2DHC and 3DHC, respectively, signify enhanced ICT and a significant increase in the excited state's dipole moment. The presence of OH groups notably amplifies these shifts due to additional electron donation, influencing solute-solvent interactions in solution. Femtosecond fluorescence upconversion and transient absoprtion techniques unraveled distinct dynamics in these derivatives, exhibiting the dominance of vibrational cooling, solvation, and intramolecular motions, particularly in the larger conjugated systems 3DHC and 3DC. The observed changes in the femtosecond transinet absorption spectra suggest the existence of new active states in extended conjugation systems, indicating diverse intramolecular conformational states contributing to their relaxation dynamics. The results of this study provide invaluable insights into excited-state spectroscopy, offering a roadmap for tailoring chalcone derivatives for specific applications.

Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation.

The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation.

The role of bee venom on immunological and hematological parameters in albino rats.

Bee venom (BV) showed therapeutical effects to treat various diseases as it contains at least 18 pharmacologically active components including various enzymes, peptides, and amines. This study aimed to evaluate the action of BV on some hematological parameters, humoral and cellular immunity, and the determination of antioxidant levels in male albino rats. The study included 40 male albino rats (190-210 g), divided into four groups. Three groups were injected subcutaneously with three different doses of BV (2.5, 5, and 10 mg/kg, respectively). The control group was injected with saline solution. Blood samples were obtained to measure total leucocytes count (TLC), differential leukocytes count, hematological parameters (hemoglobin (Hb), hematocrit (HCT), red blood cells (RBCs), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC) and Platelets. Sera were used to assess immunoglobulins (IgM, IgG, IgA, and IgE), some cytokines e.g., tumor necrosis factor-alpha (TNF-α), tumor growth factor beta (TGF-ß), interleukins 6 and 10 (IL-6, IL-10), and some antioxidant levels malondialdehyde (MDA), super oxide dismutase (SOD), and glutathione (GSH). Data showed that BV therapy increased antibody production levels (IgM, IgG, and IgA) while decreasing IgE levels. Hematological markers (Hb and lymphocytes) were increased. BV increased total TGF- ß and IL-10 but decreased total TNF- α and IL-6. On the antioxidant scale, an increase in SOD, CAT, and GSH levels was observed, accompanied by a decrease in MDA levels. However, the BV treatment led to a significant reduction in the number of eosinophils, monocytes, and neutrophils (p < 0.05). In conclusion, our findings suggested that BV may be utilized to increase the effectiveness of various immunological and hematological parameters.

Synthesis, Antimicrobial Evaluation and Docking Study of Novel 3,5-Disubstituted-2-Isoxazoline and 1,3,5-Trisubstituted-2-Pyrazoline Derivatives.

BACKGROUND: The frequent use of antibacterial agents leads to antimicrobial resistance, which is one of the biggest threats to global health today. Therefore, the discovery of novel antimicrobial agents is still urgently needed to overcome the severe infections caused by these putative pathogens resistant to currently available drugs. OBJECTIVE: The present work was aimed to synthesize and investigate the preliminary structureactivity relationships (SARs) of isoxazoline and pyrazoline derivatives as antimicrobial agent. METHODS: Target compounds were obtained in a multistep reaction synthesis and the antimicrobial activity was investigated in several species; two-gram negative (Escherichia coli and Pseudomonas aeruginosa), two-gram positive (Staphylococcus aureus and Bacillus subtilis) and one fungi (Candida albicans), using cup-plate agar diffusion method. The most potent compounds were docked into glucosamine-6-phosphate synthase (GlcN-6-P), the molecular target enzyme for antimicrobial agents, using Autodock 4.2 program. RESULTS: Herein, thirteen novel target compounds were synthesized in moderate to good isolated yield. Based on the SARs, two compounds (2c and 5c) were found to be potent antimicrobial agents on all tested targets, recording potency higher than amoxicillin, the standard antimicrobial drug. Compound 2b identified as selective for gram-negative, while compound 7a found to be selective for gram-positive. The hit compounds (2c, 5a, 5c and 5d) were subjected to a docking study on glucosamine-6-phosphate synthase (GlcN-6-P). All hits were found to bind to the orthosteric (active) site of the enzyme, which might represent a competitive mechanism of inhibition. CONCLUSION: The newly synthesized heterocyclic compounds could serve as potent leads for the development of novel antimicrobial agents.

Immunomodulatory effect of curcumin on hepatic cirrhosis in experimental rats.

Cirrhosis is a chronic liver disease. The present work aimed to evaluate the regulatory immune effect of curcumin in hepatic cirrhosis induced by carbon tetrachloride (CCl4) injections in experimental rats' model. Chronic liver fibrosis was induced in experiment animals by recurrent injections of CCl4 for more than 5 weeks. They were divided into five groups: first group was injected with normal saline, second group with CCl4, third, fourth, and fifth groups were injected with CCl4 (intraperitoneal injection) at dose 3 ml/kg, two times weekly for 6 weeks supplemented with the administration of curcumin with concentrations 250, 200, and 150 mg/kg. Immune response was analyzed to different treatments. Interleukin 10 (IL-10), pro-inflammatory cytokines TNF-α, TGF-1ß, and liver histopathological examinations were conducted. The results showed that estimations of IL-10 concentrations were significantly increased in curcumin groups compared with CCl4 group, whereas TNF-α and TGF-1ß levels were significantly decreased comparing with CCl4 group. The histopathological examinations for liver tissues showed that curcumin treated groups have almost retained the normal structure of liver tissues. In conclusion, curcumin inhibited hepatic fibrosis and liver fibrogenesis with regulation of the immune system mechanism against invader chemical toxicity. PRACTICAL APPLICATIONS: Curcumin is well documented for its medicinal properties, commonly used as a spice. Our work has thus demonstrated its effectiveness as an immunomodulatory agent. Practically, clinical studies have suggested that curcumin displays a diverse and powerful array of pharmacological effects in nearly all of the human body's major organ systems. These are: antidiabetes, anti-inflammatory, anticancer, antiaging, antioxidant, antibacterial infection, hepatoprotective, neurodegenerative, and cardiovascular effects.

Immunomodulatory effect of papaya (Carica papaya) pulp and seed extracts as a potential natural treatment for bacterial stress.

The current study evaluated the immunomodulatory effects of Carica papaya pulp and seeds methanol (MeOH) extracts on mice infected with Listeria monocytogenes. Gas chromatography-mass spectrometry analysis identified 10 active constituents in C. papaya seed MeOH extract and 10 compounds in C. papaya pulp MeOH extract. The experimental animals were divided into negative control (G1) group, positive control (G2) group, pulp extract treated (G3) group, and seed extract treated (G4) group. After infection of animals (G2, G3, and G4), treatments were started for 3 weeks. Estimation of the immunological parameters showed a marked decrease in IgM levels and an increase in IgG levels in the treated groups (G3 and G4) compared with those in G2. The proinflammatory cytokines (IL-10, IL-12, IL-1ß, IL-6, and TGF-ß1) were decreased in the treated groups (G3 and G4) compared with those in G2. Nitric oxide levels were also decreased, and the percentages of phagocytosis increased compared with those of G2. The results demonstrated the immunomodulatory and anti-inflammatory effects of C. papaya pulp and seeds MeOH extracts. PRACTICAL APPLICATIONS: Based on the antioxidant and antibacterial activities exhibited by the pulp and seed MeOH extracts investigated in this study, Carica papaya might be considered as a natural source of phytochemicals that could be utilized in novel foods and pharmaceuticals. Further investigation are needed to identify and purify compounds that might be responsible for the observed effects.

Ameliorative effects of melatonin against solid Ehrlich carcinoma progression in female mice.

The current work estimated the antitumour efficacy of melatonin (MLT) on the growth of Ehrlich ascites carcinoma cells inoculated intramuscularly into the hind limbs of female BALB/c mice and to compare its effects with those of adriamycin (ADR). After solid tumours developed, the animals were divided into the three following groups: the tumour-bearing control, MLT-treated (20 mg/kg body weight) and ADR-treated (10 mg/kg body weight) groups. The results showed a significant reduction in the tumour masses of the treated animals in comparison with those of the control group. There were a significant decrease in the malondialdehyde level and a significant elevation of the glutathione concentration and the superoxide dismutase and catalase activities in the MLT and ADR groups. The current study indicated the increased expression levels of P53, caspase-3 and caspase-9 and the decreased expression levels of the rRNA and Bcl2. The MLT and ADR treatments resulted in histological changes, such as a marked degenerative area, the necrosis of neoplastic cells, the appearance of different forms of apoptotic cells and giant cells with condensed chromatin, and a deeply eosinophilic cytoplasm. The MLT and ADR treatments also significantly decreased the Ki-67 protein and vascular endothelial growth factor (VEGF) expression levels in the tumour masses. In conclusion, similar to ADR-treated tumour-bearing mice, MLT suppressed the growth and proliferation of tumour by inducing apoptosis and by inhibiting tumour vascularization. The current data recommend MLT as a safe natural chemotherapeutic adjuvant to overcome cancer progression after a clinical trial validates these results.