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10 pages, 1066 KB  
Article
Impact of CCD Inhibition on Semi-Quantitative Multiple Allergen Simultaneous Test
by Hyeyoung Lee, Kyungcheol Song, Jiwoo Kim, Jehyun Koo and Jayoung Kim
Diagnostics 2025, 15(22), 2869; https://doi.org/10.3390/diagnostics15222869 - 12 Nov 2025
Abstract
Background/Objectives: Cross-reactive carbohydrate determinants (CCDs) are a well-recognized source of false-positive results in allergen-specific IgE assays, leading to overestimation of polysensitization. This study aimed to evaluate the impact of CCD inhibition on semi-quantitative multiple allergen simultaneous test (MAST) using the AdvanSure™ AlloScreen [...] Read more.
Background/Objectives: Cross-reactive carbohydrate determinants (CCDs) are a well-recognized source of false-positive results in allergen-specific IgE assays, leading to overestimation of polysensitization. This study aimed to evaluate the impact of CCD inhibition on semi-quantitative multiple allergen simultaneous test (MAST) using the AdvanSure™ AlloScreen Max108 Panel (LG Chem, Seoul, Republic of Korea). Methods: We analyzed 65 serum samples positive for anti-CCD IgE (class ≥ 1). A total of 6624 allergen-specific IgE results across foods, pollens, mites, animal epithelia, and fungi were compared before and after CCD-blocker (20 µg) pretreatment. Results: After CCD-blocker pretreatment, a total of 1686 allergen-specific IgE results converted from positive to negative out of 2631 positives before inhibition (overall conversion rate 64.1%). The reversion to negative rate declined progressively with increasing MAST class (p < 0.0001 for trend). By allergen group, CCD-blocker pretreatment reduced IgE positivity from 28.2% to 8.1% in foods, from 70.1% to 23.3% in pollens, and from 41.0% to 29.2% in mites (all p < 0.001), whereas animal epithelia and fungi exhibited minimal or no significant inhibition. Notably, while CCD antigens themselves exhibited class-dependent conversion rates, non-CCD allergens did not show significant differences by CCD class. In venom allergens, honey bee and yellow jacket IgE levels decreased significantly, with resolution of double-positivity in 94.1% of cases. In the dose–response analysis, increasing the CCD-blocker concentration from 20 µg to 40 µg yielded additional inhibition in selected pollens and foods, while most other allergens showed minimal incremental change. Conclusions: CCD inhibition markedly improves the specificity of MAST by reducing false-positive results, particularly in food and pollen allergens. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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13 pages, 1776 KB  
Article
Development of a Highly Specific Immunoassay for Residual Venom Detection of the Toxic Jellyfish Nemopilema nomurai
by Yi Wang, Yinuo Liu, Xiaochuan Hou, Ying Ge, Xiao Peng, Fengling Yang, Liang Xiao, Juan Höfer, Fei Wang and Jingbo Chen
Toxics 2025, 13(10), 881; https://doi.org/10.3390/toxics13100881 - 16 Oct 2025
Viewed by 347
Abstract
Accurate detection of residual jellyfish venom is crucial for species identification and clinical management post-envenomation. We developed a highly specific immunoassay for Nemopilema nomurai venom using polyclonal antibodies (titer: 1:256,000). The established i-ELISA exhibited linear detection (0–20 ng/mL) with low variability (intra-plate CV: [...] Read more.
Accurate detection of residual jellyfish venom is crucial for species identification and clinical management post-envenomation. We developed a highly specific immunoassay for Nemopilema nomurai venom using polyclonal antibodies (titer: 1:256,000). The established i-ELISA exhibited linear detection (0–20 ng/mL) with low variability (intra-plate CV: 0.77–2.78%; inter-plate CV: 2.25–5.17%). The kit demonstrated remarkable thermal stability (<15% signal decay after 6 days at 37 °C; detectable positivity through Day 9), suggesting >1-year shelf life at 4 °C. It showed significantly higher sensitivity for N. nomurai venom than venoms from Rhopilema esculentum, Chrysaora quinquecirrha, Cyanea melanaster, scorpions, or bees (p < 0.01). Validation in murine/human skin envenomation models and serum from systemically intoxicated mice confirmed the reproducibility and stability of residual toxins. This study developed a highly sensitive, specific, reproducible, and stable i-ELISA for Nemopilema nomurai venom, providing a methodological basis for creating diagnostic kits for marine envenomation. Full article
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17 pages, 1229 KB  
Article
Pro-Apoptotic and Cytotoxic Effects of Melittin on HL-60 Acute Promyelocytic Leukemia Cells: Implications for Retinoid-Independent Therapy
by Maksymilian Stela, Michał Ceremuga, Natalia Cichon, Tomasz Poplawski, Marcin Podogrocki, Leslaw Gorniak and Michał Bijak
Molecules 2025, 30(20), 4093; https://doi.org/10.3390/molecules30204093 - 15 Oct 2025
Viewed by 524
Abstract
Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia driven by the PML/RARα fusion protein. Standard treatment with all-trans retinoic acid (ATRA) combined with chemotherapy is effective, but resistance and adverse effects remain significant challenges. Melittin, the primary peptide component [...] Read more.
Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia driven by the PML/RARα fusion protein. Standard treatment with all-trans retinoic acid (ATRA) combined with chemotherapy is effective, but resistance and adverse effects remain significant challenges. Melittin, the primary peptide component of bee venom, has demonstrated potent anticancer activity across multiple leukemia subtypes through mitochondrial-dependent mechanisms. Building upon this established evidence, we investigated melittin’s therapeutic potential in APL to address the specific clinical challenge of ATRA resistance. Methods: The cytotoxic and pro-apoptotic effects of melittin were studied on the human APL cell line HL-60. Cell viability was assessed using MTT and trypan blue assays. Mitochondrial membrane potential (MMP) was measured with JC-1 staining. Apoptosis was quantified using Annexin V/propidium iodide flow cytometry, caspase-3/7 activity assays, and real-time PCR analysis of apoptosis-related genes (BCL-2, BAX, APAF-1, CASP-3, CASP-8, CASP-9). Results: Melittin reduced HL-60 cell viability in a dose- and time-dependent manner, with significant decreases after 24 and 48 h. MMP analysis revealed mitochondrial depolarization, and Annexin V staining confirmed the induction of apoptosis. Caspase-3/7 activity increased markedly, supporting activation of the intrinsic apoptotic pathway. Gene expression profiling revealed downregulation of the anti-apoptotic BCL-2 and upregulation of the pro-apoptotic BAX, APAF1, and CASP3. At the same time, CASP8 and CASP9 showed no significant changes, suggesting a predominant involvement of the intrinsic pathway. Conclusions: These findings confirm and extend established evidence by demonstrating that melittin’s mitochondrial apoptotic mechanism is consistently active in promyelocytic HL-60 model (PML/RARα-negative). This retinoid-independent mechanism suggests potential therapeutic utility for ATRA-resistant cases or as a complementary strategy in APL treatment. However, selectivity validation in non-cancerous hematopoietic cells represents an important future research priority. Full article
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67 pages, 2023 KB  
Review
Therapeutic Bioactivity Exerted by the Apis mellifera Bee Venom and Its Major Protein Melittin: A Scoping Review
by Perihan Mutlu Erdoğan, Funda Bilgili-Tetikoğlu, Selcen Çelik-Uzuner, Oktay Yıldız, Sevgi Kolayli and Dimitris Mossialos
Molecules 2025, 30(19), 4003; https://doi.org/10.3390/molecules30194003 - 7 Oct 2025
Viewed by 2198
Abstract
Honey bee (Apis mellifera) products have been extensively utilized in traditional medicine. Bee venom (BV) is one of the major bee products with a high concentration of the small peptide melittin (MEL) and exerts bioactivity ranging from anti-microbial to anti-inflammatory and [...] Read more.
Honey bee (Apis mellifera) products have been extensively utilized in traditional medicine. Bee venom (BV) is one of the major bee products with a high concentration of the small peptide melittin (MEL) and exerts bioactivity ranging from anti-microbial to anti-inflammatory and anti-cancer. This scoping review aims to sum up research articles on the bioactivity exerted by BV and MEL published in PubMed and Scopus from 2010 onwards. PRISMA guidelines were implemented to analyze the relevant literature; we ended up with 425 research articles. Bioactivity of BV and MEL was grouped as (i) anti-inflammatory (85), (ii) immunomodulatory (37), (iii) anti-microbial (179), (iv) anti-cancer (170), and (v) anti-oxidant (32). Although there is a significant body of research on the anti-cancer and anti-microbial activity of BV and MEL, their anti-oxidant, anti-inflammatory and immunomodulatory properties have received comparatively less attention. Many studies on the immunomodulatory effects of BV or MEL have focused on cancer. However, the effects on Parkinson’s and Alzheimer’s disease have not been extensively studied regarding the anti-inflammatory effects. Given the critical role of the immune system and inflammatory response in cancer, neurodegenerative diseases, senescence and against infections, it is paramount to further explore the immunomodulatory and anti-inflammatory potential of BV and MEL. Full article
(This article belongs to the Special Issue Bee Products: Recent Progress in Health Benefits Studies, 2nd Edition)
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17 pages, 1022 KB  
Article
Bee Venom Proteins Enhance Proton Absorption by Membranes Composed of Phospholipids of the Myelin Sheath and Endoplasmic Reticulum: Pharmacological Relevance
by Zhuoyan Zeng, Mingsi Wei, Shuhao Zhang, Hanchen Cui, Ruben K. Dagda and Edward S. Gasanoff
Pharmaceuticals 2025, 18(9), 1334; https://doi.org/10.3390/ph18091334 - 5 Sep 2025
Viewed by 659
Abstract
Background/Objectives: Recent evidence challenges the classical chemiosmotic theory, suggesting that proton movement along membrane surfaces—not bulk-phase gradients—drives bioenergetic processes. Proton accumulation on membranes like the myelin sheath and endoplasmic reticulum (ER) may represent a universal mechanism for cellular energy storage. This study [...] Read more.
Background/Objectives: Recent evidence challenges the classical chemiosmotic theory, suggesting that proton movement along membrane surfaces—not bulk-phase gradients—drives bioenergetic processes. Proton accumulation on membranes like the myelin sheath and endoplasmic reticulum (ER) may represent a universal mechanism for cellular energy storage. This study investigates whether phospholipids from these membranes, combined with anionic bee venom proteins, enhance proton absorption, potentially elucidating a novel bioenergetic pathway. Methods: Five phospholipids (phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, phosphatidylcholine) from rat liver were isolated to model myelin/ER membranes. Anionic proteins (pI 5.65–5.80) were purified from bee venom via cation exchange chromatography. Liposomes (with/without proteins) were prepared, and proton absorption was quantified by pH changes in suspensions versus pure water. Statistical significance was assessed via ANOVA and t-tests. Results: All phospholipid liposomes examined in this study absorbed protons under the tested conditions, with phosphatidylethanolamine showing the highest capacity (pH increase: 7.00 → 7.18). Liposomes enriched with anionic proteins exhibited significantly greater proton absorption (e.g., phosphatidylserine + proteins: pH 8.15 vs. 7.15 alone; p < 2.43 × 10−6). Sphingomyelin-protein liposomes absorbed the most protons, suggesting that protein–phospholipid interactions modulate surface proton affinity. Conclusions: Anionic bee venom proteins amplify proton absorption by phospholipid membranes, supporting the hypothesis that lipid–protein complexes act as “proton capacitors”. This mechanism may underpin extramitochondrial energy storage in myelin and ER. Pharmacologically, targeting these interactions could mitigate bioenergetic deficits in aging or disease. Further research should define the structural basis of proton capture by membrane-anchored proteins. Full article
(This article belongs to the Special Issue Recent Research in Therapeutic Potentials of Venoms)
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14 pages, 248 KB  
Editorial
Unveiling the Chemistry and Bioactivity of Bee Products and Their Derivatives
by Ofélia Anjos and Maria da Graça Miguel
Foods 2025, 14(17), 3058; https://doi.org/10.3390/foods14173058 - 29 Aug 2025
Viewed by 953
Abstract
Apiculture, or beekeeping, refers to the cultivation and management of honey bees for honey and byproducts, including the extraction, bottling, and sale of hive products such as honey, propolis, royal jelly, bee venom, bee pollen, bee bread and other fermented bee products [...] [...] Read more.
Apiculture, or beekeeping, refers to the cultivation and management of honey bees for honey and byproducts, including the extraction, bottling, and sale of hive products such as honey, propolis, royal jelly, bee venom, bee pollen, bee bread and other fermented bee products [...] Full article
11 pages, 1309 KB  
Article
The Effect of Bee Venom and Melittin on Glioblastoma Cells in Zebrafish Model
by Agata Małek, Maciej Strzemski and Jacek Kurzepa
Molecules 2025, 30(15), 3306; https://doi.org/10.3390/molecules30153306 - 7 Aug 2025
Cited by 1 | Viewed by 1186
Abstract
Previous in vitro studies have shown the therapeutic potential of bee venom (BV) against different types of glioblastoma cells. Our aim was to evaluate the cytotoxic effect of BV on glioma in the zebrafish model. First, safe concentrations of BV and melittin were [...] Read more.
Previous in vitro studies have shown the therapeutic potential of bee venom (BV) against different types of glioblastoma cells. Our aim was to evaluate the cytotoxic effect of BV on glioma in the zebrafish model. First, safe concentrations of BV and melittin were determined by determining the LD50 for each substance. Two human glioma cell lines, 8MGBA and LN-229, were used in this study. After staining the tested cells for visualization under UV light, they were then implanted into 2-day-old zebrafish embryos. Zebrafish were incubated for 3 days with crude BV and melittin at concentrations of 1.5 and 2.5 µg/mL vs. control group. Tumor growth was assessed with a stereo microscope. We found differential proliferative responses of two human glioma lines in a zebrafish model. The 8MGBA cell line, but not LN-229, showed proliferative potential when implanted into 2-day-old zebrafish embryos. This study showed a dose-dependent cytotoxic effect only for BV against 8MGBA cells. The observed cytotoxic effect is not dependent on the presence of the peptide melittin—the main BV component with the greatest cytotoxic potential. Simultaneously, a slight increase in LN-229 cell proliferation was observed after 3 days of incubation with melittin at a concentration of 2.5 µg/mL. This indicates that any consideration of bee venom as a therapeutic substance must take into account the type of glioblastoma. Full article
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44 pages, 1287 KB  
Review
Antimicrobial Potential of Bee-Derived Products: Insights into Honey, Propolis and Bee Venom
by Agnieszka Grinn-Gofroń, Maciej Kołodziejczak, Rafał Hrynkiewicz, Filip Lewandowski, Dominika Bębnowska, Cezary Adamski and Paulina Niedźwiedzka-Rystwej
Pathogens 2025, 14(8), 780; https://doi.org/10.3390/pathogens14080780 - 6 Aug 2025
Viewed by 3785
Abstract
Bee products, in particular honey, propolis and bee venom, are of growing scientific interest due to their broad spectrum of antimicrobial activity. In the face of increasing antibiotic resistance and the limitations of conventional therapies, natural bee-derived substances offer a promising alternative or [...] Read more.
Bee products, in particular honey, propolis and bee venom, are of growing scientific interest due to their broad spectrum of antimicrobial activity. In the face of increasing antibiotic resistance and the limitations of conventional therapies, natural bee-derived substances offer a promising alternative or support for the treatment of infections. This paper summarizes the current state of knowledge on the chemical composition, biological properties and antimicrobial activity of key bee products. The main mechanisms of action of honey, propolis and bee venom are presented, and their potential applications in the prevention and treatment of bacterial, viral and fungal infections are discussed. Data on their synergy with conventional drugs and prospects for use in medicine and pharmacology are also included. The available findings suggest that, with appropriate standardization and further preclinical and clinical analyses, bee products could become an effective support for the treatment of infections, especially those caused by pathogens resistant to standard therapies. Full article
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16 pages, 1489 KB  
Article
Rapid Change in FcεRI Occupancy on Basophils After Venom Immunotherapy Induction
by Viktoria Puxkandl, Stefan Aigner, Teresa Burner, Angelika Lackner, Sherezade Moñino-Romero, Susanne Kimeswenger, Wolfram Hoetzenecker and Sabine Altrichter
Int. J. Mol. Sci. 2025, 26(15), 7511; https://doi.org/10.3390/ijms26157511 - 4 Aug 2025
Viewed by 712
Abstract
Specific venom immunotherapy (VIT) in patients with hymenoptera venom allergy (HVA) represents a well-studied approach to reduce the severity of a possible anaphylactic reaction. Currently, data on mechanisms of tolerance induction at the cellular level within the first hours of therapy are lacking. [...] Read more.
Specific venom immunotherapy (VIT) in patients with hymenoptera venom allergy (HVA) represents a well-studied approach to reduce the severity of a possible anaphylactic reaction. Currently, data on mechanisms of tolerance induction at the cellular level within the first hours of therapy are lacking. To address this, total and unoccupied high-affinity IgE receptor (FcεRI) numbers per basophil, soluble FcεRI (sFcεRI) and serum tryptase levels were measured before and after the first day of VIT induction in HVA patients. Additionally, basophil activation tests (BATs) were performed at those time points. In the early phase of VIT induction, no significant change in total FcεRI receptor density on basophils was observed, but a significant increase in unoccupied FcεRI was noticeable, predominantly in patients with high total IgE and low baseline unoccupied FcεRI density. No meaningful difference in serum tryptase levels or sFcεRI levels was observed after VIT induction. BATs showed heterogeneous results, often unchanged before and after VIT (in 47% of the cases), sometimes increased (in 40%) and only rarely decreased EC50 sensitivity (in 13%). Changes in the BAT EC50 correlated with FcεRI receptor density changes in basophils. In summary, VIT induction led to an increased ratio of unoccupied-to-total FcεRI without notable tryptase or sFcεRI serum elevation, pointing towards subthreshold cell activation with receptor internalization and recycling. However, the mostly unchanged or even increased basophil sensitivity in EC50 calls for further research to clarify the clinical relevance of these rapid receptor modulations. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Allergen-Specific Immunotherapy)
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29 pages, 2351 KB  
Review
Animal Venoms as Potential Antitumor Agents Against Leukemia and Lymphoma
by Geovanna M. Malachias-Pires, Eloise T. M. Filardi, Marcela Romanazzi, Julia Lopes-de-Oliveira, Isabela C. dos Santos, Guilherme Melo-dos-Santos, Ana Beatriz Rossi, Michele Procópio Machado, Thiago A. da Silva and Manuela B. Pucca
Cancers 2025, 17(14), 2331; https://doi.org/10.3390/cancers17142331 - 14 Jul 2025
Viewed by 1387
Abstract
Leukemias and lymphomas are hematologic malignancies characterized by complex pathophysiological mechanisms and increasing global incidence. Despite advances in chemotherapy, immunotherapy, and targeted therapies, challenges such as drug resistance and relapse persist, necessitating novel therapeutic strategies. This review explores the cytotoxic potential of venoms [...] Read more.
Leukemias and lymphomas are hematologic malignancies characterized by complex pathophysiological mechanisms and increasing global incidence. Despite advances in chemotherapy, immunotherapy, and targeted therapies, challenges such as drug resistance and relapse persist, necessitating novel therapeutic strategies. This review explores the cytotoxic potential of venoms derived from snakes, bees, and scorpions against leukemia and lymphoma cells. Numerous venom-derived components, such as L-amino acid oxidases (LAAOs), phospholipases A2 (PLA2s), and peptides like melittin, demonstrate selective antitumor activity through mechanisms involving oxidative stress, apoptosis induction, cell cycle arrest, and immunomodulation. These molecules exert their effects via mitochondrial pathways, caspase activation, and inhibition of pro-survival signaling cascades such as NF-κB and PI3K/Akt. Despite promising preclinical results, the clinical translation of these bioactive compounds remains limited due to challenges in standardization, delivery, and safety profiling. This review highlights recent advances in venom research, summarizes key molecular targets, and discusses future directions to harness venom-derived molecules as innovative therapies for hematological cancers. Full article
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9 pages, 1664 KB  
Communication
Molecular Diagnosis in Hymenoptera Allergy: Comparison of Euroline DPA-Dx and ImmunoCAP
by Lluís Marquès, Arantza Vega, Federico de la Roca, Carmen Domínguez, Víctor Soriano-Gomis, Teresa Alfaya, Laia Ferré-Ybarz, José-María Vega, Mario Tubella and Berta Ruiz-León
Toxins 2025, 17(6), 310; https://doi.org/10.3390/toxins17060310 - 19 Jun 2025
Viewed by 1025
Abstract
The efficacy of Hymenoptera venom immunotherapy is contingent upon the accurate identification of the insect responsible for the allergic reaction. The techniques used to detect specific IgE suffer from difficulties due to the cross-reactivity between Hymenoptera venoms (false positives), diagnostic ability, and the [...] Read more.
The efficacy of Hymenoptera venom immunotherapy is contingent upon the accurate identification of the insect responsible for the allergic reaction. The techniques used to detect specific IgE suffer from difficulties due to the cross-reactivity between Hymenoptera venoms (false positives), diagnostic ability, and the limited availability of allergenic components (false negatives). In this study, we analyzed the discrepancies in the results obtained with Euroline® DPA-Dx and ImmunoCAP® in the diagnosis of allergic reactions due to Hymenoptera stings in 151 patients. The results (positive/negative) of ImmunoCAP® and Euroline® agreed in 77/151 (50.99%) cases; with 15/151 (9.93%) cases positive for the same insect, and 61/151 (40.4%) cases positive for multiple insects. When the results were used to decide which venom to use for immunotherapy, there was a statistically significant discrepancy for Polistes dominula (21.8% of cases with ImmunoCAP® compared to only 8.4% with Euroline®). The presence of Polistes venom phospholipase (Pol d 1) in Euroline® did not increase its ability to differentiate double sensitization to wasps. ImmunoCAP® and Euroline® exhibited comparable diagnostic performance in bee venom allergy. For vespid venom allergy—particularly involving Polistes species—ImmunoCAP® appeared to show a slight diagnostic advantage, although this finding should be interpreted with caution. Full article
(This article belongs to the Section Animal Venoms)
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31 pages, 7673 KB  
Review
Phospholipase A2—A Significant Bio-Active Molecule in Honeybee (Apis mellifera L.) Venom
by Mara Muntean and Adrian Florea
Molecules 2025, 30(12), 2623; https://doi.org/10.3390/molecules30122623 - 17 Jun 2025
Cited by 1 | Viewed by 2266
Abstract
Phospholipase A2 (PLA2) is a prevalent molecule in the honeybee venom. Its importance is reflected by the number of scientists focused on studying it from various points of view. This review summarises a significant amount of data concerning this fascinating [...] Read more.
Phospholipase A2 (PLA2) is a prevalent molecule in the honeybee venom. Its importance is reflected by the number of scientists focused on studying it from various points of view. This review summarises a significant amount of data concerning this fascinating substance. Firstly, the origin and occurrence of PLA2, with similarities and differences among species or populations of bees are highlighted. Next, its synthesis, post-translational processing and structural features are described, followed by the PLA2 availability. In a larger section, the multiple effects of honeybee venom PLA2 are detailed, starting with the main ability as an enzyme to interact with biological membranes and to hydrolyse the sn-2 ester bond in 1,2-diacyl-sn-3-phosphoglycerides; the docking process, the substrate binding and the catalytic steps are analysed too. Then, the pro-/anti-inflammatory effect and allergenic property, the anticoagulant effect and the involvement of PLA2 in apoptosis are revised. Selected antiviral, antibiotic and antitumoral effects of PLA2, as well as its use in immunotherapy are mentioned as beneficial applications. Additionally, the mechanisms of toxicity of PLA2 are presented in detail. Finally, a number of anti-PLA2 compounds are enumerated. In each section, the features of the honeybee venom molecule are discussed in relation to PLA2s from other species. Full article
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21 pages, 946 KB  
Review
Immunomodulatory and Anti-Inflammatory Properties of Honey and Bee Products
by Bashar Saad
Immuno 2025, 5(2), 19; https://doi.org/10.3390/immuno5020019 - 30 May 2025
Cited by 3 | Viewed by 6453
Abstract
Honey and other bee products, including propolis, royal jelly, and bee pollen, are widely recognized for their medicinal properties. Among their numerous biological activities, their anti-inflammatory and immunomodulatory effects have gained significant attention in recent years. Immune and inflammatory disorders contribute significantly to [...] Read more.
Honey and other bee products, including propolis, royal jelly, and bee pollen, are widely recognized for their medicinal properties. Among their numerous biological activities, their anti-inflammatory and immunomodulatory effects have gained significant attention in recent years. Immune and inflammatory disorders contribute significantly to the development of chronic conditions, including cancer and diabetes. Bee-derived products, along with their bioactive compounds such as polyphenols, have shown promising therapeutic effects in modulating inflammatory mediators. Studies indicate that these products help regulate tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and interleukin-7 (IL-7) levels while reducing reactive oxygen species (ROS) production. Additionally, both in vitro and in vivo research, along with clinical studies, highlight their role in enhancing immune responses by activating B and T lymphocytes. This review explores the molecular mechanisms underlying these properties, emphasizing the role of bioactive compounds such as flavonoids, phenolic acids, and proteins in modulating immune responses and reducing inflammation. Evidence from in vitro, in vivo, and clinical studies suggests that honey and bee products influence cytokine production, regulate immune cell activity, and mitigate oxidative stress, making them potential therapeutic agents for inflammatory and immune-related disorders. To gather relevant information, databases such as Google Scholar, PubMed, and ScienceDirect were searched using various keyword combinations, including immunomodulatory, anti-inflammatory, bee products, honey, propolis, royal jelly, bee venom, and bee pollen. Given their anti-inflammatory, immune-protective, antioxidant, anti-apoptotic, and antimicrobial properties, bee products remain a subject of interest for further clinical evaluation. Full article
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16 pages, 1260 KB  
Review
Clinical Evidence of Bee Venom Acupuncture for Ankle Pain: A Review of Clinical Research
by Soo-Hyun Sung, Hyein Jeong, Jong-Hyun Park, Minjung Park and Gihyun Lee
Toxins 2025, 17(5), 257; https://doi.org/10.3390/toxins17050257 - 21 May 2025
Cited by 1 | Viewed by 2758
Abstract
The prevalence of ankle pain in adults is 9–15%, with up to 45% of sports-related injuries attributed to ankle pain and injuries. If ankle pain is not controlled in a timely manner, it can lead to ankle instability, resulting in further damage, recurrence [...] Read more.
The prevalence of ankle pain in adults is 9–15%, with up to 45% of sports-related injuries attributed to ankle pain and injuries. If ankle pain is not controlled in a timely manner, it can lead to ankle instability, resulting in further damage, recurrence of pain, and secondary injuries. The present study aimed to assess the therapeutic potential and safety profile of bee venom acupuncture (BVA) in the management of ankle pain. Ten electronic databases were searched for articles published up to March 2025. We included clinical studies that utilized BVA for the treatment of ankle pain and studies that included pain- and function-related assessment tools. The safety of bee venom acupuncture (BVA) was assessed by extracting adverse events from the included studies and categorizing them according to the Common Terminology Criteria for Adverse Events (CTCAE). A total of 14 clinical studies were selected, of which 9 were case reports, 2 were case-controlled clinical trials (CCTs), and 3 were randomized controlled trials (RCTs). The conditions causing ankle pain were mostly traumatic (42.9%), followed by inflammatory (21.4%) and neuropathic disorders (14.3%). BVA was applied at concentrations ranging from 0.05 to 0.5 mg/mL, with a per-session volume ranging from 0.04 to 2.5 mL. In most studies, BVA was reported to improve both ankle pain and function simultaneously. Among the 14 studies, four participants reported adverse events following BVA treatment, all of which were classified as grade 1 or grade 2, indicating mild to moderate severity. This review suggests that BVA may be recommended for controlling ankle pain based on clinical evidence. However, the number of high-quality RCTs is limited, and half of the studies did not report side effects, indicating the need for further clinical research to verify its safety and efficacy. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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32 pages, 3654 KB  
Review
Potential of Venom-Derived Compounds for the Development of New Antimicrobial Agents
by Esraa Yasser Rabea, Esraa Dakrory Mahmoud, Nada Khaled Mohamed, Erada Rabea Ansary, Mahmoud Roushdy Alrouby, Rabab Reda Shehata, Youssef Yasser Mokhtar, Prakash Arullampalam, Ahmed M. Hegazy, Ahmed Al-Sabi and Tarek Mohamed Abd El-Aziz
Toxins 2025, 17(5), 238; https://doi.org/10.3390/toxins17050238 - 11 May 2025
Cited by 3 | Viewed by 4854
Abstract
The emergence of antimicrobial resistance is a significant challenge in global healthcare, necessitating innovative techniques to address multidrug-resistant pathogens. Multidrug-resistant pathogens like Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa pose significant public health threats, as they are increasingly resistant to common [...] Read more.
The emergence of antimicrobial resistance is a significant challenge in global healthcare, necessitating innovative techniques to address multidrug-resistant pathogens. Multidrug-resistant pathogens like Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa pose significant public health threats, as they are increasingly resistant to common antibiotics, leading to more severe and difficult-to-treat infections. These pathogens are part of the ESKAPE group, which includes Enterococcus faecium, Staphylococcus aureus, and Enterobacter species. Animal venoms, derived from a wide range of species such as snakes, scorpions, spiders, bees, wasps, and ants, represent a rich source of bioactive peptides. Venoms have been a valuable source for drug discovery, providing unique compounds with therapeutic potential. Venom-derived drugs are known for their increased bioactivity, specificity, and stability compared to synthetic alternatives. These compounds are being investigated for various conditions, including treatments for diabetes, pain relief, cancer, and infections, showcasing their remarkable antimicrobial efficacy. In this review, we provide a comprehensive investigation into the potential of venom-derived compounds for developing new antimicrobial agents, including antibacterial, antifungal, antiviral, and antiparasitic therapeutics. Key venom components, including melittin from bee venom, phospholipase A2 from snake venom, and chlorotoxin from scorpion venom, exhibit potent antimicrobial effects through mechanisms such as membrane disruption, enzymatic inhibition, and immune modulation. We also explore the challenges related to the development and clinical use of venom-derived antimicrobials, including toxicity, stability, and delivery mechanisms. These compounds hold immense promise as transformative tools against resistant pathogens, offering a unique avenue for groundbreaking advancements in antimicrobial research and therapeutic development. Full article
(This article belongs to the Special Issue Animals Venom in Drug Discovery: A Valuable Therapeutic Tool)
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