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In recent years, nanotechnology has revolutionized various sectors, particularly in nanomedicine, where nanomaterials are used for diagnosis, monitoring, control, prevention, and treatment. Among these, silver nanoparticles (AgNPs) stand out due to their remarkable antimicrobial and cytotoxic properties. Traditional chemical synthesis of AgNPs poses significant environmental and health risks. This study introduces a novel, eco‐friendly synthesis method using royal jelly (RJ), a nutrient‐rich secretion from honeybees, to produce AgNPs with potent anticancer effects. Our research provides a detailed investigation into RJ‐mediated AgNPs' modulation of the VEGFa/PI3K/Akt/MMP‐2 pathway in HeLa and A549 cancer cell lines. AgNP characterization was performed by applying UV–Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) in combination with selected area electron diffraction (SAED). Cell signaling system components were determined by ELISA analysis. The cells were subjected to staining with hematoxylin and eosin to visualize the treatment's effects. This study focuses on the green synthesis of AgNPs using RJ and its bioactivity against cancer cells. It provides a detailed characterization of the nanoparticles and examines their effects on cancer cells, specifically HeLa cervical cancer and A549 lung cancer cell lines. Green synthesized AgNPs demonstrate significant cytotoxic effects against HeLa and A549 cancer cell lines. The underlying molecular mechanisms contributing to their anticancer activity were elucidated. Our findings revealed a significant decrease in arginase activity upon exposure to AgNPs, accompanied by reductions in PI3K and phosphorylated and total Akt levels, indicative of pathway inhibition. Additionally, RJAgNP demonstrated a capacity to reduce nitric oxide levels and suppress angiogenesis‐related factors like VEGF and MMP‐2 and inflammation‐related factors like TNF‐α and COX‐2, thus impeding angiogenesis and metastasis. Moreover, our results shed light on the involvement of reactive oxygen intermediates (ROIs) in mediating apoptotic pathways, as evidenced by the increase in malondialdehyde (MDA) concentration and the corresponding decrease in Akt levels, ultimately promoting death in cancer cells. Our study contributes significantly to the field of nanomedicine and cancer therapy by introducing the use of green synthesis AgNPs using RJ and providing in‐depth insights into their molecular mechanisms of anticancer action. Our research findings demonstrate the anticancer potential of RJ‐AgNPs by targeting the VEGFa/PI3K/Akt/MMP‐2 pathway and modulation of ROS/RNS in cancer cells. [ABSTRACT FROM AUTHOR]

Objective(s): In recent years, microplastics (MPs), which are novel environmental contaminants measuring 5 mm in diameter, have garnered considerable attention. However, information regarding substances that can mitigate the dangers of MPs for animals remains extremely limited. Materials and Methods: Ninety days were devoted to the exposure of mature male mice to royal jelly (RJ) and 2 µm virgin polystyrene microplastics (PS-MPs) in this study. Pre-implantation embryo development; the structure of testis tissue; the gonadosomatic index; sperm parameters; RNA damage in germinal cells; the anti-oxidant capacity of the entire testis; and the activity of anti-oxidant enzymes in serum and testicular tissue, including TAC, SOD dismutase, CAT, GSH, and MDA, histomorphometric indices of the testis (tubular differentiation index, spermatogenesis index, and repopulation index), steroidogenic foci, and the quantity of apoptosis were assessed in the testis, respectively, through the measurement of pro-apoptosis (p53, Bax, and Caspase-3) and anti-apoptosis (Bcl-2) factors, as well as Hsp70 mediator. Results: The results indicate that concurrent administration of RJ can confer a protective effect on mice exposed to microplastics by maintaining the structure of mitochondria and enhancement of the anti-oxidant defense system. Furthermore, RJ co-treatment decreased apoptosis and oxidant/anti-oxidant status, enhanced pre-implantation embryo development, and improved sperm characteristics and RNA damage in germ cells. Conclusion: The data confirm that royal jelly could protect the testis structure against polystyrene microplastic-induced testicular injury through anti-oxidant and anti-apoptotic properties. [ABSTRACT FROM AUTHOR]

Lithium is a natural, ubiquitously-occurring alkali metal found in varying amounts in foods like honey. Recently, lithium chloride (LiCl) was described to be effective against varroosis, a parasitic disease leading to loss of honey bee colonies with limited therapy options. However, LiCl treatment is not currently authorized for use in honey bee colonies. Such treatment might result in elevated lithium amounts in honey. To address this, a robust method for quantifying lithium in honey was validated using a microwave-assisted digestion technique combined with Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES), achieving detection levels as low as 0.151 mg/kg. The method was applied to 65 commercially available, randomly chosen honey samples, all of which had lithium levels below the limit of quantitation (LOQ). Furthermore, the method was successfully adapted for use with more complex bee matrices, including royal jelly, bee bread, propolis, and whole bees. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusion Beekeepers face specific occupational health risks due to exposure to bee products and chemicals. Propolis is a notable cause of contact hypersensitivity in beekeepers. Its chemical composition varies by region, complicating allergy investigations. While propolis allergies are documented in Western populations, no studies exist in India.To assess the prevalence and patterns of dermatitis among beekeepers, identify contact sensitisers and evaluate its impact on quality‐of‐life (QoL).An 18‐month community‐based cross‐sectional study was conducted involving 340 beekeepers from the Kashmir Valley in North India. Data collection included personal interviews, dermatological examinations and patch testing using self‐made antigens of propolis, beeswax, royal jelly and standardised Baseline Indian Standard Series. The Dermatology Life Quality Index (DLQI) was used to measure the impact of dermatitis on QoL.Dermatitis prevalence among beekeepers was 17.1%, with the majority presenting with hand eczema. Onset or worsening of dermatitis was reported by 77.6% after working in apiaries. Significant associations were found with duration of beekeeping (p < 0.05) and a history of atopy (p < 0.001). Patch testing revealed 27.5% of beekeepers with positive reactions, primarily to propolis (10% in pet). The mean DLQI score was 3.5, indicating a generally small impact on QoL.Dermatitis was a common occupational condition among beekeepers, strongly associated with the duration of beekeeping and a history of atopy, though its overall impact on QoL was limited. Propolis emerged as a primary sensitiser in the study population. [ABSTRACT FROM AUTHOR]

This study presents a comprehensive multimodal analytical study of an Egyptian ritual Bes-vase, of the 2nd century BCE employing cutting-edge proteomics, metabolomics, genetics techniques, and synchrotron radiation-based Fourier Transformed Infrared microSpectroscopy (SR µ-FTIR) to characterize organic residues of its content. We successfully identified the presence of various functional, bioactive, psychotropic, and medicinal substances, shedding light on the diverse components of a liquid concoction used for ritual practices in Ptolemaic Egypt. Using LC-MS/MS with a new methodological approach, we identified key proteins and metabolites, enabling the identification of botanical sources, confirmed by genetic sequences. Our analyses revealed traces of Peganum harmala, Nimphaea nouchali var. caerulea, and a plant of the Cleome genus, all of which are traditionally proven to have psychotropic and medicinal properties. Additionally, the identification of human fluids suggests their direct involvement in these rituals. Furthermore, metabolomics and SR µ-FTIR analyses also revealed the presence of fermented fruit-based liquid and other ingredients such as honey or royal jelly. The identification of specific chemical compounds, such as alkaloids and flavonoids, provides insight into the psychoactive and therapeutic uses of these in ancient ritual practices. This multidisciplinary study highlights the complexity of ancient cultures and their interactions with psychoactive, medicinal, and bioactive substances. These findings contribute to our understanding of ancient belief systems, cultural practices, and the utilization of natural resources, ultimately enhancing our knowledge of past societies and their connection to the natural world. [ABSTRACT FROM AUTHOR]

The interest in and use of biological materials in crop production is increasing globally at a rapid pace. In many cases, testing methods for conventional chemicals are applied to microbial-based biopesticides because specific microbial test methods are lacking. However, not all methods are easily transferred to microbial-based products. An evaluation was conducted to determine if OECD (Organization for Economic Co-operation and Development) Guidance Document No. 239 on honey bee larval toxicity could be adapted to microbial pesticides. In our study, five microbes, including B. pumilus, B. thuringiensis, B. velezensis, Paenibacillus larvae, and Ascophaera apis were grown on agar media and spotted with either honey bee in vitro larval diet or royal jelly. We observed that the honey bee larval bee diet and royal jelly did not inhibit the fungal honey bee pathogen Ascophaera apis, yet inhibited the growth of bacteria, including a known honey bee larval pathogen. This finding may make the test unreliable for certain biopesticides. The OECD is considering biopesticide-specific testing guidelines, and the EPA has indicated it to update itsbiopesticide bee test guidelines. However, additional research is needed to determine which options may be feasible and provide the best improvements. [ABSTRACT FROM AUTHOR]

Background: Gut microbes are important to the health and fitness of many animals. Many factors have been shown to affect gut microbial communities including diet, lifestyle, and age. Most animals have very complex physiologies, lifestyles, and microbiomes, making it virtually impossible to disentangle what factors have the largest impact on microbiota composition. Honeybees are an excellent model to study host-microbe interactions due to their relatively simple gut microbiota, experimental tractability, and eusociality. Worker honey bees have distinct gut microbiota from their queen mothers despite being close genetic relatives and living in the same environment. Queens and workers differ in numerous ways including development, physiology, pheromone production, diet, and behavior. In the prolonged absence of a queen or Queen Mandibular Pheromones (QMP), some but not all workers will develop ovaries and become "queen-like". Using this inducible developmental change, we aimed to determine if diet and/or reproductive development impacts the gut microbiota of honey bee workers. Results: Microbiota-depleted newly emerged workers were inoculated with a mixture of queen and worker gut homogenates and reared under four conditions varying in diet and pheromone exposure. Three weeks post-emergence, workers were evaluated for ovary development and their gut microbiota communities were characterized. The proportion of workers with developed ovaries was increased in the absence of QMP but also when fed a queen diet (royal jelly). Overall, we found that diet, rather than reproductive development or pheromone exposure, led to more "queen-like" microbiota in workers. However, we revealed that diet alone cannot explain the microbiota composition of workers. Conclusion: The hypothesis that reproductive development explains microbiota differences between queens and workers was rejected. We found evidence that diet is one of the main drivers of differences between the gut microbial community compositions of queens and workers but cannot fully explain the distinct microbiota of queens. Thus, we predict that behavioral and other physiological differences dictate microbiota composition in workers and queens. Our findings not only contribute to our understanding of the factors affecting the honey bee microbiota, which is important for bee health, but also illustrate the versatility and benefits of utilizing honeybees as a model system to study host-microbe interactions. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the gastrointestinal (GI) and reproductive risk associated with chronic usage of celecoxib in male albino rats. METHOD Thirty male albino rats weighing 200-230 g were randomly divided into three equal groups of 10 rats each. In group 1, the control group, rats received no drug. In group 2, rats received celecoxib (50 mg/kg/day, orally) for 30 successive days. In group 3, rats received celecoxib (50 mg/kg/day, orally), and royal jelly (300 mg/kg/day, orally) for 30 successive days. Gastric ulcer scoring and semen analysis were employed to elucidate the celecoxib adverse effects on gastric and testicular tissue functions. RESULTSCelecoxib produced no gastric ulcer in both groups 2 and 3. Celecoxib has no appreciable effect on steroidogenesis (testosterone biosynthesis in Leydig cells of the testis) or spermatogenesis (sperms production from germ cells in the seminiferous tubules of the testis), as indicated by normal sperm count, motility, abnormalities, and normal serum testosterone levels. Royal jelly co-administration did not cause any significant change in serum testosterone level, sperm count, and sperm motility percentage, but caused a significant decline in sperm abnormalities level. CONCLUSIONS Upper GI tolerability and reproductive safety were proved in the chronic use of celecoxib in male albino rats, with ameliorative effects of royal jelly against celecoxib-induced oxidative and apoptotic stress. [ABSTRACT FROM AUTHOR]

Simple Summary: The ontogeny of the queen and worker castes of bees is greatly affected by dietary differences. However, there are few studies that have addressed this issue in the honey bee Apis cerana cerana, a native subspecies of Apis cerana. Through an investigation into the nutritional differences between the diets of queen and worker larvae, as well as the changes in body weight during the growth and development processes of queens and workers, we found that the levels of protein and amino acids in the food of queen larvae are higher than those of worker larvae, and the rate of weight gain in queen larvae is also greater than that of worker larvae. These findings are valuable because the exploration of dietary differences can be helpful when carrying out conservation activities, especially in ex situ artificial rearing practices. The honey bee Apis cerana cerana (A. c. cerana), a subspecies of Apis cerana, is endemic in China and possesses a valuable ecological niche. Understanding the ways to protect this honey bee's populations is crucial, but this topic has been understudied. For the efficient utilization of beekeeping and pollination, there is a need to explore its biology and management practices. In light of this, the current study was carried out to investigate the ontogeny and dietary differences in the queen and worker castes of the A. c. cerana honey bee. This article presents, supplemented by reference images, a detailed description of the life history of A. c. cerana queens and workers. Additionally, this study investigated the nutritional differences between royal jelly (RJ) and worker jelly (WJ) at various larval ages. The contents of the moisture, crude protein, and amino acids in RJ and WJ were determined via freeze drying, Kjeldahl nitrogen determination, and ultra-high performance liquid chromatography. The results highlight significant variations in the moisture content, crude protein concentration, and amino acid concentration between RJ and WJ. The results offer theoretical support for ex situ artificial rearing practices of A. c. cerana. [ABSTRACT FROM AUTHOR]

Queen bee larva (QBL), as a by-product of royal jelly, is a kind of protein-rich edible insect. However, the development and utilization of QBL have been very limited for an extended period, resulting in considerable economic waste. Notably, QBL has substantial potential for anti-aging treatments; however, systematic studies have been scarce. The present study aimed to analyze the effects of freeze-dried QBL powder (QBLP) treatment in a D-galactose (D-gal)-induced-aging mouse and to explore the mechanisms. A behavioral test indicated that QBLP-treated mice had improved cognitive function and memory decline caused by aging compared to untreated aged mice. Furthermore, QBLP treatment improved organ index in aged mice and prevented pathological damage to the brain tissue. Concomitantly, treatment of D-gal-induced-aging mice with QBLP significantly reduced the oxidative damage of serum and increased the skin moisture content of aging mice. Finally, integrated analyses of the gut microbiota and the serum metabolome showed that QBLP supplementation altered the composition of the gut microbiota, enriched biochemical pathways associated with amino acid metabolism, and adjusted serum concentrations of beneficial free amino acids. Overall, QBLP can improve symptoms related to D-gal-induced aging in mice by regulating gut microbiota structure and amino acid metabolism. [ABSTRACT FROM AUTHOR]

Background : Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important. Numerous studies have implicated the gut microbiome in pigs' fat deposition, but research into its suppression remains scarce. The Lulai black pig (LL) is a hybrid breed derived from the Laiwu pig (LW) and the Yorkshire pig, with lower levels of SCF compared to the LW. In this study, we focused on these breeds to identify microbiota that regulate fat deposition. The key questions were: Which microbial populations reduce fat in LL pigs compared to LW pigs, and what is the underlying regulatory mechanism? Results: In this study, we identified four different microbial strains, Eubacterium siraeum, Treponema bryantii, Clostridium sp. CAG:413, and Jeotgalibaca dankookensis, prevalent in both LW and LL pigs. Blood metabolome analysis revealed 49 differential metabolites, including tanshinone IIA and royal jelly acid, known for their anti-adipogenic properties. E. siraeum was strongly correlated with these metabolites, and its genes and metabolites were enriched in pathways linked to fatty acid degradation, glycerophospholipid, and glycerolipid metabolism. In vivo mouse experiments confirmed that E. siraeum metabolites curb weight gain, reduce SCF adipocyte size, increase the number of brown adipocytes, and regulate leptin, IL-6, and insulin secretion. Finally, we found that one important pathway through which E. siraeum inhibits fat deposition is by suppressing the phosphorylation of key proteins in the PI3K/AKT signaling pathway through the reduction of tyrosine. Conclusions: We compared LW and LL pigs using fecal metagenomics, metabolomics, and blood metabolomics, identifying E. siraeum as a strain linked to fat deposition. Oral administration experiments in mice demonstrated that E. siraeum effectively inhibits fat accumulation, primarily through the suppression of the PI3K/AKT signaling pathway, a critical regulator of lipid metabolism. These findings provide a valuable theoretical basis for improving pork quality and offer insights relevant to the study of human obesity and related chronic metabolic diseases. A8f-W15s7ymTLwKonxAA6E Video Abstract [ABSTRACT FROM AUTHOR]

AbstractThe food and pharmaceutical industries have utilized royal jelly, an alternative medicinal food, as a natural pharmaceutical product since ancient times. Royal jelly has a unique remarkable composition containing lipids, proteins, carbohydrates, vitamins, minerals, hormones, and phenolic compounds. The rapidly expanding functional food market has coincided with the increasing consumer demand for royal jelly. Over the past two decades, royal jelly, a rich source of certain bioactive components, has been used by humans as a functional and nutritious food due to recent studies of the effect of royal jelly in underlying pathogenic processes in a variety of animal models. Scientific evidence has accumulated supporting a wide variety of health-promoting effects from the intake of royal jelly that supports cardiovascular health, immune and antioxidant function, wound healing, blood lipid, and glucose control in addition to antibacterial and antihypertensive effects. The main bioactive ingredients are Major Royal Jelly Proteins (MRJPs), essential oils, fatty acids, peptides, and phenolics, which are thought to have a significant role in the development of honeybee queens. The health-endorsing qualities of royal jelly make it a significant functional ingredient in the food, and cosmetic industry. Apisin is one of the main proteins in royal jelly that has antibacterial properties. Other bioactive ingredients of royal jelly that have multifunctional health-promoting properties include defensin-1, royalisin, apisimin, apidaecin, jelleins, royalactin and 10-hydroxy-2-decenoic acid (10HDA) in epigenetic diseases. This review highlights the important role that royal jelly plays as an agent in various fields of medicine, paying special attention to its biological features. Additionally, we discuss royal jelly’s composition as a possible therapeutic for vital natural sources of bioactive substances. [ABSTRACT FROM AUTHOR]

ABSTRACT Royal jelly renowned for its robust nutritional, functional, and biological properties, is a pivotal product derived from honeybees. The purpose of this investigation was to assess the theory that in ovo injection of freeze‐dried royal jelly (FDRJ) solutions at varying concentrations can influence the hatchability, blood properties and hatching characteristics of day‐old chicks. A total of 480 eggs (54.81 ± 0.187 g) were allocated into four experimental groups: negative control (NC), without injection, positive control (PC), administered with regular saline, a low FDRJ dose group (9 mg/egg), and a high FDRJ dose group (18 mg/egg). The in ovo injections were administered on Day 18 of incubation, and the experiment was subsequently continued until the incubation period concluded at 21 days. Results revealed that the lower FDRJ dose (9 mg/egg) significantly improved hatchability percentages compared to other treatments. Conversely, the higher FDRJ dose (18 mg/egg) and control groups (NC and PC) resulted in significantly higher chick yield percentages than the lower FDRJ and PC groups. The NC group showed the supreme yolk sac (YS) percentage, whereas the yolk‐free body mass (YFBM) percentages displayed an inverse trend. Furthermore, the in ovo FDRJ injection did not affect haematological values or the relative organ weight of day‐old chicks. In conclusion, in ovo FDRJ injection demonstrated beneficial effects on hatchability and chick weight, as evidenced by the studied parameters. [ABSTRACT FROM AUTHOR]

Irisin, a novel adipomyokine, has been proposed to be a therapeutic agent against obesity‐related metabolic disease. Royal Jelly (RJ) and tocotrienol‐rich fraction (TRF) are suggested to promote obesity and its related problems through potential mutual mechanistic pathways. This investigation intended to evaluate the glycemic and inflammation‐promoting effects of RJ, TRF, and their combinations to evaluate their synergic effects through irisin action in obese rats induced by a high‐fat diet (HFD) that underwent a calorie restriction diet (CRD). Fifty HFD‐fed obese rats received the following interventions: RJ, TRF, or RJ + TRF in combination with a CRD for eight consecutive weeks. After the investigation, body weight, fasting blood sugar (FBS), irisin, insulin, C‐reactive protein (CRP), interleukin‐6 (IL‐6), interleukin‐1 beta (IL‐1β), leptin, adiponectin, and insulin resistance (IR) were assessed. After 8 weeks of treatment, significant weight reduction was noticed in rats that received RJ and RJ + TRF related to the CRD rats (p <.001), although this reduction was not considerable in TRF‐treated rats. RJ and RJ + TRF supplementation markedly elevated irisin concentrations in CRD rats (p <.05), but TRF did not. Glycemic indices, inflammatory indices including IL‐1β and CRP levels, and leptin concentrations were significantly decreased after RJ, TRF, and their combinations were added to CRD (p <.05). According to the mediational analysis results, irisin mediated the promoting effects of RJ on glycemic hemostasis. Based on the results of this investigation, RJ and TRF are novel nutrients that have the potential to improve obesity‐related disorders. This research suggests that RJ exerts its beneficial glycemic regulatory effects through irisin. [ABSTRACT FROM AUTHOR]

Imidacloprid and other neonicotinoid insecticides severely impact the performance and survival of honey bees and other pollinators. In the present study, we focused on the gene expression profile of newly emerged Apis mellifera queen bees after sublethal imidacloprid treatment during the larval stage. Royal jelly containing 1 ppb imidacloprid was provided to larvae for 3 consecutive days (2–4 days postemergence). Queen larvae treated with imidacloprid showed lower capping and emergence rates (35.5% and 24.22%, respectively) than did control larvae (61.68% and 52.95%, respectively), indicating a high failure rate of queen rearing associated with imidacloprid exposure during the larval stage. The molecular response to imidacloprid treatment was examined next. By comparing the gene expression profiles of imidacloprid‐treated queen larvae and those of control queen larvae using DESeq2, we identified 215 differentially expressed genes, with 105 and 111 up‐ and downregulated genes, respectively. Gene Ontology results indicated that chitin binding– and calcium ion binding–related genes were upregulated, while phototransduction‐ and visual perception–related genes were downregulated. The high mortality rate and altered gene expression profiles suggest that treatment with even 1 ppb imidacloprid can severely impact queen bee survival. Environ Toxicol Chem 2024;43:2232–2242. © 2024 SETAC [ABSTRACT FROM AUTHOR]

The sequencing of the honeybee genome in 2006 was an important technological and logistic achievement experience. But what benefits have flown from the honeybee genome project? What does the annotated genomic assembly mean for the study of behavioural complexity and organismal function in honeybees? Here, I discuss several lines of research that have arisen from this project and highlight the rapidly expanding studies on insect epigenomics, emergent properties of royal jelly, the mechanism of nutritional control of development and the contribution of epigenomic regulation to the evolution of sociality. I also argue that the term 'insect epigenetics' needs to be carefully redefined to reflect the diversity of epigenomic toolkits in insects and the impact of lineage‐specific innovations on organismal outcomes. The honeybee genome project helped pioneer advances in social insect molecular biology, and fuelled breakthrough research into the role of flexible epigenomic control systems in linking genotype to phenotype. [ABSTRACT FROM AUTHOR]

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Abstract Background Gut microbes are important to the health and fitness of many animals. Many factors have been shown to affect gut microbial communities including diet, lifestyle, and age. Most animals have very complex physiologies, lifestyles, and microbiomes, making it virtually impossible to disentangle what factors have the largest impact on microbiota composition. Honeybees are an excellent model to study host-microbe interactions due to their relatively simple gut microbiota, experimental tractability, and eusociality. Worker honey bees have distinct gut microbiota from their queen mothers despite being close genetic relatives and living in the same environment. Queens and workers differ in numerous ways including development, physiology, pheromone production, diet, and behavior. In the prolonged absence of a queen or Queen Mandibular Pheromones (QMP), some but not all workers will develop ovaries and become “queen-like”. Using this inducible developmental change, we aimed to determine if diet and/or reproductive development impacts the gut microbiota of honey bee workers. Results Microbiota-depleted newly emerged workers were inoculated with a mixture of queen and worker gut homogenates and reared under four conditions varying in diet and pheromone exposure. Three weeks post-emergence, workers were evaluated for ovary development and their gut microbiota communities were characterized. The proportion of workers with developed ovaries was increased in the absence of QMP but also when fed a queen diet (royal jelly). Overall, we found that diet, rather than reproductive development or pheromone exposure, led to more “queen-like” microbiota in workers. However, we revealed that diet alone cannot explain the microbiota composition of workers. Conclusion The hypothesis that reproductive development explains microbiota differences between queens and workers was rejected. We found evidence that diet is one of the main drivers of differences between the gut microbial community compositions of queens and workers but cannot fully explain the distinct microbiota of queens. Thus, we predict that behavioral and other physiological differences dictate microbiota composition in workers and queens. Our findings not only contribute to our understanding of the factors affecting the honey bee microbiota, which is important for bee health, but also illustrate the versatility and benefits of utilizing honeybees as a model system to study host-microbe interactions.

Abstract The effect of silver nanoparticles (Ag NPs) obtained in the presence of royal jelly (RJ) on the growth of yeast Candida guilliermondii NP-4, on the total and H+-ATPase activity, as well as lipid peroxidation process and antioxidant enzymes (superoxide dismutase (SOD), catalase) activity was studied. It has been shown that RJ-mediated Ag NPs have a fungicide and fungistatic effects at the concentrations of 5.4 µg mL−1 and 27 µg mL−1, respectively. Under the influence of RJ-mediated Ag NPs, a decrease in total and H+-ATPase activity in yeast homogenates by ~ 90% and ~ 80% was observed, respectively. In yeast mitochondria total and H+-ATPase activity depression was detected by ~ 80% and ~ 90%, respectively. The amount of malondialdehyde in the Ag NPs exposed yeast homogenate increased ~ 60%, the catalase activity increased ~ 70%, and the SOD activity—~ 30%. The obtained data indicate that the use of RJ-mediated Ag NPs have a diverse range of influence on yeast cells. This approach may be important in the field of biomedical research aimed at evaluating the development of oxidative stress in cells. It may also contribute to a more comprehensive understanding of antimicrobial properties of RJ-mediated Ag NPs and help control the proliferation of pathogenic fungi.

Abstract Royal Jelly (RJ) is a natural substance produced by honeybees, serving not only as nutrition for bee brood and queens but also as a functional food due to its health-promoting properties. Despite its well-known broad-spectrum antibacterial activity, the precise molecular mechanism underlying its antibacterial action has remained elusive. In this study, we investigated the impact of RJ on the bacteria model MG1655 at its half-maximal inhibitory concentration, employing LC–MS/MS to analyze proteomic changes. The differentially expressed proteins were found to primarily contribute to the suppression of gene expression processes, specifically transcription and translation, disrupting nutrition and energy metabolism, and inducing oxidative stress. Notably, RJ treatment led to a marked inhibition of superoxide dismutase and catalase activities, resulting in heightened oxidative damage and lipid peroxidation. Furthermore, through a protein–protein interaction network analysis using the STRING database, we identified CRP and IHF as crucial host regulators responsive to RJ. These regulators were found to play a pivotal role in suppressing essential hub genes associated with energy production and antioxidant capabilities. Our findings significantly contribute to the understanding of RJ's antibacterial mechanism, highlighting its potential as a natural alternative to conventional antibiotics. The identification of CRP and IHF as central players highlights the intricate regulatory networks involved in RJ's action, offering new targets for developing innovative antimicrobial strategies.

Background/Objective: This study examined the anti-obesity effect of royal jelly (RJ) in rats fed with a high-fat diet by targeting the major pathways involved in adipogenesis and lipolysis. In addition, it examined whether this effect is AMPK-dependent. Methods: Five groups of adult male albino rats were used (n = 6 each as 1); the control rats were fed with a normal diet (2.9 kcal), and the other groups were as follows: control + RJ (300 mg/kg), HFD (4.75 kcal), HFD + RJ (300 mg/kg), and HFD + RJ (300 mg/kg) + dorsomorphin (an AMPK inhibitor) (0.2 mg/kg). Results: RJ was administered orally to all rats. With no changes in food and energy intake, RJ significantly reduced gains in body weight, fat weight, body mass index (BMI), the Lee index, abdominal circumference (AC), and the adiposity index (AI). It also reduced fasting glucose and insulin levels, HOMA-IR, and the circulatory levels of free fatty acids (FFAs), triglycerides, cholesterol, and LDL-c in the HFD-fed rats. RJ also increased serum glycerol levels and adiponectin levels, but reduced the serum levels of leptin, IL-6, and TNF-α. Moreover, RJ reduced the secretion of IL-6 and TNF-α from isolated WAT. At the tissue level, the HFD + RJ rats exhibited a smaller adipocyte size compared to the HFD rats. At the molecular level, RJ increased the phosphorylation of AMPK, SREBP1, and ACC-1 and increased the mRNA and protein levels of HSL and ATG in the WAT of the HFD rats. In concomitance, RJ increased the mRNA levels of PGC-α1, reduced the protein levels of PPARγ, and repressed the transcriptional activities of PPARγ, SREBP1, and C/EBPαβ in the WAT of these rats. All the aforementioned effects of RJ were prevented by co-treatment with dorsomorphin. Conclusions: RJ exerts a potent anti-obesity effect in rats that is mediated by the AMPk-dependent suppression of WAT adipogenesis and the stimulation of lipolysis. [ABSTRACT FROM AUTHOR]

Background: The incidence of adverse birth outcomes (ABO) in low- and middle-income countries (LIMC) remains significantly elevated. Moringa oleifera (MO), rich nutritional profile, offers to reduce ABO. Therefore, this study aimed to evaluate the impact of MO plus royal jelly capsules on the gestational age and placental weight of newborns in Indonesia. Materials and Methods: A quasi-experimental design setup in the Banggai district, Central Sulawesi Province. The study used a purposive sampling of 80 pregnant women from each sub-district. Moilong District received MRJ, while South Batui District was the Multiple Micronutrient Supplement (MMS) control group. Both groups took one capsule daily for six months. Data analysis using SPSS v28 for Windows, including Chi-square/Fisher's exact test, KolmogorovSmirnov test, Mann-Whitney test, and ANCOVA, with a significance level of p < 0.05. Results: The demographic characteristics in both groups were similar (p > 0.05), except for BMI (p=0.031). Pregnancy outcomes data were also identical (p > 0.05). The Mann-Whitney test did not show a significant difference (p = 0.696) in the gestational age of delivery between the groups. However, there was a significant difference (p < 0.05) in the PW variable within the MRJ group, as shown by the Mann-Whitney test. After adjusting for BMI in PW, the ANCOVA test indicated a significant difference (p = 0.001). Conclusions: The study concludes that MRJ and MMS interventions are effective and safe in preventing ABO in newborns based on gestational age and placental weight. [ABSTRACT FROM AUTHOR]

Introduction: Silver nanoparticles (AgNPs) have widespread commercial application in many products such as home and food products. They lead to various harmful effects. Aim of the Work: The current work aimed to detect the impact of Silver nanoparticles on parotid gland of adult male albino rats and the possible protective role of Royal Jelly. Royal jelly is the hypopharyngeal and mandibular glands' secretion of worker honeybees to feed the young larvae and queen bee. It has been reported to be antioxidant, antihyperglycemic, immunomodulatory and anti-inflammatory agent. Materials and Methods: Thirty rats were equally divided into 3 groups: Control group, treated group which received silver nano particles (AgNPs) by I.P. injection at a dose of 2 mg/kg once daily for 28 days and protective group which received AgNps as the previous dose then received royal jelly orally in gavage in a dose of (1 gm/kg body weight) 3 times a week for 28 days. Tissue malondialdehyde (MDA), tissue superoxide dismutase (SOD) and tissue Amylase were calculated. Specimens of parotid gland were examined by light and electron microscopes. The treated group showed vacuolation of acinar and duct cells, darkly stained nuclei, dilated excretory ducts, congested blood vessels and infiltrating inflammatory cells. Ultrastructurally, there were ill defined organelles, dilated RER, autophagic vacuoles and dark heterochromatic nuclei. Immunohistochemically, there was increased cytoplasmic immunostaining of Bax and increased nuclear and cytoplasmic immunostaining of Ki67 in many acini. Results: These results were estimated morphometrically and statistically. Royal jelly intake showed improving the parotid gland structure and function. Biochemical and histological parameters showed great improvement. Royal Jelly has an ameliorative effect against Silver nanoparticles-induced parotid gland toxicity. Conclusion: Royal jelly has a potent antioxidant activity against silver nanoparticles in parotid gland of adult male albino rats. [ABSTRACT FROM AUTHOR]

This study explores the impact of royal jelly (RJ) on small intestinal epigenomic changes. RJ, produced by honeybees, is known for its effects on metabolic diseases. The hypothesis is that RJ induces epigenomic modifications in small intestinal epithelial cells, affecting gene expression and contributing to metabolic health. Male db/m and db/db mice were used to examine RJ's effects through mRNA sequencing and CUT&Tag methods. This study focused on histone modifications and gene expression changes, with statistical significance set at p < 0.05. RJ administration improved insulin sensitivity and lipid metabolism without affecting body weight. GO and KEGG pathway analyses showed significant enrichment in metabolic processes, cellular components, and molecular functions. RJ altered histone modifications, increasing H3K27me3 and decreasing H3K23Ac in genes associated with the G2M checkpoint. These genes, including Smc2, Mcm3, Ccnd1, Rasal2, Mcm6, and Mad2l1, are linked to cancer progression and metabolic regulation. RJ induces beneficial epigenomic changes in small intestinal epithelial cells, improving metabolic health and reducing cancer-associated gene expression. These findings highlight RJ's potential as a therapeutic agent for metabolic disorders. Further research is needed to fully understand the mechanisms behind these effects and their implications for human health. [ABSTRACT FROM AUTHOR]

Honey bees can be evaluated to study their economic, developmental and immunity aspects. Apis mellifera has important organs such as the hypopharyngeal gland, mandibular gland and brain in their heads. The hypopharyngeal glands and mandibular glands cooperate to produce royal jelly essential in feeding queen honey bees and broods. Moreover, the brain is an organ that regulates the social behaviors of honey bees such as memory and learning. Therefore, this study aimed to detect differential head protein changes in one-day-old and nine-day-old worker honey bees. 153 repeatable protein spots were identified using Melanie software and statistically analyzed. Of the total protein spots, 27 responsive spots were identified using MALDI TOF-TOF mass spectrometry, of which 14 and 8 spots showed up and down regulation, respectively and five spots were expressed just in the head capsules of nine-day-old workers. All identified proteins were divided into 16 different groups involved in various growth-related processes as well as royal jelly augmentation. Nine proteins including KMT5B, TGIF2LX, Protein mono-ADP-ribosyltransferase PARP12, TCL1B4, maph-9, Vimentin-type intermediate filament-associated coiled-coil protein, HSP68, tetratricopeptide repeat domain 36 and POC1B were also identified and introduced for the first time in A. mellifera. This study provides valuable information on proteins involved in honey bee head growth and development as well as increasing royal jelly production. [ABSTRACT FROM AUTHOR]

Royal jelly (RJ) is a yellowish-white substance secreted by the secretory glands of young worker bees to feed the larvae and the queen throughout its life. This study investigates the effect of fermented pollen supplementation on RJ production and cell acceptance rate in Iranian honey bees. The experiment was conducted in Marivan, Iran, for 30 days in the summer of 2020. Experimental treatments include (1) control (sugar syrup); (2) pollen cake (raw pollen, powdered sugar, and honey) + sugar syrup; (3) unfermented pollen supplement + sugar syrup; and (4) fermented pollen + sugar syrup. RJ production and cell acceptance rate were measured and estimated at different time intervals. The collected data were analyzed in a completely randomized design using SAS9.4 software using the GLM procedure. The results showed that different experimental treatments had a significant effect (p ≤ 0.05) on the amount of RJ produced. Among various treatments, the highest RJ production was related to the fourth treatment (12.53 g), and the control treatment (8.07 g) had the lowest production rate. In addition, the highest mean percentage of cell acceptance rate (97.58%) was related to the fermented pollen + sugar syrup treatment. The results showed a positive and high correlation between the two traits of cell acceptance rate and RJ production. In general, a fermented supplementary diet is more efficient than unfermented rations with the same ingredients, therefore recommendable for the apiculture industry. [ABSTRACT FROM AUTHOR]

In this study, Royal Jelly was produced from colonies under chemical treatment of coumaphos (Perizin and Checkmite+) and tau-fluvalinate (Apistan), using artificial plastic queen cells. The contamination level was assessed 42 days after the application. The application of CheckMite + strips during the production led to higher levels of acaricide residues in the final product, in contrast to the residues from Perizin and Apistan. For this reason, the CheckMite + strips were further applied in order to assess the contamination of the product after a long period (292 days after the application). For the specific sampling, natural (center and adjacent) and plastic cells were used. The results showed that the contamination of Royal Jelly produced in plastic queen cells decreased with time; one month after removing the strips, residues were not detectable. On the contrary, the contamination of samples collected from natural queen cells was high, particularly from those adjacent to the strips, where even 292 days after the strips' removal, coumaphos concentration was 2.25 ± 0.50 mg kg−1. The maximum concentration (12.52 ± 2.24 mg kg−1) was detected in natural queen cells. Τo our knowledge, this is the highest contamination that has ever been recorded in a food product. Our results suggest that coumaphos may be transferred from wax to Royal Jelly even in low concentrations. Also, the findings of this research provide data for setting safe intervals between acaricide treatment and Royal Jelly production, raising at the same time awareness about the impact of wax contamination on honey bees' health. [ABSTRACT FROM AUTHOR]

These days, a growing consumer demand and scientific interest can be observed for nutraceuticals of natural origin, including apiculture products. Due to the growing emphasis on environmental protection, extensive research has been conducted on the pesticide and heavy metal contamination of bee products; however, less attention is devoted on other food safety aspects. In our review, scientific information on the less‐researched food safety hazards of honey, bee bread, royal jelly, propolis, and beeswax are summarized. Bee products originating from certain plants may inherently contain phytotoxins, like pyrrolizidine alkaloids, tropane alkaloids, matrine alkaloids, grayanotoxins, gelsemium alkaloids, or tutin. Several case studies evidence that bee products can induce allergic responses to sensitive individuals, varying from mild to severe symptoms, including the potentially lethal anaphylaxis. Exposure to high temperature or long storage may lead to the formation of the potentially toxic 5‐hydroxymethylfurfural. Persistent organic pollutants, radionuclides, and microplastics can potentially be transferred to bee products from contaminated environmental sources. And lastly, inappropriate beekeeping practices can lead to the contamination of beekeeping products with harmful microorganisms and mycotoxins. Our review demonstrates the necessity of applying good beekeeping practices in order to protect honeybees and consumers of their products. An important aim of our work is to identify key knowledge gaps regarding the food safety of apiculture products. [ABSTRACT FROM AUTHOR]

Royal Jelly (RJ) is a natural substance produced by honeybees, serving not only as nutrition for bee brood and queens but also as a functional food due to its health-promoting properties. Despite its well-known broad-spectrum antibacterial activity, the precise molecular mechanism underlying its antibacterial action has remained elusive. In this study, we investigated the impact of RJ on the bacteria model MG1655 at its half-maximal inhibitory concentration, employing LC–MS/MS to analyze proteomic changes. The differentially expressed proteins were found to primarily contribute to the suppression of gene expression processes, specifically transcription and translation, disrupting nutrition and energy metabolism, and inducing oxidative stress. Notably, RJ treatment led to a marked inhibition of superoxide dismutase and catalase activities, resulting in heightened oxidative damage and lipid peroxidation. Furthermore, through a protein–protein interaction network analysis using the STRING database, we identified CRP and IHF as crucial host regulators responsive to RJ. These regulators were found to play a pivotal role in suppressing essential hub genes associated with energy production and antioxidant capabilities. Our findings significantly contribute to the understanding of RJ's antibacterial mechanism, highlighting its potential as a natural alternative to conventional antibiotics. The identification of CRP and IHF as central players highlights the intricate regulatory networks involved in RJ's action, offering new targets for developing innovative antimicrobial strategies. [ABSTRACT FROM AUTHOR]

Bee-derived pharmaceutical products, including propolis (PRO) and royal jelly (ROJ), possess outstanding pharmacological properties. However, their efficiency in counteracting the deleterious influences of cadmium (Cd) in testes and the relevant mechanisms entail further investigations. Therefore, this study sheds light on the therapeutic efficacy of PRO and ROJ against testicular dysfunction and infertility induced by Cd. Toward this end, 30 mature male Wistar albino rats were randomly divided into six groups (5 animals/group), including (I) control, (II) Cd, (III) PRO, (IV) ROJ, (V) PRO + Cd, and (VI) ROJ + Cd groups. Furthermore, antioxidant factors, semen quality, hormonal levels, steroidogenic enzymes, and genotoxicity were assessed. Moreover, histopathological and ultrastructural attributes and offspring rates were investigated. The Cd-treated group revealed marked reductions in reduced glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) with an amplification of lipid peroxidation in testes, indicating disruption of the antioxidant defense system. Furthermore, myeloperoxidase (MPO) activity and DNA damage were significantly heightened, implying inflammation and genotoxicity, respectively. Moreover, steroidogenic enzymes, including 17β-Hydroxy Steroid Dehydrogenase 3 (HSD17b3), 3β-Hydroxy Steroid Dehydrogenase 2 (HSD3b2), 17α-hydroxylase/17,20-lyase (CYP17A1), and steroid 5α-reductase 2 (SRD5A2) were markedly diminished accompanied with disorders in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Besides, spermatozoa quality was reduced, associated with a diminution in the diameter of seminiferous tubules. By contrast, PRO or ROJ significantly protected and/or counteracted the Cd-induced pathophysiological consequences, ameliorating antioxidant and inflammatory biomarkers, steroidogenic enzymes, hormonal levels, and sperm properties, along with lessening DNA impairments. Critically, histological and ultrastructural analyses manifested several anomalies in the testicular tissues of the Cd-administered group, including the Leydig and Sertoli cells and spermatozoa. Conversely, PRO or ROJ sustained testicular tissues' structure, enhancing spermatozoa integrity and productivity. Interestingly, treatment with PRO or ROJ improved fertility indices through offspring rates compared to the Cd-animal group. Our data suggest that PRO is a more effective countermeasure than ROJ against Cd toxicity for securing the delicate testicular microenvironment for spermatogenesis and steroidogenesis. [ABSTRACT FROM AUTHOR]

10-hydroxy-2-decenoic acid (10-HDA), which is a unique bioactive fatty acid of royal jelly synthesized by nurse bees for larvae and adult queen bees, is recognized for its dual utility in medicinal and nutritional applications. Previous research has indicated that 10-HDA exerts antitumor effects on numerous tumor cell lines, including colon cancer cells, A549 human lung cancer cells, and human hepatoma cells. The present study extends this inquiry to lymphoma, specifically evaluating the impact of 10-HDA on the SU-DHL-2 cell line. Our findings revealed dose-dependent suppression of SU-DHL-2 cell survival, with an IC50 of 496.8 μg/mL at a density of 3 × 106 cells/well after 24 h. For normal liver LO2 cells and human fibroblasts (HSFs), the IC50 values were approximately 1000 μg/mL and over 1000 μg/mL, respectively. The results of label-free proteomics revealed 147 upregulated and 347 downregulated differentially expressed proteins that were significantly enriched in the complement and coagulation cascades pathway (adjusted p-value = 0.012), including the differentially expressed proteins prothrombin, plasminogen, plasminogen, carboxypeptidase B2, fibrinogen beta chain, fibrinogen gamma chain, and coagulation factor V. The top three hub proteins, ribosomal protein L5, tumor protein p53, and ribosomal protein L24, were identified via protein–protein interaction (PPI) analysis. This result showed that the complement and coagulation cascade pathways might play a key role in the antitumor process of 10-HDA, suggesting a potential therapeutic avenue for lymphoma treatment. However, the specificity of the effect of 10-HDA on SU-DHL-2 cells warrants further investigation. [ABSTRACT FROM AUTHOR]

This review aims to present current knowledge on the effects of honey bee products on animals based on in vivo studies, focusing on their application in clinical veterinary practice. Honey's best-proven effectiveness is in treating wounds, including those infected with antibiotic-resistant microorganisms, as evidenced in horses, cats, dogs, mice, and rats. Propolis manifested a healing effect in numerous inflammatory and painful conditions in mice, rats, dogs, and pigs and also helped in oncological cases in mice and rats. Bee venom is best known for its effectiveness in treating neuropathy and arthritis, as shown in dogs, mice, and rats. Besides, bee venom improved reproductive performance, immune response, and general health in rabbits, chickens, and pigs. Pollen was effective in stimulating growth and improving intestinal microflora in chickens. Royal jelly might be used in the management of animal reproduction due to its efficiency in improving fertility, as shown in rats, rabbits, and mice. Drone larvae are primarily valued for their androgenic effects and stimulation of reproductive function, as evidenced in sheep, chickens, pigs, and rats. Further research is warranted to determine the dose and method of application of honey bee products in animals. [ABSTRACT FROM AUTHOR]

Bee products, abundant in bioactive ingredients, have been utilized in both traditional and contemporary medicine. Their antioxidant, antimicrobial, and anti-inflammatory properties make them valuable for food, preservation, and cosmetics applications. Honeybees are a vast reservoir of potentially beneficial products such as honey, bee pollen, bee bread, beeswax, bee venom, and royal jelly. These products are rich in metabolites vital to human health, including proteins, amino acids, peptides, enzymes, sugars, vitamins, polyphenols, flavonoids, and minerals. The advancement of nanotechnology has led to a continuous search for new natural sources that can facilitate the easy, low-cost, and eco-friendly synthesis of nanomaterials. Nanoparticles (NPs) are actively synthesized using honeybee products, which serve dual purposes in preventive and interceptive treatment strategies due to their richness in essential metabolites. This review aims to highlight the potential role of bee products in this line and their applications as catalysts and food preservatives and to point out their anticancer, antibacterial, antifungal, and antioxidant underlying impacts. The research used several online databases, namely Google Scholar, Science Direct, and Sci Finder. The overall findings suggest that these bee-derived substances exhibit remarkable properties, making them promising candidates for the economical and eco-friendly production of NPs. [ABSTRACT FROM AUTHOR]

Simple Summary: Interest in beekeeping has significantly increased in recent years. A basic understanding of the nutritional and physiological requirements of honeybees is of great interest to improve their welfare and honey yields. The unique anatomic features of the gastrointestinal tract of bees, which enable bees to make optimal use of their food resources, are extensively described in this review. Nectar, pollen, and resins are raw materials for the synthesis of honey, beeswax, propolis, and royal jelly by the honeybee. All of these products are used for nutrition or as food supplements for animals. In the context of these products, the legal requirements for the use of apiculture by-products in animal nutrition are highlighted. Honeybees are some of the smallest farmed animals, and apiculture by-products, e.g., honey, beeswax, propolis, royal jelly, and pollen contribute to animal nutrition. For the effective production of these by-products, the optimal development and nutrient supply of the honeybee is required. Beginning with the development of the mouth and anal pores on the second day of embryonic development, the digestive tract differentiates into the mouth and fore-, mid-, and hindgut during the pupal stage. The various glands within the oral cavity are particularly important, secreting enzymes and substances that are crucial for digestion and hive nutrition, e.g., invertase and royal jelly. Honeybees rely on a specialized caste system, with worker bees collecting nectar, pollen, water, and resin for the nutrition of the entire hive. Macronutrients, including proteins, carbohydrates, and lipids, obtained primarily from pollen and nectar, are essential for the growth and development of larvae and the overall health of the colony. Inadequate nutrient intake can lead to detrimental effects on larval development, prompting cannibalism within the hive. Apiculture by-products possess unique nutritional and therapeutic properties, leading to a growing interest in the use of honey, beeswax, propolis, and pollen as a feed additive. In recent years, the use of apicultural by-products in animal nutrition has been primarily limited to in vivo studies, which have demonstrated various positive impacts on the performance of farm animals. Honey, beeswax, propolis, royal jelly, and pollen are listed feed stuffs according to Regulation (EC) No. 68/2013. However, for animal nutrition there is not any specific legal definition for these products and no legal requirements regarding their ingredients as given for honey or beeswax in European food law. [ABSTRACT FROM AUTHOR]

Simple Summary: One of the major threats to the health status of honey bee colonies is presented by honey bee-associated viruses. Therefore, the detection and identification of viruses in bee colonies is an important step in the fight against them. In this study, we used a novel and non-invasive approach—molecular analysis of environmental RNA as a tool for detection of six of the most widespread viruses in honey bee colonies in bee products (pollen, bee bread, and royal jelly) from different regions in Bulgaria. The obtained results showed successful detection and identification of the Deformed wing virus, the Acute bee paralysis virus, the Black queen cell virus, and the Israeli acute paralysis virus in all the investigated bee products. Phylogenetic analysis of the detected Bulgarian isolates was implemented to reveal the phylogenetic relationships with the highly similar worldwide strains available in the GenBank database. Ultimately, honey bee products represent a valuable source of eRNA, which allows the monitoring of virus infections in bee colonies at local, regional, and even national levels. In the last few years, the isolation and amplification of DNA or RNA from the environment (eDNA/eRNA) has proven to be an alternative and non-invasive approach for molecular identification of pathogens and pests in beekeeping. We have recently demonstrated that bee pollen and bee bread represent suitable biological material for the molecular identification of viral RNA. In the present study, we extracted total RNA from different bee products (pollen, n = 25; bee bread, n = 17; and royal jelly, n = 15). All the samples were tested for the presence of six of the most common honey bee-associated viruses—Deformed wing virus (DWV), Acute bee paralysis virus (ABPV), Chronic bee paralysis virus (CBPV), Sacbrood virus (SBV), Kashmir bee virus (KBV), and Black queen cell virus (BQCV)—using a reverse transcription polymerase chain reaction (RT-PCR). We successfully detected six records of DWV (10.5%, 6/57), four of ABPV (7.0%, 4/57), three of Israeli acute paralysis virus (IAPV) (5.3%, 3/57), and two of BQCV (3.5%, 2/57). Using ABPV primers, we also successfully detected the presence of IAPV. The obtained viral sequences were analyzed for phylogenetic relationships with the highly similar sequences (megablast) available in the GenBank database. The Bulgarian DWV isolates revealed a high homology level with strains from Syria and Turkey. Moreover, we successfully detected a DWV strain B for the first time in Bulgaria. In contrast to DWV, the ABPV isolates formed a separate clade in the phylogenetic tree. BQCV was closely grouped with Russian isolates, while Bulgarian IAPV formed its own clade and included a strain from China. In conclusion, the present study demonstrated that eRNA can be successfully used for molecular detection of honey bee-associated viruses in bee products. The method can assist the monitoring of the health status of honey bee colonies at the local, regional, and even national levels. [ABSTRACT FROM AUTHOR]

Apis mellifera, crucial pollinators for both native and cultivated plants, also yield various products such as honey, wax, royal jelly, and propolis, extensively utilized in the food, pharmaceuticals, and cosmetics industries. Nosema ceranae, a prevalent microsporidian worldwide, stands as a significant pathogen for A. mellifera, showing resistance to conventional antibiotics. Consequently, the exploration of novel compounds for N. ceranae control becomes imperative. Dithiocarbimate derivatives emerge as promising antifungal candidates under evaluation for combating various pathogens, particularly those affecting plants. This study assessed the toxicity profile of six dithiocarbimate derivatives on A. mellifera worker survival and N. ceranae pathogen. Among these, four compounds exhibited minimal bee mortality and proceeded to further evaluation against N. ceranae. In vitro assays demonstrated their inhibitory effects on spore germination. Remarkably, the most potent compound suppressed N. ceranae spores by 62% at a concentration of 20 µmol L−1in vivo. Thus, these dithiocarbimate derivatives represent promising new antifungal agents for combatting nosemosis in honey bee populations. [ABSTRACT FROM AUTHOR]

The use of bees and bee products for therapeutic purposes in human and veterinary medicine is called apitherapy. Natural products have been used throughout human history to protect against and treat diseases. In recent years, the emergence of drug resistance and the occurrence of adverse effects associated with the indiscriminate and irregular use of pharmacological agents have prompted humanity to pursue alternative solutions. One of the most significant solutions is the administration of bee products. The use of bee products in apitherapy applications includes honey, bee venom, pollen, propolis, beeswax, royal jelly, perga and apilarnil (bee larvae). In general, apitherapy products with a wide range of indications are widely used in various system diseases and some dermatologic problems and various effects of these products such as antibacterial, antifungal, antiviral, antioxidant, anticarcinogenic, anti-inflammatory, antidiabetic and immunomodulatory effects in vitro and in vivo have been investigated in many different studies. Apitherapy is less common in veterinary practice than in human medicine. Additionally, bee products are employed in the treatment of other animal diseases, including gastrointestinal disorders, otitis, sinusitis, ophthalmic conditions, dermatological disorders, and skin care. Additionally, bee products are employed as food supplements for animals. The most prevalent additive in animal food is bee pollen. It has been demonstrated to promote growth, reduce mortality and prevent morbidity. Apitherapy has gained importance in the field of veterinary medicine in recent years in order to prevent both human health and economic losses, especially in the treatment of animals consumed as food. [ABSTRACT FROM AUTHOR]

Objective(s): Until recently, a conventional chemotherapy regimen for Acute lymphoblastic leukemia (ALL) is considered an efficient therapeutic method in children. However, suboptimal long-term survival rates in adults, disease relapse, and drug-induced toxicities require novel therapeutic agents for ALL treatments. Today, natural products with pharmacological benefits play a significant role in treating different cancers. Among the most valued natural products, honey bees’ royal jelly (RJ) is one of the most appreciated which has revealed anti-tumor activity against different human cancers. This study aimed to evaluate anti-leukemic properties and the molecular mechanisms of RJ cytotoxicity on ALL-derived Nalm-6 cells. Materials and Methods: The metabolic activity was measured by MTT assay. Apoptosis, cell distribution in the cell cycle, and intracellular reactive oxygen species (ROS) level were investigated using flow cytometry analysis. Moreover, quantitative real-time PCR (qRT-PCR) was performed to scrutinize the expression of various regulatory genes. Results: RJ significantly decreased the viability of Nalm-6 cells but had no cytotoxic effect on normal cells. In addition, RJ induced ROS-mediated apoptosis by up-regulating pro-apoptotic genes while decreasing anti-apoptotic gene expression. The results outlined that ROS-dependent up-regulation of FOXO4 and Sirt1 inhibits the cells’ transition to the S phase of the cell cycle through p21 upregulation. The qRT-PCR analysis of autophagy-related gene expression also demonstrated that RJ induced BECN1 mediated autophagy in Naml-6 cells. Conclusion: Taken together, this study showed that RJ can be utilized as a potent natural substance to induce ALL cells’ programmed cell death. However, further studies are required to examine this compound’s pharmaceutical application. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the hepato-renal protective effect of royal jelly (RJ) against dexamethasone (DEX)-induced toxicity in rat models. Methods: Twenty-four male albino Wistar rats (divided equally into three groups) were administered DEX with or without RJ while control group received normal saline. The serum levels of aspartate aminotransferase (AST), alanine aminotransaminase (ALT), creatinine, uric acid, albumin, and hepatic activities of glucose-6-phosphate dehydrogenase (G6PD) and catalase, as well as levels of glutathione (GSH) and total protein, were measured. Body, kidney and liver weights, as well as blood glucose concentrations, were measured, before and after treatment. Results: Dexamethasone (DEX) produced significant hyperglycemia and hyperuricemia and significant increases in concentrations of kidney and liver function biomarkers (p < 0.05). These changes were accompanied by decreased liver levels of GSH, total protein and catalase. These alterations were significantly reversed in DEX-treated rats given RJ, compared to rats receiving only DEX (p < 0.05). Body weights were also significantly augmented in DEX-injected rats given RJ, relative to rats given DEX alone (p < 0.05). Conclusion: Royal jelly significantly reduces DEX-induced renal and hepatic toxicities, which suggests its probable therapeutic significance in inhibiting glucocorticoid-mediated adverse reactions. This phenomenon should be further investigated and the possible mechanism elucidated. [ABSTRACT FROM AUTHOR]

The popularity of royal jelly (RJ) as a functional food has attracted attention from various industries, especially nutraceuticals, due to the increasing demand from health enthusiasts. Sebacic acid, 10‐hydroxy decanoic acid, and trans‐10‐hydroxy‐2‐decanoic acid are the primary medium‐chain fatty acids (MCFAs) within RJ responsible for their health benefits. This review aims to consolidate information on these MCFAs' metabolic relationship and health functionalities in nutraceutical applications. We also investigated the natural characteristics mediated by these MCFAs and their metabolism in organisms. Finally, the production of these MCFAs using conventional (from castor oil) and alternative (from RJ) pathways was also discussed. This review can be a reference for using them as functional ingredients in nutraceutical industries. [ABSTRACT FROM AUTHOR]

Aging, marked by a gradual decline in physiological functions, presents significant global health challenges. While royal jelly (RJ) is known for its biological activities, its anti-aging mechanisms require further investigation. Using a D-galactose (D-gal)-induced aging mouse model, this study applied untargeted serum metabolomics to explore RJ's effects. RJ administration significantly (P

Royal jelly (RJ) is rich in various nutrients, including proteins and amino acids. RJ consumption improves sexual and urinary function in postmenopausal women, possibly owing to its hormone-like effects. Currently, hormone regulation and assisted reproductive technologies are widely used to treat thin endometria; however, high doses of these drugs can add to liver burden. In this study, RJ proteins and fatty acids were isolated, and their therapeutic effects on thin endometria were investigated in vivo and in vitro to verify their hormone-like regulatory effects. The results showed that RJ and its extracts could regulate endometrial receptivity-related factor expression levels in rats with a thin endometrium, accelerate MCF-7 cell apoptosis, and increase estrogen receptor expression in MCF-7 cells wherein. The estrogen-like effects of RJ and the fatty acids may be the main contributors. RJ may be a potential natural hormone replacement therapy.

The major royal jelly protein 2 (mrjp2) gene is one of the molecular markers that can discriminate between Apis cerana Fabricius and A. mellifera Linnaeus. Due to the lack of mrjp2 gene sequences registered in GenBank for Indonesian A. cerana and A. mellifera, DNA characterization and bioinformatics analysis were needed. This research aimed to characterize the exon-intron organization of mrjp2 genes for both Indonesian bee species and analyze the phylogenetic relationship with other mrjp family genes. DNA samples of Apis cerana and A. mellifera, collected from Bogor, were amplified using MF-MR primer at annealing temperatures of 47 oC and 50 oC, respectively. The length of A. cerana and A. mellifera DNA sequences were 579 and 597 bp, respectively. The DNA sequences of both species were comprised of partial exons 1, introns 1, exons 2, introns 2, and partial exon 3. The number of putative amino acids of A. cerana and A. mellifera mrjp2 genes were 111 and 123, respectively. We confirmed that the partial MRJP2 putative amino acids of both honey bees belong to the MRJP family and contained the peptide signal in the 14 first amino acid sites. Nucleotide variation of the mrjp2 gene in A. cerana was higher than A. mellifera. Phylogenetic tree construction showed that A. cerana and A. mellifera form a monophyletic clade with the A. mellifera mrjp7 gene and another mrjp family gene clustered as reported in a previous study.

Introduction: Females of the Northern house mosquito, Culex pipiens, enter an overwintering dormancy, or diapause, in response to short day lengths and low environmental temperatures that is characterized by small egg follicles and high starvation resistance. During diapause, Culex pipiens Major Royal Jelly Protein 1 ortholog (CpMRJP1) is upregulated in females of Cx. pipiens. This protein is highly abundant in royal jelly, a substance produced by honey bees (Apis mellifera), that is fed to future queens throughout larval development and induces the queen phenotype (e.g., high reproductive activity and longer lifespan). However, the role of CpMRJP1 in Cx. pipiens is unknown. Methods: We first conducted a phylogenetic analysis to determine how the sequence of CpMRJP1 compares with other species. We then investigated how supplementing the diets of both diapausing and nondiapausing females of Cx. pipiens with royal jelly affects egg follicle length, fat content, protein content, starvation resistance, and metabolic profile. Results: We found that feeding royal jelly to females reared in long-day, diapause-averting conditions significantly reduced the egg follicle lengths and switched their metabolic profiles to be similar to diapausing females. In contrast, feeding royal jelly to females reared in short-day, diapause-inducing conditions significantly reduced lifespan and switched their metabolic profile to be similar nondiapausing mosquitoes. Moreover, RNAi directed against CpMRJPI significantly increased egg follicle length of short-day reared females, suggesting that these females averted diapause. Discussion: Taken together, our data show that consuming royal jelly reverses several key seasonal phenotypes of Cx. pipiens and that these responses are likely mediated in part by CpMRJP1. [ABSTRACT FROM AUTHOR]

With the aim to obtain controlled-release systems and to preserve the antioxidant, immunomodulatory, and prebiotic activity of the bioactive compounds, microencapsulation of both honeydew honey and royal jelly into biopolymeric microparticles based on rye bran heteropolysaccharides (HPS) was successfully performed. Honeydew honey and royal jelly microcapsules were prepared by spray-drying method and were characterized in terms of morphology and biological properties. Due to the resistance of the obtained encapsulates to the acidic pH in the stomach and digestive enzymes, the microcapsules showed prebiotic properties positively influencing both the growth, retardation of the dying phase, and the pro-adhesive properties of probiotic bacteria, i.e., Bifidobacterium spp. and lactic acid bacteria. Moreover, as a result of fermentation of the microcapsules of bee products in the lumen of the large intestine, an increased synthesis of short-chain fatty acids, i.e., butyric acid, was found on average by 39.2% in relation to the SCFA concentrations obtained as a result of fermentation of native bee products, thus opening new perspectives for the exploitation of honeydew honey and royal jelly loaded microcapsules for nutraceutical applications. [ABSTRACT FROM AUTHOR]

Royal jelly is a substance secreted by the hypopharyngeal and mandibular glands of nurse honey bees, serving as crucial nutritional source for young larvae, queen honey bees, and also valuable product for humans. In this study, the effect of the feed supplements on the nutritional composition and qualities of royal jelly was investigated. Two types of royal jelly samples were acquired: one from honey bees fed with sugar syrup as a feed supplement and the other from honey bees fed with honey. The production, harvesting, and storage of all royal jelly samples followed standard procedures. Parameters for quality assessment and nutritional value, including stable carbon isotopic ratio, moisture content, 10-hydroxy-2-decenoic acid (10-HDA) level, carbohydrate composition, amino acid composition, and mineral contents, were analyzed. The results revealed that despite variability in moisture content and carbohydrate composition, fructose was lower (2.6 and 4.1 g/100 g as is for sugar-fed and honey-fed royal jelly, respectively) and sucrose was higher (7.5 and 2.7 g/100 g as is for sugar-fed and honey-fed royal jelly, respectively) in the sugar-fed group. The stable isotope ratio (−16.4608‰ for sugar-fed and −21.9304‰ for honey-fed royal jelly) clearly distinguished the two groups. 10-HDA, amino acid composition, and total protein levels were not significantly different. Certain minerals, such as potassium, iron, magnesium, manganese, and phosphorus were higher in the honey-fed group. Hierarchical analysis based on moisture, sugar composition, 10-HDA, and stable carbon isotopes categorized the samples into two distinct groups. This study demonstrated that the feed source could affect the nutritional quality of royal jelly. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) represents a prevalent ocular surface disease. The development of effective nutritional management strategies for DED is crucial due to its association with various factors such as inflammation, oxidative stress, deficiencies in polyunsaturated fatty acids (PUFAs), imbalanced PUFA ratios, and vitamin insufficiencies. Extensive research has explored the impact of oral nutritional supplements, varying in composition and dosage, on the symptoms of DED. The main components of these supplements include fish oils (Omega-3 fatty acids), vitamins, trace elements, and phytochemical extracts. Beyond these well-known nutrients, it is necessary to explore whether novel nutrients might contribute to more effective DED management. This review provides a comprehensive update on the therapeutic potential of nutrients and presents new perspectives for combination supplements in DED treatment. [ABSTRACT FROM AUTHOR]

The honey market has adapted to changing consumer preferences for healthy, sustainable produced, local, and high-quality food, which also leads to the development of new flavored honeys. The aim of the paper is to explore honey consumption trends and examine consumer acceptance of new flavored honeys. Consumer study is based on questionnaire survey combined with the evaluation of sensory attributes (color, taste, aroma, consistency, overall acceptance) of selected samples of flavored honeys (cinnamon, raspberry, cocoa and hazelnuts, grape powder, and ginger). The research was conducted in 2023 in Slovakia with a sample of 86 young consumers. Various statistical methods (the Chi-square test of independence, the Friedman test, Nemenyi procedure, extraction method principal component analysis and principal component analysis) were used to identify consumer acceptance and attitudes toward new flavored honeys. Results indicate that the younger generation tends towards occasional honey consumption, averaging up to 3 kg per year. Furthermore, the results showed that nearly 70% of consumers consume flavored honey and prefer honeys with propolis, pollen, royal jelly, ginger, and cinnamon. The motives for consumption are primarily taste and health benefits and key factors influencing the purchase and consumption of flavored honeys include quality and composition. Sensory evaluation highlights positive evaluations for color of honey with raspberry; aroma, taste, and overall acceptance of honey with cinnamon; and taste of honey with cocoa and hazelnuts. The findings underscore a shifting preference among younger consumers towards flavored honeys, indicating a growing market demand driven by both taste preferences and perceived health benefits, potentially reshaping the honey consumption patterns towards new and value-added products. Consumer study offers new insights for scientific research and provide valuable information for honey producers in developing and marketing of new flavored honey. Additionally, it contributes to public health awareness, emphasizing the significance of flavored honey consumption. [ABSTRACT FROM AUTHOR]

Royal jelly (RJ) is a highly nutritious natural product with great potential for use in medicine, cosmetics, and as a health-promoting food. This bee product is a mixture of important compounds, such as proteins, vitamins, lipids, minerals, hormones, neurotransmitters, flavonoids, and polyphenols, that underlie the remarkable biological and therapeutic activities of RJ. Various bioactive molecules like 10-hydroxy-2-decenoic acid (10-HDA), antibacterial protein, apisin, the major royal jelly proteins, and specific peptides such as apisimin, royalisin, royalactin, apidaecin, defensin-1, and jelleins are characteristic ingredients of RJ. RJ shows numerous physiological and pharmacological properties, including vasodilatory, hypotensive, antihypercholesterolaemic, antidiabetic, immunomodulatory, anti-inflammatory, antioxidant, anti-aging, neuroprotective, antimicrobial, estrogenic, anti-allergic, anti-osteoporotic, and anti-tumor effects. Moreover, RJ may reduce menopause symptoms and improve the health of the reproductive system, liver, and kidneys, and promote wound healing. This article provides an overview of the molecular mechanisms underlying the beneficial effects of RJ in various diseases, aging, and aging-related complications, with special emphasis on the bioactive components of RJ and their health-promoting properties. The data presented should be an incentive for future clinical studies that hopefully will advance our knowledge about the therapeutic potential of RJ and facilitate the development of novel RJ-based therapeutic opportunities for improving human health and well-being. [ABSTRACT FROM AUTHOR]