Honey: A Promising Therapeutic Supplement for the Prevention and Management of Osteoporosis and Breast Cancer

Osteoporosis and breast cancer are serious diseases that have become a significant socioeconomic burden. There are biochemical associations between the two disorders in terms of the amended function of estrogen, receptor activator of nuclear factor kappa beta ligand, oxidative stress, inflammation, and lipid accumulation. Honey as a functional food with high antioxidant and anti-inflammatory properties can contribute to the prevention of various diseases. Its health benefits are mainly related to the content of polyphenols. This review aims to summarize the current knowledge from in vitro, animal, and human studies on the use of honey as a potential therapeutic agent for osteoporosis and breast cancer. Preclinical studies have revealed a beneficial impact of honey on both bone health (microstructure, strength, oxidative stress) and breast tissue health (breast cancer cell proliferation and apoptosis, tumor growth rate, and volume). The limited number of clinical trials, especially in osteoporosis, indicates the need for further research to evaluate the potential benefits of honey in the treatment. Clinical studies related to breast cancer have revealed that honey is effective in increasing blood cell counts, interleukin-3 levels, and quality of life. In summary, honey may serve as a prospective therapeutic supplement for bone and breast tissue health

Roles of Gut Microbiome in Bone Homeostasis and Its Relationship with Bone-Related Diseases

The extended microbial genome—the gut microbiome (GM)—plays a significant role in host health and disease. It is able to influence a number of physiological functions. During dysbiosis, GM is associated with the development of various chronic diseases with impaired bone quality. In general, GM is important for bone homeostasis and can affect it via several mechanisms. This review describes the roles of GM in bone homeostasis through influencing the immune and endocrine functions, short-chain fatty acids production, calcium absorption and the gut–brain axis. The relationship between GM composition and several bone-related diseases, specifically osteoporosis, osteoarthritis, rheumatoid arthritis, diabetes mellitus, obesity and bone cancer, is also highlighted and summarized. GM manipulation may become a future adjuvant therapy in the prevention of many chronic diseases. Therefore, the beneficial effects of probiotic therapy to improve the health status of individuals with aforementioned diseases are provided, but further studies are needed to clearly confirm its effectiveness. Recent evidence suggests that GM is responsible for direct and indirect effects on drug efficacy. Accordingly, various GM alterations and interactions related to the treatment of bone-related diseases are mentioned as well

Dose-Dependent Impact of Bee Pollen Supplementation on Macroscopic and Microscopic Structure of Femoral Bone in Rats

Bee pollen has been successfully used as a feed additive with beneficial impacts on productive, reproductive, and immune conditions of animals. However, its effect on bone structure and bone health remains controversial. Therefore, the purpose of our study was to examine the impact of bee pollen supplementation on macroscopic and microscopic structure of a femoral bone using rats as suitable animal models. Male rats (1 month-old) were assigned into three groups: control (C group) that was fed a standard diet without bee pollen and two bee pollen supplemented groups (P1 and P2 groups) that received an experimental diet including 0.5% and 0.75% of bee pollen, respectively, for 3 months. A number of unfavorable effects of 0.75% bee pollen administration on bone weight, cortical bone thickness, calcium content, alkaline phosphatase activity, sizes of primary osteons’ vascular canals, Haversian canals and secondary osteons in the cortical bone have been recorded, whereas these bone parameters were significantly decreased in the P2 group versus the C group. On the contrary, the concentration of 0.5% did not affect any of bone features mentioned above. In conclusion, the impact of bee pollen supplementation on femoral bone structure of rats depends on the dose used

The impact of cadmium exposure on cell parameters, expression of specific genes and mineralization in cultivated human osteoblasts

Cadmium (Cd) is a widespread environmental pollutant which negatively affects bone health. The aim of this study was to investigate the impact of Cd exposure on cell parameters, expression of specific genes and mineralization in cultivated human osteoblasts. Osteoblasts were incubated without (control group) or with CdCl2 at final Cd concentrations of 0.1, 2, 5, 10, and 50 μM for 2, 4, 6 or 14 days. Cell viability, morphological changes, alkaline phosphatase activity, mineralization, and an expression of 10 genes associated with osteoblast-specific pathways, oxidative stress and cell death were determined. Osteoblast viability decreased at the highest Cd concentrations (5, 10 and 50 μM) after 4 days of treatment. Our findings specified the threshold of Cd exposure with morphological alterations to 5 μM Cd following 4 days of cultivation. Morphometric measurements revealed significantly decreased size of Cd-treated osteoblasts when compared to the control. The alkaline phosphatase activity was dose-dependent with a reduction at 5 μM Cd after 2 days. Cd concentration of 5 μM significantly down-regulated the expression of COL1A1, ALPL, BGLAP, and GPX1 genes. On the contrary, BAX and SOD1 genes were over-expressed at 0.1, 2, 5 μM Cd and TNFSF11 gene transcripts showed an increase at 0.1-2 μM Cd. No significant impact of Cd exposure on transcription levels of WNT5A, RUNX2, and CASP1 genes was detected. Cd at 0.1 μM stimulated the mineralization, while the dose of 1 μM Cd had no effect. In conclusion, Cd exposure had adverse impact on human osteoblasts viability, morphology and function. On molecular level, it was associated with bone matrix protein synthesis, bone remodelling, cell death, and response to oxidative stress. The lowest dose of Cd had the stimulatory effect on bone mineralization

Gut Microbiota–MicroRNA Interactions in Intestinal Homeostasis and Cancer Development

Pre-clinical models and clinical studies highlight the significant impact of the host–microbiota relationship on cancer development and treatment, supporting the emerging trend for a microbiota-based approach in clinical oncology. Importantly, the presence of polymorphic microbes is considered one of the hallmarks of cancer. The epigenetic regulation of gene expression by microRNAs affects crucial biological processes, including proliferation, differentiation, metabolism, and cell death. Recent evidence has documented the existence of bidirectional gut microbiota–microRNA interactions that play a critical role in intestinal homeostasis. Importantly, alterations in microRNA-modulated gene expression are known to be associated with inflammatory responses and dysbiosis in gastrointestinal disorders. In this review, we summarize the current findings about miRNA expression in the intestine and focus on specific gut microbiota–miRNA interactions linked to intestinal homeostasis, the immune system, and cancer development. We discuss the potential clinical utility of fecal miRNA profiling as a diagnostic and prognostic tool in colorectal cancer, and demonstrate how the emerging trend of gut microbiota modulation, together with the use of personalized microRNA therapeutics, might bring improvements in outcomes for patients with gastrointestinal cancer in the era of precision medicine

Vitamin D Receptor Gene Polymorphisms Affect Osteoporosis-Related Traits and Response to Antiresorptive Therapy

The present study analyzed the effect of vitamin D receptor (VDR) gene polymorphisms (ApaI, TaqI, BsmI, FokI, and Cdx2) on bone mineral density (BMD), biochemical parameters and bone turnover markers, fracture prevalence, and response to three types of antiresorptive therapy (estrogen-progesterone, raloxifene, and ibandronate) in 356 postmenopausal women from Slovakia. Association analysis revealed a significant effect of BsmI polymorphism on lumbar spine BMD, serum osteocalcin (OC), and β-CrossLaps levels. While ApaI and Cdx2 polymorphisms were associated with OC and alkaline phosphatase, TaqI polymorphism affected all turnover markers. ApaI, TaqI, and BsmI genotypes increased the risk of spinal, radial, or total fractures with odds ratios ranging from 2.03 to 3.17. Each of therapy types evaluated had a beneficial effect on all osteoporosis-related traits; however, the VDR gene affected only ibandronate and raloxifene treatment. ApaI/aa, TaqI/TT, and BsmI/bb genotypes showed a weaker or no response to ibandronate therapy in femoral and spinal BMD. The impact of aforementioned polymorphisms on turnover markers was also genotype dependent. On the contrary, only TaqI and BsmI polymorphisms influenced raloxifene therapy, even only in lumbar spine BMD. These results point to the potential of using the VDR gene in personalized pharmacotherapy of osteoporosis

Adverse changes in cortical and trabecular bone compartments of the femur in rats with adjuvant-induced arthritis after one remodelling cycle

It is widely known that rheumatoid arthritis (RA) is associated with articular bone damage. However, there is still not enough information on whether the inflammatory process can deteriorate bone microstructure outside the joint as well. Furthermore, the impact of RA on the microscopic structure of cortical and trabecular bone, including parameters of bone microarchitecture, strength, and geometry after one remodelling cycle, has not been determined, yet. Therefore, this study investigated possible alterations in both cortical and trabecular bone compartments of the femur in a rat model of adjuvant-induced arthritis (AA) 28 days post disease induction. AA was generally evoked by a single intradermal injection ofsuspension of heat-inactivated Mycobacterium butyricumin incomplete Freund’s adjuvant. We have found that AA resulted in inflammation as evidenced by increased hind paw swelling, decreased levels of circulating albumin, and elevated levels of nitrite/nitrate, interleukin-1β. Detrimental changes in examined bone parameters related to microarchitecture, strength, and geometry were revealed in AA rats. Overall, AA was associated with bone loss, decreased bone mineral density in bothcortical and trabecular bone compartments, as well as reduced mechanical competence, and more intense vascularization in the cortical bone. According to our results, AA-related inflammation caused structural degradation of cortical and trabecular bone quality, as well as mechanical weakness in the femoral diaphysis leading to bone fragility after only one remodelling cycle. The findings focused on the femoral diaphysis, which is located outside the joint, are the first in this field of research

Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation

Hematologic malignancies are a group of neoplastic conditions that can develop from any stage of the hematopoiesis cascade. Small non-coding microRNAs (miRNAs) play a crucial role in the post-transcriptional regulation of gene expression. Mounting evidence highlights the role of miRNAs in malignant hematopoiesis via the regulation of oncogenes and tumor suppressors involved in proliferation, differentiation, and cell death. In this review, we provide current knowledge about dysregulated miRNA expression in the pathogenesis of hematological malignancies. We summarize data about the clinical utility of aberrant miRNA expression profiles in hematologic cancer patients and their associations with diagnosis, prognosis, and the monitoring of treatment response. Moreover, we will discuss the emerging role of miRNAs in hematopoietic stem cell transplantation (HSCT), and severe post-HSCT complications, such as graft-versus-host disease (GvHD). The therapeutical potential of the miRNA-based approach in hemato-oncology will be outlined, including studies with specific antagomiRs, mimetics, and circular RNAs (circRNAs). Since hematologic malignancies represent a full spectrum of disorders with different treatment paradigms and prognoses, the potential use of miRNAs as novel diagnostic and prognostic biomarkers might lead to improvements, resulting in a more accurate diagnosis and better patient outcomes