Objectives: Recent studies have demonstrated that disorders of bone metabolism, which is regulated by RANK/RANKL/OPG signaling pathway, are the cause of osteoporosis. The aim of the study was to investigate the distribution of genotypes of the RANK 575C>T and RANKL –643C>T polymorphisms and to analyze their relationship with bone parameters in postmenopausal women. Material and methods: A total of 310 postmenopausal Caucasian women (139 with osteoporosis, 107 with osteopenia, and 64 healthy postmenopausal controls) were included. Bone mineral density (BMD) at the lumbar region of the spine (L2–L4) was measured by dual energy X-ray absorptiometry (DXA). Genetic analysis was performed using the PCR-RFLP method. Results: Analysis of the frequency of genotypes and alleles of the RANK 575C>T and RANKL –643C>T polymorphisms did not show any statistically significant differences between the study groups (osteoporosis and osteopenia) and postmenopausal women with normal t-score value (ns). Notably, a significant association between the RANKL –643C>T polymorphism and body mass, such as BMI values in osteoporotic women (p<0.05), was observed. Conclusions: Our results suggest lack of association between the 575C>T RANK polymorphism and the development of osteoporosis. The –643C>T RANKL polymorphism, through its significant influence on body weight and BMI value, may contribute to the development of osteoporosis in postmenopausal women. Objectives: Recent studies have demonstrated that disorders of bone metabolism, which is regulated by RANK/RANKL/OPG signaling pathway, are the cause of osteoporosis. The aim of the study was to investigate the distribution of genotypes of the RANK 575C>T and RANKL –643C>T polymorphisms and to analyze their relationship with bone parameters in postmenopausal women. Material and methods: A total of 310 postmenopausal Caucasian women (139 with osteoporosis, 107 with osteopenia, and 64 healthy postmenopausal controls) were included. Bone mineral density (BMD) at the lumbar region of the spine (L2–L4) was measured by dual energy X-ray absorptiometry (DXA). Genetic analysis was performed using the PCR-RFLP method. Results: Analysis of the frequency of genotypes and alleles of the RANK 575C>T and RANKL –643C>T polymorphisms did not show any statistically significant differences between the study groups (osteoporosis and osteopenia) and postmenopausal women with normal t-score value (ns). Notably, a significant association between the RANKL –643C>T polymorphism and body mass, such as BMI values in osteoporotic women (p<0.05), was observed. Conclusions: Our results suggest lack of association between the 575C>T RANK polymorphism and the development of osteoporosis. The –643C>T RANKL polymorphism, through its significant influence on body weight and BMI value, may contribute to the development of osteoporosis in postmenopausal women.

Glioblastoma (GBM) is one of the most invasive central nervous system tumors, with rising global incidence. Therapy resistance and poor prognosis highlight the urgent need for new anticancer drugs. Plant alkaloids, a largely unexplored yet promising class of compounds, have previously contributed to oncology treatments. While past reviews provided selective insights, this review aims to collectively compare data from the last decade on (1) plant alkaloid-based anticancer drugs, (2) alkaloid transport across the blood–brain barrier (BBB) in vitro and in vivo, (3) alkaloid mechanisms of action in glioblastoma models (in vitro, in vivo, ex vivo, and in silico), and (4) cytotoxicity and safety profiles. Additionally, innovative drug delivery systems (e.g., nanoparticles and liposomes) are discussed. Focusing on preclinical studies of single plant alkaloids, this review includes 22 botanical families and 28 alkaloids that demonstrated anti-GBM activity. Most alkaloids act in a concentration-dependent manner by (1) reducing glioma cell viability, (2) suppressing proliferation, (3) inhibiting migration and invasion, (4) inducing cell death, (5) downregulating Bcl-2 and key signaling pathways, (6) exhibiting antiangiogenic effects, (7) reducing tumor weight, and (8) improving survival rates. The toxic and adverse effect analysis suggests that alkaloids such as noscapine, lycorine, capsaicin, chelerythrine, caffeine, boldine, and colchicine show favorable therapeutic potential. However, tetrandrine, nitidine, harmine, harmaline, cyclopamine, cocaine, and brucine may pose greater risks than benefits. Piperine’s toxicity and berberine’s poor bioavailability suggest the need for novel drug formulations. Several alkaloids (kukoamine A, cyclovirobuxine D, α-solanine, oxymatrine, rutaecarpine, and evodiamine) require further pharmacological and toxicological evaluation. Overall, while plant alkaloids show promise in glioblastoma therapy, progress in assessing their BBB penetration remains limited. More comprehensive studies integrating glioma research and advanced drug delivery technologies are needed.

Objectives: Cancer is the second most common cause of death, with breast cancer (BC) as the most frequently diagnosed neoplasm among females. The origin of BC is multifactorial and depends on environmental and genetic factors. The disease presents a significant challenge due to its drug resistance and frequent metastasis. Thus, new effective therapies and metastasis prevention are much needed. Rosmarinic acid (RA) is a natural polyphenol which possesses the ability to inhibit BC cell proliferation and demonstrates cytotoxic properties against those cells. In our study, we examined the effect of RA on the expression of ZEB1, MDM2, ABCB1, PTEN and TWIST1 genes in MCF-7 breast cancer cells. Material and methods: MCF-7 cell cultures were treated with 0.2 μM doxorubicin (DOX) and 1.5, 15 or 50 μM of RA. Real-time PCR reaction was performed to analyze gene expression levels. Results: PCR analysis showed a significant increase of the ZEB1 gene expression, which was about 3-fold for DOX 0.2 μM, 9-fold for 0.2 μM DOX + 1.5 μM RA and 0.2 μM DOX + 15 μM RA (p < 0.05), and about 6.5-fold for 0.2 μM DOX + 50 μM RA (p < 0.05). Furthermore, a decrease of the MDM2 gene expression was observed in all of the examined variants and was about 40–75% (p < 0.05). No influence of DOX and RA combined with DOX on the ABCB1, TWIST1 and PTEN genes was found. Conclusions: The results of our study suggest that RA might be used as an adjuvant therapeutic factor in BC treatment. Objectives: Cancer is the second most common cause of death, with breast cancer (BC) as the most frequently diagnosed neoplasm among females. The origin of BC is multifactorial and depends on environmental and genetic factors. The disease presents a significant challenge due to its drug resistance and frequent metastasis. Thus, new effective therapies and metastasis prevention are much needed. Rosmarinic acid (RA) is a natural polyphenol which possesses the ability to inhibit BC cell proliferation and demonstrates cytotoxic properties against those cells. In our study, we examined the effect of RA on the expression of ZEB1, MDM2, ABCB1, PTEN and TWIST1 genes in MCF-7 breast cancer cells. Material and methods: MCF-7 cell cultures were treated with 0.2 μM doxorubicin (DOX) and 1.5, 15 or 50 μM of RA. Real-time PCR reaction was performed to analyze gene expression levels. Results: PCR analysis showed a significant increase of the ZEB1 gene expression, which was about 3-fold for DOX 0.2 μM, 9-fold for 0.2 μM DOX + 1.5 μM RA and 0.2 μM DOX + 15 μM RA (p < 0.05), and about 6.5-fold for 0.2 μM DOX + 50 μM RA (p < 0.05). Furthermore, a decrease of the MDM2 gene expression was observed in all of the examined variants and was about 40–75% (p < 0.05). No influence of DOX and RA combined with DOX on the ABCB1, TWIST1 and PTEN genes was found. Conclusions: The results of our study suggest that RA might be used as an adjuvant therapeutic factor in BC treatment.

Summary Postmenopausal osteoporosis is the most common metabolic bone disease with important genetic factors. We evaluated the frequency of polymorphism 283G/A of the vitamin D₃ VDR gene receptor. The study included 800 women at the postmenopausal (505) and reproductive (295) age. Statistically significant changes, depending on the genotype, were shown. Introduction Postmenopausal osteoporosis is the most common metabolic bone disease of strong genetic origin with population variability determined by the interaction of genetic and environmental factors. Recognition of different genetic variants underlying development of osteoporosis would make it possible to administer individual symptomatic treatment as well as early prophylactics of osteoporosis. Methods The aim of the study was to evaluate the frequency of polymorphism 283G/A of the vitamin D₃ VDR gene receptor and assessment of its relations with the clinical parameters of osseous turnover and degree of postmenopausal osteoporosis. The study included 800 women at the postmenopausal (505) and reproductive (295) age throughout the Wielkopolska region in Poland. The postmenopausal group included women with osteoporosis and osteopenia and the healthy ones. Women at the reproductive age were healthy. Frequency of the tested gene polymorphism was evaluated in the group where bone mineral density (BMD) was marked and in the control group. Results The obtained test results pointed to correlation of polymorphism VDR 283G/A with the BMD scores for the lumbar vertebrae in women with osteopenia and osteoporosis, therefore the ones at risk of fractures. Vitamin D receptor (VDR) polymorphism correlated with reduced BMD values. Conclusions Polymorphism 283G/A of the vitamin D₃ receptor gene has been proved to be the genetic factor of postmenopausal osteoporosis. The polymorphism mentioned above has been proved to be a factor of mineral bone density changes of women.

Background: CERAMENT™|BONE VOID FILLER is an injectable and moldable ceramic bone substitute material intended for bone voids. The material consists of hydroxyapatite and calcium sulfate hemihydrate. The aim of this study is to present the first long-term results following open curettage of benign bone tumors and tumor-like lesions and void filling with this novel injectable and synthetic bone graft. Methods: Thirty three patients were enrolled into the study between June 2013 and October 2014 .Totally, we treated 24 women and 9 men with a median age of 47 years (range: 22-74). All patients suffered from primary musculoskeletal system disorders (enchondroma 63,6%, giant cell tumor 18%, aneurysmal bone cyst 9%, fibrous dysplasia 9%, Gaucher disease 3%). We performed curettage of pathological lesions, then the bone substitute was administered by means of needle to the void. Results: The average follow-up was 13 months (range: 2-13 months, median 10 months). No metastasis or recurrence had been detected. We received significant clinical improvement relating to VAS, MSTS, and oncological results. Conclusions: The results of our study report that CERAMENT can be successfully used as a bone substitute in patients with various bone diseases, as well as benign bone tumors. CERAMENT can provide an effective and long-term solution for reconstructive procedures following curettage of bone tumors and tumor like lesions.