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Abstract Hg is considered as the most toxic metal in the environment. Sources of Hg in the environment include burning fossil fuels, burning waste, and forest fires. The long residence time of the gaseous form in the atmosphere allows mercury to be transported over long distances. The pelagic tunicate Salpa thompsoni is an important component of the Antarctic environment. Over the past few decades an expansion of this species to the higher latitudes has been noted, mainly due to the ongoing climate change. The study material consisted of samples of S. thompsoni individuals, collected in the waters surrounding Elephant Island (Western Antarctic). Total mercury and five of its fractions were determined. Whole organisms were analyzed as well as internal organs: stomachs, muscle strips, and tunics. Obtained results showed that the highest concentrations of mercury in salps were observed in stomachs. With the Hg fraction results, it can be concluded that the main route of exposure of S. thompsoni to Hg is presumably absorption from the food—filtered organic and non-organic particles. Moreover, the process of transformation of simple soluble forms into organic forms of Hg in stomachs and intestines and its distribution to other tissues was observed.

Introduction Ankylosing spondylitis (AS) is a chronic inflammatory, progressive disease, which leads to deterioration of chest and spine mobility and decrease of physical capacity with abnormal chest movement patterns. We aimed to assess the usefulness of the 4DBODY technology for evaluation of the effectiveness of AS treatment. Material and methods The 4DBODY technology was assessed on single AS patient with axial involvement. The patient was examined twice, before and after 14 days of rehabilitation. Physiotherapeutic and plethysmographic examinations were used, as well as angular measurement of spine curvatures and measurement of chest mobility. Chest activity measured using the 4DBODY system and the quality of movement were visualized. Results There was observed an increase of chest mobility from 18 mm to 27.9 mm (up 55%) in the 4DBODY system measurement. The quality of the chest movement also improved, the required phases of inspiration were synchronized. The angular position of the spine has also changed. The chest expansion improved from 25 mm to 50 mm measured on the level of the fourth intercostal space and from 30 mm to 50 mm at the Th10 level. Inspiratory and expiratory muscle strength increased respectively from 80% to 93% and from 46% to 86% of the predicted values. Total airway resistance (Rtot) – increase from 59% to 67%, whereas functional residual capacity (FRC) and total lung capacity (TLC) did not change significantly. Conclusions The new 4DBODY technology was found to be an effective method of examination and assessment of the effectiveness of rehabilitation of patients with AS.

Rhodiola rosea, a long-lived herbaceous plant from the Crassulaceae group, contains the active compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key regulatory proteins including runt-related transcription factor 2 and osterix. Additionally, salidroside facilitates angiogenesis via the hypoxia-inducible factor 1-alpha and vascular endothelial growth factor pathway, crucial for coupling bone development with vascular support. Its antioxidant properties offer protection against bone loss by reducing oxidative stress and promoting osteogenic differentiation through the nuclear factor erythroid 2-related factor 2 pathway. Salidroside has the capability to counteract the negative effects of glucocorticoids on bone cells and prevents steroid-induced osteonecrosis. Additionally, it exhibits multifaceted anti-inflammatory actions, notably through the inhibition of tumor necrosis factor-alpha and interleukin-6 expression, while enhancing the expression of interleukin-10. This publication presents a comprehensive review of the literature on the impact of salidroside on various aspects of bone tissue metabolism, emphasizing its potential role in the prevention and treatment of osteoporosis and other diseases affecting bone physiology.

Rosavin, a phenylpropanoid in Rhodiola rosea’s rhizome, and an adaptogen, is known for enhancing the body’s response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin’s impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant attention in the neuroscience and oncological community regarding its neuroimmunomodulatory and oncogenic functions. This review of the literature summarizes and updates contemporary knowledge about PGRN, its associated receptors and signalling pathway involvement in GBM pathogenesis, indicating possible cellular and molecular mechanisms with potential diagnostic, prognostic and therapeutic targets in order to yield successful individual therapeutic strategies. After a review of the literature, we found that there are possible PGRN-targeted therapeutic approaches for implementation in GBM treatment algorithms both in preclinical and future clinical studies. Furthermore, PGRN-targeted therapies exerted their highest efficacy in combination with other established chemotherapeutic agents, such as temozolomide. The results of the analysis suggested that the possible implementation of routine determinations of PGRN and its associated receptors in tumour tissue and biofluids could serve as a diagnostic and prognostic biomarker of GBM. Furthermore, promising preclinical applications of PGRN-related findings should be investigated in clinical studies in order to create new diagnostic and therapeutic algorithms for GBM treatment.

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can affect almost all systems and organs of the human body, including those responsible for reproductive function in women. The multisystem inflammatory response in COVID-19 shows many analogies with mast cell activation syndrome (MCAS), and MCAS may be an important component in the course of COVID-19. Of note, the female sex hormones estradiol (E2) and progesterone (P4) significantly influence mast cell (MC) behavior. This review presents the importance of MCs and the mediators from their granules in the female reproductive system, including pregnancy, and discusses the mechanism of potential disorders related to MCAS. Then, the available data on COVID-19 in the context of hormonal disorders, the course of endometriosis, female fertility, and the course of pregnancy were compiled to verify intuitively predicted threats. Surprisingly, although COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in MCAS, the available clinical data do not provide grounds for treating this mechanism as significantly increasing the risk of abnormal female reproductive function, including pregnancy. Further studies in the context of post COVID-19 condition (long COVID), where inflammation and a procoagulative state resemble many aspects of MCAS, are needed.

Objective. Hemophilic arthropathy is characterized by recurrent bleeding episodes in patients with hemophilia leading to irreversible joint degeneration. The involvement of CX3CL1 (fractalkine) and its receptor CX3CR1 was observed in the pathogenesis of numerous arthritis-associated diseases. Taking this into account, we have presented a study investigating the role of the CX3CL1/CX3XR1 axis in the course of hemophilic arthropathy, including the CX3CL1-dependent expression of CD56+, CD68+, and CD31+ cells along with evaluation of articular cartilage and synovial membrane morphology. Methods. The study was carried out using cases (n=20) of end-stage hemophilic arthropathy with a severe type of hemophilia A and control cases (n=20) diagnosed with osteoarthritis. The biofluids including blood serum and synovial fluid were obtained intraoperatively for the evaluation of CX3CL1 using the ELISA test. Tissue specimens including articular cartilage and synovial membrane were similarly collected during surgery and stained immunohistologically using selected antibodies including anti-CX3CR1, anti-CD56, anti-CD68, and anti-CD31. Additionally, the analysis included the assessment of articular cartilage, synovial membrane, and blood vessel morphology. Results. In our study, we have documented increased average concentration of CX3CL1 in the blood serum of the study group (7.16±0.53 ng/ml) compared to the control group (5.85±0.70 ng/ml) without statistically significant difference in synovial fluid concentration at the same time. We have observed an increased macrophage presence with more marked proliferation and fibrosis of the synovial membrane in the study group. Remaining results such as expression of CX3CR1 presence of NK cells and larger surface area of blood vessels within the synovial membrane were noted also without statistical significance. Conclusions. This study has demonstrated collective CX3CL1/CX3CR1 axis involvement in hemophilic arthropathy pathogenesis introducing new interesting diagnostics and a therapeutic target.

Polyunsaturated fatty acids (ω-3 acids, PUFAs) are essential components of cell membranes in all mammals. A multifactorial beneficial influence of ω-3 fatty acids on the health of humans and other mammals has been observed for many years. Therefore, ω-3 fatty acids and their function in the prophylaxis and treatment of various pathologies have been subjected to numerous studies. Regarding the documented therapeutic influence of ω-3 fatty acids on the nervous and immune systems, the aim of this paper is to present the current state of knowledge and the critical assessment of the role of ω-3 fatty acids in the prophylaxis and treatment of spinal cord injury (SCI) in rodent models. The prophylactic properties (pre-SCI) include the stabilization of neuron cell membranes, the reduction of the expression of inflammatory cytokines (IL-1β, TNF-α, IL-6, and KC/GRO/CINC), the improvement of local blood flow, reduced eicosanoid production, activation of protective intracellular transcription pathways (dependent on RXR, PPAR-α, Akt, and CREB), and increased concentration of lipids, glycogen, and oligosaccharides by neurons. On the other hand, the therapeutic properties (post-SCI) include the increased production of endogenous antioxidants such as carnosine and homocarnosine, the maintenance of elevated GSH concentrations at the site of injury, reduced concentrations of oxidative stress marker (MDA), autophagy improvement (via increasing the expression of LC3-II), and p38 MAPK expression reduction in the superficial dorsal horns (limiting the sensation of neuropathic pain). Paradoxically, despite the well-documented protective activity of ω-3 acids in rodents with SCI, the research does not offer an answer to the principal question of the optimal dose and treatment duration. Therefore, it is worth emphasizing the role of multicenter rodent studies with the implementation of standards which initially may even be based on arbitrary criteria. Additionally, basing on available research data, the authors of this paper make a careful attempt at referring some of the conclusions to the human population.

Osteoporosis is a civilization disease which is still challenging for contemporary medicine in terms of treatment and prophylaxis. It results from excessive activation of the osteoclastic cell line and immune cells like macrophages and lymphocytes. Cell-to-cell inflammatory information transfer occurs via factors including cytokines which form a complex network of cell humoral correlation, called cytokine network. Recently conducted studies revealed the participation of CX3CL1 chemokine in the pathogenesis of osteoporosis. CX3CL1 and its receptor CX3CR1 present unique properties among over 50 described chemokines. Apart from its chemotactic activity, CX3CL1 is the only chemokine which may function as an adhesion molecule which facilitates easier penetration of immune system cells through the vascular endothelium to the area of inflammation. The present study, based on world literature review, sums and describes convincing evidences of a significant role of the CX3CL1/CX3CR1 axis in processes leading to bone mineral density (BMD) reduction. The CX3CL1/CX3CR1 axis plays a principal role in osteoclast maturation and binding them with immune cells to the surface of the bone tissue. It promotes the development of inflammation and production of many inflammatory cytokines near the bone surface (i.e., TNF-α, IL-1β, and IL-6). High concentrations of CX3CL1 in serum are directly proportional to increased concentrations of bone turnover and inflammatory factors in human blood serum (TRACP-5b, NTx, IL-1β, and IL-6). Regarding the fact that acting against the CX3CL1/CX3CR1 axis is a potential target of immune treatment in osteoporosis, the number of available papers tackling the topic is certainly insufficient. Therefore, it seems justified to continue research which would precisely determine its role in the metabolism of the bone tissue as one of the most promising targets in osteoporosis therapy.

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.

Chronic non-bacterial osteomyelitis (CNO) has been known for over of 40 years. It is an underrecognized entity due to the low number of described cases and poor propagation awareness of the problem. Chronic non-bacterial osteomyelitis is usually confused with infectious spondylodiscitis or malignant lesions, both primary and metastatic. Failing to consider CNO as one of possible lesions of the spine among an array of differential diagnoses may lead to a prolonged ineffective treatment increasing treatment-related morbidity. In this paper the authors describe these two syndromes, with a possible autoimmune background – chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO syndrome – that include CNO being among the manifestations. The authors present the spinal symptomatology of CNO for both syndromes published so far to help spine clinicians organize the information for better usage in everyday clinical practice.

The transforming growth factor beta (TGF-β) family forms a group of three isoforms, TGF-β1, TGF-β2, and TGF-β3, with their structure formed by interrelated dimeric polypeptide chains. Pleiotropic and redundant functions of the TGF-β family concern control of numerous aspects and effects of cell functions, including proliferation, differentiation, and migration, in all tissues of the human body. Amongst many cytokines and growth factors, the TGF-β family is considered a group playing one of numerous key roles in control of physiological phenomena concerning maintenance of metabolic homeostasis in the bone tissue. By breaking the continuity of bone tissue, a spread-over-time and complex bone healing process is initiated, considered a recapitulation of embryonic intracartilaginous ossification. This process is a cascade of local and systemic phenomena spread over time, involving whole cell lineages and various cytokines and growth factors. Numerous in vivo and in vitro studies in various models analysing cytokines and growth factors’ involvement have shown that TGF-β has a leading role in the fracture healing process. This paper sums up current knowledge on the basis of available literature concerning the role of the TGF-β family in the fracture healing process.

Introduction and objective. Spinal cord injury (SCI), which disrupts motor, sensory and autonomic functions, causes significant changes in the functioning of an individual. It is believed that most of the conditions secondary to SCI, i.e. osteoporosis, spasticity or cardiopulmonary diseases, are associated with immobility. The aim of the study is to assess the adherence to prescriptions of therapeutic exercises (APTE) in patients with SCI after acute phases of rehabilitation. Materials and methods. The criterionfor APTE recognition was the performance at least twice a week for a minimum of 30 minutes of active exercises with resistance, and exercises maintaining the range of movement of the joints The research tools were own questionnaire and the WHOQOL-BREF scale. Results. 46 subjects (63.9%) met the APTE criteria. The most frequent place for performing the exercises was the subject's home with 43 subjects (93.5%) with APTE performed the exercises in their homes. 17 subjects (36.9%) with APTE performed exercises during stays at various rehabilitation centres. The main cause for the lack of APTE was the limited availability of facilities considered necessary by the respondents to adhere to the instructions. In statistical analysis, the level of neurological injury correlated with meeting the APTE criteria. It was discovered that a subjective assessment of the exercise dose correlated with the place where the exercises were performed, but did not correlate with meeting the APTE criteria. Conclusions. The basic place for performing exercises (as instructed in hospital) was the subject's home. Limited access to reimbursed environmental therapy resulted in an increased cost of exercises supervised by commercially-employed physiotherapists. The current gaps in the system of supervision and counselling of subjects post-SCI necessitate changes in the Polish health care system. [ABSTRACT FROM AUTHOR]

Rhodiola rosea , a long-lived herbaceous plant from the Crassulaceae group, contains the active compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key regulatory proteins including runt-related transcription factor 2 and osterix. Additionally, salidroside facilitates angiogenesis via the hypoxia-inducible factor 1-alpha and vascular endothelial growth factor pathway, crucial for coupling bone development with vascular support. Its antioxidant properties offer protection against bone loss by reducing oxidative stress and promoting osteogenic differentiation through the nuclear factor erythroid 2-related factor 2 pathway. Salidroside has the capability to counteract the negative effects of glucocorticoids on bone cells and prevents steroid-induced osteonecrosis. Additionally, it exhibits multifaceted anti-inflammatory actions, notably through the inhibition of tumor necrosis factor-alpha and interleukin-6 expression, while enhancing the expression of interleukin-10. This publication presents a comprehensive review of the literature on the impact of salidroside on various aspects of bone tissue metabolism, emphasizing its potential role in the prevention and treatment of osteoporosis and other diseases affecting bone physiology.

Rosavin, a phenylpropanoid in Rhodiola rosea 's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant attention in the neuroscience and oncological community regarding its neuroimmunomodulatory and oncogenic functions. This review of the literature summarizes and updates contemporary knowledge about PGRN, its associated receptors and signalling pathway involvement in GBM pathogenesis, indicating possible cellular and molecular mechanisms with potential diagnostic, prognostic and therapeutic targets in order to yield successful individual therapeutic strategies. After a review of the literature, we found that there are possible PGRN-targeted therapeutic approaches for implementation in GBM treatment algorithms both in preclinical and future clinical studies. Furthermore, PGRN-targeted therapies exerted their highest efficacy in combination with other established chemotherapeutic agents, such as temozolomide. The results of the analysis suggested that the possible implementation of routine determinations of PGRN and its associated receptors in tumour tissue and biofluids could serve as a diagnostic and prognostic biomarker of GBM. Furthermore, promising preclinical applications of PGRN-related findings should be investigated in clinical studies in order to create new diagnostic and therapeutic algorithms for GBM treatment.

Introduction: Ankylosing spondylitis (AS) is a chronic inflammatory, progressive disease, which leads to deterioration of chest and spine mobility and decrease of physical capacity with abnormal chest movement patterns. We aimed to assess the usefulness of the 4DBODY technology for evaluation of the effectiveness of AS treatment., Material and Methods: The 4DBODY technology was assessed on single AS patient with axial involvement. The patient was examined twice, before and after 14 days of rehabilitation. Physiotherapeutic and plethysmographic examinations were used, as well as angular measurement of spine curvatures and measurement of chest mobility. Chest activity measured using the 4DBODY system and the quality of movement were visualized., Results: There was observed an increase of chest mobility from 18 mm to 27.9 mm (up 55%) in the 4DBODY system measurement. The quality of the chest movement also improved, the required phases of inspiration were synchronized. The angular position of the spine has also changed. The chest expansion improved from 25 mm to 50 mm measured on the level of the fourth intercostal space and from 30 mm to 50 mm at the Th10 level. Inspiratory and expiratory muscle strength increased respectively from 80% to 93% and from 46% to 86% of the predicted values. Total airway resistance (Rtot) - increase from 59% to 67%, whereas functional residual capacity (FRC) and total lung capacity (TLC) did not change significantly., Conclusions: The new 4DBODY technology was found to be an effective method of examination and assessment of the effectiveness of rehabilitation of patients with AS., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can affect almost all systems and organs of the human body, including those responsible for reproductive function in women. The multisystem inflammatory response in COVID-19 shows many analogies with mast cell activation syndrome (MCAS), and MCAS may be an important component in the course of COVID-19. Of note, the female sex hormones estradiol (E 2 ) and progesterone (P4) significantly influence mast cell (MC) behavior. This review presents the importance of MCs and the mediators from their granules in the female reproductive system, including pregnancy, and discusses the mechanism of potential disorders related to MCAS. Then, the available data on COVID-19 in the context of hormonal disorders, the course of endometriosis, female fertility, and the course of pregnancy were compiled to verify intuitively predicted threats. Surprisingly, although COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in MCAS, the available clinical data do not provide grounds for treating this mechanism as significantly increasing the risk of abnormal female reproductive function, including pregnancy. Further studies in the context of post COVID-19 condition (long COVID), where inflammation and a procoagulative state resemble many aspects of MCAS, are needed., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Dariusz Szukiewicz et al.)

Breast cancer constitute a common type of oncological disease with a highlighted mortality rate. In recent years, researchers have introduced progranulin (PGRN) as an novel potential biomarker and associated its function with higher risk factor for development of breast cancer. The present review article collects evidence on the association of PGRN with clinicopathological features and drug resistance in the patients with breast cancer. The results of this study suggested the use of routine determination of PGRN in the clinic as a reliable biomarker for screening people at high risk or as early indication of breast cancer. Targeting PGRN and its associated signaling pathways and receptors, such as sortilin (SORT1), could also cover a novel therapeutic strategy in the breast cancer., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.

Objective: Hemophilic arthropathy is characterized by recurrent bleeding episodes in patients with hemophilia leading to irreversible joint degeneration. The involvement of CX3CL1 (fractalkine) and its receptor CX3CR1 was observed in the pathogenesis of numerous arthritis-associated diseases. Taking this into account, we have presented a study investigating the role of the CX3CL1/CX3XR1 axis in the course of hemophilic arthropathy, including the CX3CL1-dependent expression of CD56 + , CD68 + , and CD31 + cells along with evaluation of articular cartilage and synovial membrane morphology., Methods: The study was carried out using cases ( n = 20) of end-stage hemophilic arthropathy with a severe type of hemophilia A and control cases ( n = 20) diagnosed with osteoarthritis. The biofluids including blood serum and synovial fluid were obtained intraoperatively for the evaluation of CX3CL1 using the ELISA test. Tissue specimens including articular cartilage and synovial membrane were similarly collected during surgery and stained immunohistologically using selected antibodies including anti-CX3CR1, anti-CD56, anti-CD68, and anti-CD31. Additionally, the analysis included the assessment of articular cartilage, synovial membrane, and blood vessel morphology., Results: In our study, we have documented increased average concentration of CX3CL1 in the blood serum of the study group (7.16 ± 0.53 ng/ml) compared to the control group (5.85 ± 0.70 ng/ml) without statistically significant difference in synovial fluid concentration at the same time. We have observed an increased macrophage presence with more marked proliferation and fibrosis of the synovial membrane in the study group. Remaining results such as expression of CX3CR1 presence of NK cells and larger surface area of blood vessels within the synovial membrane were noted also without statistical significance., Conclusions: This study has demonstrated collective CX3CL1/CX3CR1 axis involvement in hemophilic arthropathy pathogenesis introducing new interesting diagnostics and a therapeutic target., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Piotr Wojdasiewicz et al.)

Polyunsaturated fatty acids ( ω -3 acids, PUFAs) are essential components of cell membranes in all mammals. A multifactorial beneficial influence of ω -3 fatty acids on the health of humans and other mammals has been observed for many years. Therefore, ω -3 fatty acids and their function in the prophylaxis and treatment of various pathologies have been subjected to numerous studies. Regarding the documented therapeutic influence of ω -3 fatty acids on the nervous and immune systems, the aim of this paper is to present the current state of knowledge and the critical assessment of the role of ω -3 fatty acids in the prophylaxis and treatment of spinal cord injury (SCI) in rodent models. The prophylactic properties (pre-SCI) include the stabilization of neuron cell membranes, the reduction of the expression of inflammatory cytokines (IL-1 β , TNF- α , IL-6, and KC/GRO/CINC), the improvement of local blood flow, reduced eicosanoid production, activation of protective intracellular transcription pathways (dependent on RXR, PPAR- α , Akt, and CREB), and increased concentration of lipids, glycogen, and oligosaccharides by neurons. On the other hand, the therapeutic properties (post-SCI) include the increased production of endogenous antioxidants such as carnosine and homocarnosine, the maintenance of elevated GSH concentrations at the site of injury, reduced concentrations of oxidative stress marker (MDA), autophagy improvement (via increasing the expression of LC3-II), and p38 MAPK expression reduction in the superficial dorsal horns (limiting the sensation of neuropathic pain). Paradoxically, despite the well-documented protective activity of ω -3 acids in rodents with SCI, the research does not offer an answer to the principal question of the optimal dose and treatment duration. Therefore, it is worth emphasizing the role of multicenter rodent studies with the implementation of standards which initially may even be based on arbitrary criteria. Additionally, basing on available research data, the authors of this paper make a careful attempt at referring some of the conclusions to the human population., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Piotr Wojdasiewicz et al.)

Background: The use of adaptive equipment (AE) is the basic indication for patients with spinal cord injury (SCI). Inappropriate decisions concerning the use of AE imply treatment results, patient confidence, and patient and state costs. The present study is the first analysis of the causes of non-compliance conducted in Europe with the provision of AE in SCI patients using Wielandt and Strong's classification., Aim: The aim of this study is to analyze of the causes of non-compliance in the process of providing AE to SCI patients., Design: Retrospective observational study., Setting: "STOCER" Masovian Rehabilitation Centre, Konstancin-Jeziorna, Poland., Population: Seventy-two patients with traumatic SCI 10 months after the completion of the acute and post-acute phases of inpatient rehabilitation., Methods: Wielandt and Strong's classification was used to determine the causes of non-compliance with AE provisions and the present authors' questionnaire with the World Health Organisation Quality of Life (WHOQOL-BREF) were used to identify the risk factors of non-compliance with AE provisions., Results: Non-compliance with prescribed AE provisions was reported in 34 (49.3%) of 69 study participants. Non-compliance was due to medical-related factors in 44.1%, client-related factors in 20.6%, equipment-related factors in 11.8%, and unspecific factors in 17.8% of cases. Non-compliance with AE provisions correlated with complete neurological deficit, preserved ability to walk (in case of wheelchairs), the presence of bedsores (in cases of lower extremity devices), low financial status, and lost ability to walk (in cases of AE for standing and walking). The highest percentage of non-compliance was noted for the provision of knee-ankle-foot orthosis (50%)., Conclusions: The most common causes of non-compliance with AE provisions include health status improvement in the patient and high cost of the device., Clinical Rehabilitation Impact: These results can be helpful for more effective treatment planning and the avoidance of unnecessary reimbursement costs covered by the state and users.

Osteoporosis is a civilization disease which is still challenging for contemporary medicine in terms of treatment and prophylaxis. It results from excessive activation of the osteoclastic cell line and immune cells like macrophages and lymphocytes. Cell-to-cell inflammatory information transfer occurs via factors including cytokines which form a complex network of cell humoral correlation, called cytokine network. Recently conducted studies revealed the participation of CX3CL1 chemokine in the pathogenesis of osteoporosis. CX3CL1 and its receptor CX3CR1 present unique properties among over 50 described chemokines. Apart from its chemotactic activity, CX3CL1 is the only chemokine which may function as an adhesion molecule which facilitates easier penetration of immune system cells through the vascular endothelium to the area of inflammation. The present study, based on world literature review, sums and describes convincing evidences of a significant role of the CX3CL1/CX3CR1 axis in processes leading to bone mineral density (BMD) reduction. The CX3CL1/CX3CR1 axis plays a principal role in osteoclast maturation and binding them with immune cells to the surface of the bone tissue. It promotes the development of inflammation and production of many inflammatory cytokines near the bone surface (i.e., TNF- α , IL-1 β , and IL-6). High concentrations of CX3CL1 in serum are directly proportional to increased concentrations of bone turnover and inflammatory factors in human blood serum (TRACP-5b, NTx, IL-1 β , and IL-6). Regarding the fact that acting against the CX3CL1/CX3CR1 axis is a potential target of immune treatment in osteoporosis, the number of available papers tackling the topic is certainly insufficient. Therefore, it seems justified to continue research which would precisely determine its role in the metabolism of the bone tissue as one of the most promising targets in osteoporosis therapy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Piotr Wojdasiewicz et al.)

Haemophilia A and B are rarely occurring X chromosome-linked congenital coagulation disorders dominated by spontaneous joint bleedings and chronic synovitis, leading to development of haemophilic arthropathy (HA). Progranulin (PGRN) is a growth factor with anti-inflammatory and immunomodulatory properties. PGRN is an important molecule in the pathogenesis of osteoarthritis (OA) and rheumatological disorders. This study was aimed at investigating the potential role of PGRN in the mechanisms underlying the pathogenesis of HA. The serum levels of PGRN were measured by enzyme-linked immunosorbent assay (ELISA) in patients with end-stage knee joint HA (n = 20) and end-stage primary knee joint OA (n = 20) who met the inclusion and exclusion criteria. The clinical and radiological assessment of disease severity was evaluated by the Knee Society Score (KSS) and Kellgren-Lawrence scale. Median PGRN levels in HA patients was 349.1 ng/mL (232.8-415.6 ng/mL) and in OA patients 148.3 ng/mL (112.1-275.3 ng/mL) with statistically significant differences between both groups (P < 0.015). Further analysis revealed no correlation between PGRN levels and any of the patient demographics and clinical parameters. This study demonstrates increased PGRN serum levels in patients with HA and provides new insights into the mechanisms underlying the pathogenesis of HA indicating a new potential target for therapeutic intervention., (© 2018 John Wiley & Sons Australia, Ltd.)

Objectives: Inflammatory processes in rheumatic diseases spread via various types of immune system cells and tissues with the aid of inflammatory cytokines and growth factors and the participation of vascular endothelium. Research is still conducted to determine the role of individual factors in the pathophysiology of rheumatic diseases. The task is complicated because the multiplane network of cytokines is characterized by complex correlations manifesting as positive and negative feedback, which impedes the definitive interpretation of the role of specific cytokines. Therefore, it seems justified to perform a comparative analysis of the expression of at least several molecules in one study, which may help reveal their role in the pathogenesis of rheumatic diseases and have prognostic value., Material and Methods: The aim of the study involves the assessment and comparative analysis of the concentrations of interleukin 35 (IL-35), tumour necrosis factor α (TNF-α), B-cell-activating factor (BAFF), and vascular endothelial growth factor (VEGF) in peripheral blood serum in patients with rheumatoid arthritis (RA) ( n = 43), systemic lupus erythematosus (SLE) ( n = 28), antiphospholipid syndrome (APS) ( n = 24), and mixed connective tissue disease (MCTD) ( n = 9). The main intention is to search for biomarkers for specific rheumatic diseases. Cytokine and growth factor levels were determined using specific ELISA kits., Results: Statistically significant differences in VEGF and IL-35 concentrations occurred between patients with APS vs. RA and SLE vs. RA. There was a significant high positive correlation between the concentration of BAFF and TNF-α ( r = 0.77, p < 0.0000) in patients with APS, as well as in patients with SLE ( r = 0.55, p = 0.00)., Conclusions: BAFF and TNF-α may be promising biomarkers in patients with APS and VEGF in patients with RA. Additionally, IL-35 may be a useful marker for the diagnosis of APS. Positive correlation of BAFF and TNF-α concentrations in APS and SLE potentially indicates much more similar etiopathogenesis of these diseases than it could be previously predicted., Competing Interests: The authors declare no conflict of interest.

Hemophilic arthropathy (HA) is one of the most common and typical manifestation in the course of recurrent bleeding episodes in patients with hemophilia. Clinical and subclinical joint bleeding episodes gradually lead to irreversible changes manifesting themselves as pain, progressing ankylosis, marked limitation of the range of motion, muscle atrophy and osteoporosis commonly concomitant with joint deformity resulting from chronic proliferative synovitis and both cartilage and bone degeneration leading to the final functional impairment of the joint. In spite of numerous studies, the pathophysiology of HA has not been fully elucidated, especially as regards immunopathological mechanisms which are associated with the subclinical and early stage of the disease and to be more precise, with chronic joint inflammation. It needs to be emphasized that the pathophysiological processes occurring in a joint with HA are most probably highly mediated by interactions within the cytokine network and other inflammatory mediators present in the tissues of affected joint. Among numerous compounds participating in the induction of an inflammatory process in the pathogenesis of HA, cytokines seem to play a leading role. The most important group controlling the disease seems to be well known inflammatory cytokines, including IL-1β, TNFα and IL-6. The second group with antagonistic effect is formed by anti-inflammatory cytokines such as IL-4 and IL-10. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of HA with respect to cellular and intracellular signaling pathways is still under investigation. This review, summarizes and discusses the current knowledge about cytokine network in the pathogenesis of HA, indicating possible molecular and cellular mechanisms that may provide potential new therapeutic directions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To investigate whether a difference exists between DAS28 from CRP and DAS28 from ESR in patients with rheumatoid arthritis (RA) and secondary Sjögren's syndrome (sSS)., Material and Methods: One group comprised patients with RA and sSS, the control group comprised patients with RA. The inclusion criteria for the RA and sSS group have been specified as follows: presence of at least one symptom of dryness, and also presence of anti-SS-A and anti-SS-B or at least focus score of one in biopsy., Results: The disease activity score 28 (DAS28) was assessed using both ESR and CRP in 60 patients with RA and sSS and 59 patients with RA alone. However, concordance between these two methods was good (Cohen's κ coefficient κ = 0.60, 95% CI: 0.45-0.75 in the first group and κ = 0.71, 95% CI: 0.56-0.86 in the control group). In the group with RA and sSS, the mean value of DAS28-ESR = 5.2, whereas the mean value of DAS28-CRP = 4.7 (p < 0.0001). In the group with RA alone, mean DAS28-ESR = 4.7 while mean DAS28-CRP = 4.6; no significant difference was identified. Moreover, in RA patients with sSS, mean ESR = 39 mm/h compared with mean CRP at 25 mg/l. 79% of all patients demonstrated dysproteinaemia. There were connections between higher ESR and dysproteinaemia. In the control group there was no statistically significant difference between CRP and ESR., Conclusions: Both DAS28-ESR and DAS28-CRP are useful outcome measures in RA. However, in patients with RA and sSS, DAS28 should be evaluated based on CRP.

The transforming growth factor beta (TGF-β) family forms a group of three isoforms, TGF-β1, TGF-β2, and TGF-β3, with their structure formed by interrelated dimeric polypeptide chains. Pleiotropic and redundant functions of the TGF-β family concern control of numerous aspects and effects of cell functions, including proliferation, differentiation, and migration, in all tissues of the human body. Amongst many cytokines and growth factors, the TGF-β family is considered a group playing one of numerous key roles in control of physiological phenomena concerning maintenance of metabolic homeostasis in the bone tissue. By breaking the continuity of bone tissue, a spread-over-time and complex bone healing process is initiated, considered a recapitulation of embryonic intracartilaginous ossification. This process is a cascade of local and systemic phenomena spread over time, involving whole cell lineages and various cytokines and growth factors. Numerous in vivo and in vitro studies in various models analysing cytokines and growth factors' involvement have shown that TGF-β has a leading role in the fracture healing process. This paper sums up current knowledge on the basis of available literature concerning the role of the TGF-β family in the fracture healing process.

Chronic non-bacterial osteomyelitis (CNO) has been known for over of 40 years. It is an underrecognized entity due to the low number of described cases and poor propagation awareness of the problem. Chronic non-bacterial osteomyelitis is usually confused with infectious spondylodiscitis or malignant lesions, both primary and metastatic. Failing to consider CNO as one of possible lesions of the spine among an array of differential diagnoses may lead to a prolonged ineffective treatment increasing treatment-related morbidity. In this paper the authors describe these two syndromes, with a possible autoimmune background - chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO syndrome - that include CNO being among the manifestations. The authors present the spinal symptomatology of CNO for both syndromes published so far to help spine clinicians organize the information for better usage in everyday clinical practice.

Fractures of calcaneus are the most common among all tarsal bone fractures. Such injuries are most often produced by large forces, while accompanying soft tissue trauma makes them complicated and difficult to treat. Due to complex structure of the foot and talocalcaneal joint all injuries to this area constitute an important orthopedic problem, as improper treatment or lack thereof leads to gait impairment, particularly with regard to moving on uneven surface. In this work we presented the problem of intraarticular calcaneal fractures with particular consideration paid to methods of its treatment. We also mentioned the problem of complications after conservative and surgical treatment as well as methods of their prevention.

Osteoarthritis (OA) is the most common chronic disease of human joints. The basis of pathologic changes involves all the tissues forming the joint; already, at an early stage, it has the nature of inflammation with varying degrees of severity. An analysis of the complex relationships indicates that the processes taking place inside the joint are not merely a set that (seemingly) only includes catabolic effects. Apart from them, anti-inflammatory anabolic processes also occur continually. These phenomena are driven by various mediators, of which the key role is attributed to the interactions within the cytokine network. The most important group controlling the disease seems to be inflammatory cytokines, including IL-1 β , TNF α , IL-6, IL-15, IL-17, and IL-18. The second group with antagonistic effect is formed by cytokines known as anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of OA with respect to inter- and intracellular signaling pathways is still under investigation. This paper summarizes the current state of knowledge. The cytokine network in OA is put in the context of cells involved in this degenerative joint disease. The possibilities for further implementation of new therapeutic strategies in OA are also pointed.

Background: Spontaneous intraarticular bleeds in congenital coagulation disorders result in early and extensive damage to the joints and periarticular structures. Total arthroplasty is the only effective method of treating these defects. Interim surgical procedures (arthroscopy, osteotomy, etc.) exist that can postpone arthroplasty, especially considering the fact that the condition affects young people. The aim of this paper is to discuss the range of trauma care and orthopedic procedures performed in patients with congenital coagulation disorders. Also presented are early results of joint arthroplasty in these patients., Material and Methods: A total of 168 trauma care and orthopedic procedures were performed in patients with congenital coagulation disorders at the Clinical Department of Orthopedics and Traumatology of the Central Clinical Hospital of the Ministry of Interior in Warsaw in the years 2010-2013. Among them were total arthroplasties (79 arthroplasties of the knee, 30 of the hip, 3 of the ankle and 1 of the elbow), arthroscopies, filling bone cysts with grafts and trauma procedures. The HHS, KSS, AOFAS and MEPS scales were used to evaluate the respective clinical results of hip, knee, ankle and elbow arthroplasty procedures. A VAS was used to evaluate pain intensity. In knee arthroplasty patients, quality of life parameters were evaluated with the WOMAC index., Results: In patients post hip arthroplasty, HHS scores increased by 50.22 points and VAS scores increased by 6.34 points. An increase of 116.41 points in KSS scores and 6.67 points in VAS scores was recorded in patients after knee arthroplasty. Also, WOMAC scores improved by 53.8 points after surgery. Evaluation of early results of ankle arthroplasty in the AOFAS scale showed a mean improvement of 35.5 points and a 5-point improvement in VAS scores. MEPS scores, used for evaluation of elbow arthroplasty results, improved from 15 to 70 points, with an improvement from 6 to 2 points in VAS scores., Conclusions: 1. Orthopedic procedures in patients with congenital coagulation disorders require thorough preparation of the patient and close cooperation between the orthopedic and hematological teams. 2. Early clinical outcomes are promising. 3. Decreased pain intensity, increased joint range of motion and improved quality of life post-surgery are observed.