The Role of Rosavin in the Pathophysiology of Bone Metabolism.

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.

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

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.

The 4DBODY system as a new tool for chest mobility assessment in patients with ankylosing spondylitis.

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.

Mast Cell Activation Syndrome in COVID-19 and Female Reproductive Function: Theoretical Background vs. Accumulating Clinical Evidence.

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.

Omega-3 fatty acids in the treatment of spinal cord injury: untapped potential for therapeutic intervention?

Omega-3 fatty acids constitute a group of fatty acids with anti-inflammatory and preventive effects against various diseases. Studies in animal models have demonstrated the preventive and therapeutic effects of omega-3 fatty acids after spinal cord injury (SCI) in reducing inflammatory reactions and promoting neuroregeneration. However, studies on the efficacy of omega-3 fatty acids in treatment and prevention after SCI seem to be questionable. This study evaluates potential reasons for omega-3 fatty acid therapy oversight in populations after SCI. Therefore, some of the reasons could cover heterogeneous patient groups in size, level of injury, quality of life assessment, time since injury, no single standardised dose, various follow-up durations and metabolic changes, often insufficient to record. Due to the difficulty of collecting cases for the study, especially in the acute phase after SCI, multicenter, coordinated studies are needed to establish the effects of omega-3 fatty acids on treatment, recovery, and disease prevention in patients after SCI. Although the present results of such studies are still inconclusive, the failure to exploit the potential properties of omega-3 fatty acids in the treatment of patients with SCI solely due to methodological difficulties should be considered a potential waste.

The role of inflammatory mediators in the pathogenesis of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome.

INTRODUCTION: As a recurrent disease, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is characterized by episodes of febrile attacks and is often prominent in children under five years of age. However, the etiology of this condition has not been fully understood yet. MATERIALS AND METHODS: The search in the extensive literature of peer-reviewed articles published from the inception to December 2021 was conducted to identify the relevant studies, using the electronic databases of MEDLINE/PubMed, Embase, Scopus, the Cochrane Library, and the Web of Science. RESULTS: The analysis of complex relationships indicates that inflammatory factors, such as various cytokines and acute-phase proteins (APPs), play leading roles in the pathogenesis of this disease. Accordingly, this article summarizes the current state of knowledge to explain the mechanisms involved in inflammatory responses among patients with PFAPA syndrome and investigate its role in the pathogenesis of this disease. Moreover, the possibilities for further implementation of new therapeutic strategies are pointed out. CONCLUSION: It is concluded that some pathophysiological processes are associated with immune dysregulation, which itself may be secondary to environmental factors, genetic background, and underlying diseases, including latent infections that multiply inflammatory mediators. elevated inflammatory markers similarly play a significant part in the clinical outcomes of this condition, whose pyrogenic nature is the reason for the development of episodes of febrile attacks in the population of patients suffering from PFAPA syndrome.

Involvement of progranulin (PGRN) in the pathogenesis and prognosis of breast cancer.

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.

Adherence to prescriptions of therapeutic exercises in patients with traumatic spinal cord injury.

INTRODUCTION: 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. MATERIAL 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.

The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding.

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.

Skin surface infrared thermography in pressure ulcer outcome prognosis.

OBJECTIVE: To assess the usefulness of skin surface infrared thermography (SSIT) as a prognostic tool in the treatment of stages III and IV pressure ulcers (PU), with hydrocolloid/hydrogel dressings plus 20 exposures to low-level laser therapy (LLLT), compared with hydrocolloid dressings alone, in a group of long-term bedbound care patients. METHOD: In this comparative study, participants were randomly assigned to group I: PUs treated with specialist wound dressings and laser therapy, or to group II: PUs treated with specialist wound dressings without laser therapy. Thermal imaging sessions were carried out at the beginning of the study, and after two and four weeks of treatment. Thermal imaging processing was applied to compare percentage differences in the temperature distribution between the groups within selected regions of interest (ROIs). The correlation between the temperature distribution and PU healing was evaluated. RESULTS: A total of 43 patients took part. In the study, three variants of PU healing were observed: pure healing (H) with minimal granulation; healing with hypergranulation (H+G); and non-healing (NH). Analyses of SSIT-related thermographic patterns revealed their dependence on the course of healing. The percentage of successful PU healing reached 79.2% in group I compared with 73.7% in group II (p<0.05) The dominant variant of healing in Group I was H, while in group II the variants H and H+G were present with equal frequency. CONCLUSION: Thermal imaging processing allowed comparison of differences in the temperature distribution between the groups within ROIs. Application of LLLT significantly improved the healing process (p<0.05). The clinical significance of this finding should be confirmed with larger studies; however, SSIT may be useful as a prognostic tool during the treatment of PUs, with the ability to predict the course of healing initially, that is independent of LLLT treatment.

Corrigendum to "Comparative Analysis of the Occurrence and Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Hemophilic Arthropathy and Osteoarthritis".

[This corrects the article DOI: 10.1155/2020/2932696.].

Comparative Analysis of the Occurrence and Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Hemophilic Arthropathy and Osteoarthritis.

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.

Significance of Omega-3 Fatty Acids in the Prophylaxis and Treatment after Spinal Cord Injury in Rodent Models.

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-1ß, 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.

Compliance with prescriptions for wheelchairs, walking aids, orthotics, and pressure-relieving devices in patients with traumatic spinal cord injury.

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.

Role of CX3CL1/CX3CR1 Signaling Axis Activity in Osteoporosis.

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-1ß, 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-1ß, 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.

IL-35, TNF-α, BAFF, and VEGF serum levels in patients with different rheumatic diseases.

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.

Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy.

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.

Cytokines in the pathogenesis of hemophilic arthropathy.

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-1ß, 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.

Analysis of the Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Traumatic Brain and Spinal Cord Injury: Insight into Recent Advances in Actions of Neurochemokine Agents.

CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its biological properties through interaction with one dedicated CX3CR1 receptor which belongs to a family of G protein-coupled receptors (GPCR). The CX3CL1/CX3CR1 axis acts in many physiological phenomena including those occurring in the central nervous system (CNS), by regulating the interactions between neurons, microglia, and immune cells. Apart from the role under physiological conditions, the CX3CL1/CX3CR1 axis was implied to have a role in different neuropathologies such as traumatic brain injury (TBI) and spinal cord injury (SCI). CNS injuries represent a serious public health problem, despite improvements in therapeutic management. To date, no effective treatment has been determined, so they constitute a leading cause of death and severe disability. The course of TBI and SCI has two consecutive poorly demarcated phases: the initial, primary injury and secondary injury. Recent evidence has implicated the role of the CX3CL1/CX3CR1 axis in neuroinflammatory processes occurring after CNS injuries. The importance of the CX3CL1/CX3CR1 axis in the pathophysiology of TBI and SCI in the context of systemic and direct local immune response is still under investigation. This paper, based on a review of the literature, updates and summarizes the current knowledge about CX3CL1/CX3CR1 axis involvement in TBI and SCI pathogenesis, indicating possible molecular and cellular mechanisms with a potential target for therapeutic intervention.

Discrepancies in assessment of patients with rheumatoid arthritis and secondary Sjögren's syndrome by DAS28-ESR and DAS28-CRP.

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.