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 Ischemic Stroke.

Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines. Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.

Post-mortem detection of neuronal and astroglial biochemical markers in serum and urine for diagnostics of traumatic brain injury.

Currently available epidemiological data shows that traumatic brain injury (TBI) represents one of the leading causes of death that is associated with medico-legal practice, including forensic autopsy, criminological investigation, and neuropathological examination. Attention focused on TBI research is needed to advance its diagnostics in ante- and post-mortem cases with regard to identification and validation of novel biomarkers. Recently, several markers of neuronal, astroglial, and axonal injury have been explored in various biofluids to assess the clinical origin, progression, severity, and prognosis of TBI. Despite clinical usefulness, understanding their diagnostic accuracy could also potentially help translate them either into forensic or medico-legal practice, or both. The aim of this study was to evaluate post-mortem pro-BDNF, NSE, UCHL1, GFAP, S100B, SPTAN1, NFL, MAPT, and MBP levels in serum and urine in TBI cases. The study was performed using cases (n = 40) of fatal head injury and control cases (n = 20) of sudden death. Serum and urine were collected within ∼ 24 h after death and compared using ELISA test. In our study, we observed the elevated concentration levels of GFAP and MAPT in both serum and urine, elevated concentration levels of S100B and SPTAN1 in serum, and decreased concentration levels of pro-BDNF in serum compared to the control group. The obtained results anticipate the possible implementation of performed assays as an interesting tool for forensic and medico-legal investigations regarding TBI diagnosis where the head injury was not supposed to be the direct cause of death.

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.

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.

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.

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.

Effects of α-Synuclein Monomers Administration in the Gigantocellular Reticular Nucleus on Neurotransmission in Mouse Model.

The aim of the study was to examine the Braak's hypothesis to explain the spreading and distribution of the neuropathological changes observed in the course of Parkinson's disease among ascending neuroanatomical regions. We investigated the neurotransmitter levels (monoamines and amino acid concentration) as well as tyrosine hydroxylase (TH) and transglutaminase-2 (TG2) mRNA expression in the mouse striata (ST) after intracerebral α-synuclein (ASN) administration into gigantocellular reticular nucleus (Gi). Male C57BL/10 Tar mice were used in this study. ASN was administrated by stereotactic injection into Gi area (4 µl; 1 µg/µl) and mice were decapitated after 1, 4 or 12 weeks post injection. The neurotransmitters concentration in ST were evaluated using HPLC detection. TH and TG2 mRNA expression were examined by Real-Time PCR method. At 4 and 12 weeks after ASN administration we observed decrease of DA concentration in ST relative to control groups and we found a significantly higher concentration one of the DA metabolites-DOPAC. At these time points, we also noticed the increase in DA turnover determined as DOPAC/DA ratio. Additionally, at 4 and 12 weeks after ASN injection we noted decreasing of TH mRNA expression. Our findings corresponds with the Braak's theory about the presence of the first neuropathological changes within brainstem and then with time affecting higher neuroanatomical regions. These results obtained after administration of ASN monomers to the Gi area may be useful to explain the pathogenesis of Parkinson's disease.

Presence of Toxoplasma gondii infection in brain as a potential cause of risky behavior: a report of 102 autopsy cases.

Toxoplasmosis was linked to impairment in brain function, encompassing a wide range of behavioral and neuropsychiatric changes. Currently, the precise localization of Toxoplasma gondii in the human brain is limited and the parasite DNA was not found in population-based screening of autopsy cases. The aim of proposed study was to identify the presence of parasite DNA within the brain and its association with risky behavior and alcohol consumption in postmortem examination. Preliminarily, 102 cases with certain circumstances of death at time of forensic autopsy was included. Due to high risk of bias, the females were excluded from the analysis and final study group consists 97 cases divided into three groups: risky behavior, inconclusively risky behavior, and control group. The obtained tissue samples for Nested PCR covered four regions of the brain: symmetric left/right and anterior/posterior horns of lateral ventricles comprising lining ependyma and hippocampus. The second type of material comprised blood evaluated for antibodies prevalence using ELISA and alcohol concentration using HS-GC-FID. Analysis demonstrated 16.5% prevalence concerning the parasite DNA presence in examined brain tissue samples without specific distribution and association with age at death or days after death until an autopsy was performed. Results have shown correlation between occurrence of risky behavior leading to death and higher proportions of positive parasite DNA presence within the brain. Correlation was not observed between parasite DNA presence and excessive alcohol consumption. Conducted screening demonstrated correlation between parasite DNA presence in the brain with risky behavior and provided new information on possible effects of latent toxoplasmosis.

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.

Brain Functional Reserve in the Context of Neuroplasticity after Stroke.

Stroke is the second cause of death and more importantly first cause of disability in people over 40 years of age. Current therapeutic management of ischemic stroke does not provide fully satisfactory outcomes. Stroke management has significantly changed since the time when there were opened modern stroke units with early motor and speech rehabilitation in hospitals. In recent decades, researchers searched for biomarkers of ischemic stroke and neuroplasticity in order to determine effective diagnostics, prognostic assessment, and therapy. Complex background of events following ischemic episode hinders successful design of effective therapeutic strategies. So far, studies have proven that regeneration after stroke and recovery of lost functions may be assigned to neuronal plasticity understood as ability of brain to reorganize and rebuild as an effect of changed environmental conditions. As many neuronal processes influencing neuroplasticity depend on expression of particular genes and genetic diversity possibly influencing its effectiveness, knowledge on their mechanisms is necessary to understand this process. Epigenetic mechanisms occurring after stroke was briefly discussed in this paper including several mechanisms such as synaptic plasticity; neuro-, glio-, and angiogenesis processes; and growth of axon.

The role of progranulin (PGRN) in the modulation of anti-inflammatory response in asthma.

Asthma is one of the most common chronic diseases. Epidemiological studies show that asthma will develop among around 40% of children under six years old with symptoms of bronchial obstruction. Diagnosis of asthma is complicated, especially in the paediatric population. As a result, a lot of research is being carried out to establish the pathophysiology and to find new biomarkers of this disease. Progranulin (PGRN) is a recently discovered growth factor with many biological functions. PGRN has anti-inflammatory properties because it inhibits neutrophil degranulation and blocks tumor necrosis factor α (TNF-α) transmission. The underlying mechanisms are still being researched, but TNF-α is considered to be a cytokine responsible for neutrophilic inflammation in the airways and bronchial hyperresponsiveness. Therefore, PGRN, by lowering TNF-α concentration and stimulating regulatory T-cell (Treg) proliferation, relieves symptoms of bronchial inflammatory diseases. This article attempts to verify the current knowledge about basic pathophysiological mechanisms in asthma. We also summarise the most recent research advances in the role of PGRN in the respiratory system.

Oblique corpectomy in the cervical spine.

STUDY DESIGN: A narrative review. OBJECTIVES: A literature review of studies reporting on the application of oblique corpectomy (OC) in various pathologies of the cervical spine. SETTING: UK. METHODS: A search was carried out using the PubMed and Google Scholar up to 18 March 2017. Finally, 26 studies met the inclusion criteria. RESULTS: A multilevel OC shows good clinical outcomes in various pathologies in the cervical spine. The clinical improvement in cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament was found to be over 70%. OC allows wide anterior decompression of the spinal cord and complete unilateral nerve root decompression. The approach carries a risk of Horner's syndrome, vertebral artery and accessory nerve injury. OC does not compromise spine stability and osteoarthrodesis with bone grafting is not necessary. Spinal motions are preserved and appear close to normal. OC can be applied in patients with a low fusion rate such as the elderly, diabetics, and heavy smokers. Furthermore, OC was found to be an optimal approach for exta-intradural tumors of the cervical spine. CONCLUSIONS: OC seems to be a valid alternative for the management of multisegmental CSM in selected cases. It should not be considered a first-line treatment strategy due to the relatively high morbidity. There are no studies comparing OC without fusion to other treatment options in CSM. Therefore, rigorous prospective studies using validated outcome measures with long-term follow-up are required.

Transforming growth factor Beta family: insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications.

The transforming growth factor beta (TGF-ß) family forms a group of three isoforms, TGF-ß1, TGF-ß2, and TGF-ß3, with their structure formed by interrelated dimeric polypeptide chains. Pleiotropic and redundant functions of the TGF-ß 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-ß 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-ß 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-ß family in the fracture healing process.

Syndromes with chronic non-bacterial osteomyelitis in the spine.

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 role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis.

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 ß , 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.

Effect of whole-body vibration on postural stability in young adults with generalized joint hypermobility: A comparative study.

BACKGROUND: Whole-body vibration (WBV) is being used in rehabilitation and sport. Studies confirm its positive impact on muscle strength and power or regulating muscle hypertension. However, there are some uncertainties regarding its influence on postural stability. This issue seems particularly interesting in the case of individuals with generalized joint hypermobility (GJH), for whom proprioceptive training and muscle strengthening exercises are recommended while techniques that decrease muscle tension are not advised. OBJECTIVE: The aim of the study was to evaluate the acute effect of WBV on postural stability in adults with GJH. METHODS: 60 participants were categorized into the groups: 1) hypermobility with vibration (GJH+WBV), 2) hypermobility without vibration (GJH-WBV), 3) control group with vibration (CTRL+WBV), 4) control group without vibration (CTRL-WBV). The first and the third group completed WBV (frequency: 15 Hz and 30 Hz, amplitude 3 mm, 3 × 3 min). The second and fourth groups participated only in measurement sessions. GJH was assessed using the Beighton test. Postural stability was measured as the overall stability index (OSI) on the Biodex Balance System on the stable and unstable platform with open and closed eyes. Measurements were taken before and after WBV for two weeks. RESULTS: At a frequency of 15 Hz, a significant time effect was observed for measurements Before and After in CTRL-WBV on the stable platform with open eyes (p= 0.012) and on the unstable platform with closed eyes (p= 0.000) for the GJH+WBV and CTRL+WBV groups. There were no significant interactions (p> 0.05) between factors. At a frequency of 30 Hz, there was a significant time effect Before and After (p= 0.047) on the stable platform with open eyes, but no interaction was found between factors (p= 0.835). CONCLUSION: There is no positive acute effect of WBV on postural stability in adults with and without GJH.

Dose-Ranging Effects of the Intracerebral Administration of Atsttrin in Experimental Model of Parkinson's Disease Induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Mice.

Parkinson's disease is one of the most common neurodegenerative disorders characterized by a multitude of motor and non-motor clinical symptoms resulting from the progressive and long-lasting abnormal loss of nigrostriatal dopaminergic neurons. Currently, the available treatments for patients with Parkinson's disease are limited and exert only symptomatic effects, without adequate signs of delaying or stopping the progression of the disease. Atsttrin constitutes the bioengineered protein which ultrastructure is based on the polypeptide chain frame of the progranulin (PGRN), which exerts anti-inflammatory effects through the inhibition of TNFα. The conducted preclinical studies suggest that the therapeutic implementation of Atsttrin may be potentially effective in the treatment of neurodegenerative diseases that are associated with the occurrence of neuroinflammatory processes. The aim of the proposed study was to investigate the effect of direct bilateral intracerebral administration of Atsttrin using stereotactic methods in the preclinical C57BL/6 mouse model of Parkinson's disease inducted by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. The analysis of the dose dependency effects of the increasing doses of Atsttrin has covered a number of parameters and markers regarding neurodegenerative processes and inflammatory responses including IL-1α, TNFα, IL-6, TH, and TG2 mRNA expressions. Accordingly, the evaluation of the changes in the neurochemical profile included DA, DOPAC, 3-MT, HVA, NA, MHPG, 5-HT, and 5-HIAA concentration levels. The intracerebral administration of Atsttrin into the striatum effectively attenuated the neuroinflammatory reaction in evaluated neuroanatomical structures. Furthermore, the partial restoration of monoamine content and its metabolic turnover were observed. In this case, taking into account the previously described pharmacokinetic profile and extrapolated bioavailability as well as the stability characteristics of Atsttrin, an attempt was made to describe as precisely as possible the quantitative and qualitative effects of increasing doses of the compound within the brain tissue microenvironment in the presented preclinical model of the disease. Collectively, this findings demonstrated that the intracerebral administration of Atsttrin may represent a potential novel therapeutic method for the treatment of Parkinson's disease.

Salidroside: A Promising Agent in Bone Metabolism Modulation.

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.

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.