A novel insight into the neuroprotective effects of cannabidiol: maintained apelin/dopamine synthesis, NRF2 signaling, and AKT/CREB/BDNF gene expressions.

Neuroinflammation is a process associated with degeneration and loss of neurons in different parts of the brain. The most important damage mechanisms in its formation are oxidative stress and inflammation. This study aimed to investigate the protective effects of cannabidiol (CBD) against neuroinflammation through various mechanisms. Thirty­two female rats were randomly divided into 4 groups as control, lipopolysaccharide (LPS), LPS + CBD and CBD groups. After six hours following LPS administration, rats were sacrificed, brain and cerebellum tissues were obtained. Tissues were stained with hematoxylin­eosin for histopathological analysis. Apelin and tyrosine hydroxylase synthesis were determined immunohistochemically. Total oxidant status and total antioxidant status levels were measured, and an oxidative stress index was calculated. Protein kinase B (AKT), brain-derived neurotrophic factor (BDNF), cyclic­AMP response element­binding protein (CREB) and nuclear factor erythroid 2­related factor 2 (NRF2) mRNA expression levels were also determined. In the LPS group, hyperemia, degeneration, loss of neurons and gliosis were seen in all three tissues. Additionally, Purkinje cell loss in the cerebellum, as well as neuronal loss in the cerebral cortex and hippocampus, were found throughout the LPS group. The expressions of AKT, BDNF, CREB and NRF2, apelin and tyrosine hydroxylase synthesis all decreased significantly. CBD treatment reversed these changes and ameliorated oxidative stress parameters. CBD showed protective effects against neuroinflammation via regulating AKT, CREB, BDNF expressions, NRF2 signaling, apelin and tyrosine hydroxylase synthesis.

The ameliorative effects of cannabidiol on methotrexate-induced neuroinflammation and neuronal apoptosis via inhibiting endoplasmic reticulum and mitochondrial stress.

Methotrexate (MTX) is an antineoplastic agent and has neurotoxic effects. It exerts its toxic effect on the brain by triggering inflammation and apoptosis. Cannabidiol (CBD) is an agent known for its antioxidant, anti-inflammatory effects in various tissues. The aim of this study is to examine the protective effects of CBD treatment in various brain structures from MTX damage and to evaluate the effect of intracellular pathways involved in apoptosis. Thirty-two adult Wistar Albino female rats were divided into four groups as control, MTX (20 mg/kg intraperitoneally [i.p.]), MTX + CBD (0.1 mL of 5 mg/kg i.p.), and CBD (for 7 days, i.p.). At the end of the experiment, brain tissues collected for biochemical analyses as total oxidant status (TOS), total antioxidant status, oxidative stress index (OSI), histopathological and immunohistochemical analyses as tumor necrosis factor-α (TNF-α), serotonin, mammalian target of rapamycin (mTOR) staining, genetic analyses as caspase-9 (Cas-9), caspase-12 (Cas-12), C/EBP homologous protein (CHOP), and cytochrome-c (Cyt-c) gene expressions. In the histopathological and immunohistochemical evaluation, hyperemia, microhemorrhage, neuronal loss, and significant decreasing expressions of seratonin were observed in the cortex, hippocampus, and cerebellum regions in the MTX group. mTOR, TNF-α, Cas-9, Cas-12, CHOP, and Cyt-c expressions with TOS and OSI levels were increased in the cortex. It was observed that these findings were reversed after CBD application in all regions. MTX triggers neuronal apoptosis via endoplasmic reticulum and mitochondrial stress while destroying serotonergic neurons. The reversal of the pathological changes with CBD treatment proves that it has anti-inflammatory and antiapoptotic activity in brain.

Systemic Immune Inflammation Index as a Reliable Disease Activity Marker in Psoriatic Arthritis.

OBJECTIVE: To assess the utility of systemic immune inflammation index (SII) in predicting disease activity in psoriatic arthritis (PsA) patients. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Diskapi Yildirim Beyazit Research and Training Hospital, Ankara, Turkey, from October 2020 to September 2021. METHODOLOGY: This study included 106 PsA and 103 age and gender-matched healthy individuals. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), and SII were calculated from complete blood count parameters. The PsA disease activity was assessed by using disease activity score-ESR and DAS-CRP based on 28 joints and the Disease Activity in Psoriatic Arthritis (DAPSA) scores. The receiver operating characteristic (ROC) curve was performed to evaluate the utility of SII in determining disease activity in PsA patients. RESULTS: The NLR, PLR, MLR, and SII were significantly higher in PsA patients compared to healthy control (p=0.013, p=0.019, p=0.012, and p=0.002, respectively). There were statistically significant positive correlations between the DAS28-ESR, DAS28-CRP, and DAPSA and SII (p<0.001, p<0.001, and p<0.001 respectively). The SII values were significantly higher in PsA patients with moderate to severe disease activity according to DAPSA scores when compared to patients with remission or low disease activity (p<0.001). The cut-off value of 800x109/L was found for predicting disease activity in PsA. CONCLUSION: SII may be an easy, practical, economical, and readily accessible tool for monitoring disease activity and the efficacy of treatment in PsA patients. KEY WORDS: Blood cell count, Psoriatic arthritis, Systematic immune inflammation index (SII).

Indications and risk factors for hospitalization in patients with primary Sjögren syndrome: experience from a tertiary center in Turkey.

OBJECTIVE: In this study, it was aimed to reveal the hospitalization reasons for patients diagnosed with primary Sjögren syndrome (pSS) and potentially associated factors in a tertiary health center. METHOD: One hundred and sixty-three pSS patients who regularly attended their follow-ups between January 2010 and May 2021 were included in the study. These patients' reasons for hospitalization, duration of hospitalization, and numbers of presenting to the hospital were recorded. The demographic, clinical and serological characteristics of the hospitalized and non-hospitalized patients were compared. RESULTS: Hospitalization occurred in 22.7% of the patients, and the total number of hospitalizations was 79. The hospitalization incidence density rate was 6.21 per 100 patient-years. The most frequently encountered reason for hospitalizations was pSS-related organ involvement (44.3%). Infections (17.7%), malignancy (16.5%), endocrine, and various other reasons were the other indications for hospitalization. While male sex (p = 0.005), the presence of extra-glandular involvement (p < 0.001), and interstitial lung disease (p = 0.001) were more common in the hospitalized patients, anti-nuclear antibody positivity was less frequent (p = 0.032). The usage rate of hydroxychloroquine (p = 0.022) was lower in the hospitalized patients, whereas the use of glucocorticoids (p < 0.001) and azathioprine (p = 0.005) was more frequent. The multivariable analyses revealed a relationship between extra-glandular involvement (OR: 4.57 [1.05-19.84], p = 0.043), glucocorticoid use (OR: 3.23 [1.13-9.21], p = 0.028) and hospitalization. CONCLUSION: pSS-related system involvement and infection accounted for the majority of hospitalizations of the pSS patients. The presence of extra-glandular involvement and glucocorticoid use were found to be associated with hospitalization. Key Points • pSS-related system involvement and infection accounted for the majority of hospitalizations of pSS patients. • The presence of extra-glandular involvement was found to be associated with hospitalization.

Disseminated Nocardiosis with Ocular Involvement in a Patient with Anca-associated Vasculitis.

A 62-year male patient, diagnosed with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), developed proptosis and decrease in visual acuity while on rituximab treatment. As the ophthalmological examination and imaging studies could not exclude tumour of the orbit, enucleation of the orbit was performed. The histopathology displayed necrosis and inflammation. Because the clinical, laboratory and pathological findings of the patient suggested a vasculitis exacerbation, the immunosuppressive treatment was continued. However, the patient developed confusion and hemiplegia with cerebral mass lesions on imaging. The subsequent report of the pathology revealed a nocardial infection of the eye. The patient was diagnosed with nocardiosis with ocular and cerebral involvement. Despite efficient antimicrobial therapy, the disease progressed rapidly causing death. This case is unique as it describes disseminated nocardiosis with ocular and cerebral involvement in an AVV patient. Key Words: Immunosuppression, Nocardiosis, ANCA-associated vasculitis, Proptosis.

Evaluation of In Vivo Adhesion Properties of New Generation Polyglactin, Oxidized Regenerated Cellulose and Chitosan-Based Meshes for Hernia Surgery.

Introduction Composite meshes coated with anti-adhesive barriers have been developed by taking advantage of the robustness of polypropylene meshes for use in hernia repair. We aimed to evaluate the effects of composite meshes containing polyglactin, polycaprolactone, oxidized regenerated cellulose and chitosan on the adhesion formation. Methods Forty-two Sprague Dawley male rats were divided into six groups of seven rats according to the content of the meshes used. A defect was created on the right abdominal wall of the rats and an oval composite mesh of 2 cm in diameter was placed over the defect and fixed. The rats were sacrificed under anesthesia on the 7th postoperative day. Macroscopic and histopathological examination was performed and the incorporation of the mesh with the abdominal wall and the presence of intraabdominal adhesions were evaluated. Results When the macroscopic findings of the rats were evaluated, there was a statistically significant difference between the rat groups in terms of the distribution of peritoneal adhesion scores (p<0.05). There was no statistically significant difference between the rat groups in terms of the distribution of inflammation, fibrosis and macrophage levels (p>0.05). Conclusion It was evaluated that the development of intraabdominal adhesion and the strength of adhesion decreased when biocompatible adhesion barriers with anti-adhesive properties such as oxidized regenerated cellulose and chitosan were used in the structure of composite meshes used in hernia repair. Hemostatic and antibacterial properties of these substances are promising to create the ideal mesh.

Zero-valent iron nanoparticles containing nanofiber scaffolds for nerve tissue engineering.

Regeneration of nerve tissue is a challenging issue in regenerative medicine. Especially, the peripheral nerve defects related to the accidents are one of the leading health problems. For large degeneration of peripheral nerve, nerve grafts are used in order to obtain a connection. These grafts should be biodegradable to prevent second surgical intervention. In order to make more effective nerve tissue engineering materials, nanotechnological improvements were used. Especially, the addition of electrically conductive and biocompatible metallic particles and carbon structures has essential roles in the stimulation of nerves. However, the metabolizing of these structures remains to wonder because of their nondegradable nature. In this study, biodegradable and conductive nerve tissue engineering materials containing zero-valent iron (Fe) nanoparticles were developed and investigated under in vitro conditions. By using electrospinning technique, fibrous mats composed of electrospun poly(ε-caprolactone) (PCL) nanofibers and Fe nanoparticles were obtained. Both electrical conductivity and mechanical properties increased compared with control group that does not contain nanoparticles. Conductivity of PCL/Fe5 and PCL/Fe10 increased to 0.0041 and 0.0152 from 0.0013 Scm-1 , respectively. Cytotoxicity results indicated toxicity for composite mat containing 20% Fe nanoparticles (PCL/Fe20). SH-SY5Y cells were grown on PCL/Fe10 best, which contains 10% Fe nanoparticles. Beta III tubulin staining of dorsal root ganglion neurons seeded on mats revealed higher cell number on PCL/Fe10. This study demonstrated the impact of zero-valent Fe nanoparticles on nerve regeneration. The results showed the efficacy of the conductive nanoparticles, and the amount in the composition has essential roles in the promotion of the neurites.

Process optimisation, biocompatibility and anti-cancer efficacy of curcumin loaded gelatine microparticles cross-linked with dialdeyhde carboxymethyl cellulose.

In this study, we produced curcumin loaded gelatine microparticles, through spray-drying method, with dialdehyde carboxymethyl cellulose (DCMC) which is introduced as a new cross-linking agent for drug delivery systems and examined toxicities by comparison of traditional cross-linking agents. We employed various parameters in the production and tried to develop the most efficient drug delivery system through Taguchi method by examining efficiencies on gastric cancer under in vitro conditions. The results indicated gelatine microparticles cross-linked with DCMC offers more biocompatible drug delivery systems. The particle size of the microparticles produced via different parameters varies from 1.926 to 3.357 µm. Curcumin was substantially remained stable after 6 months. This study indicates potential use of DCMC cross-linked gelatine microparticles as drug delivery vehicle.

Polypropylene composite hernia mesh with anti-adhesion layer composed of polycaprolactone and oxidized regenerated cellulose.

Hernia surgeries are at the top of the general surgery operations. However, visceral adhesion, which is one of the worst complications of these operations, is still a major problem. One of the most preferred methods to prevent adhesion is the use of biomaterials. Polypropylene (PP) mesh is frequently preferred product in clinical applications owing to its mechanically robust structure against deformation within the body. However, PP meshes do not have anti-adhesive properties. Oxidized regenerated cellulose (ORC), on the other hand, is one of the most preferred products in preventing the adhesion in clinical use. ORC is not easily processable due to solubility limitations; and it must be used externally. In this study, for the first time, we designed a composite mesh structure with ORC and produced an antibacterial and anti-adhesive double-sided mesh by electro-spinning ORC micro-particles with poly(ε­caprolactone) (PCL) on PP mesh to form a composite structure. We conducted in vitro cell culture studies to determine bio-compatibility performances. We evaluated the anti-adhesion and comprehensive bio-compatibility studies through in vivo experiments. The results revealed that ORC presence and optimization of ORC degradation by coating with PCL play an important role in adhesion prevention and introduced a product prototype with efficient anti-adhesion properties.

A Polypropylene-Integrated Bilayer Composite Mesh with Bactericidal and Antiadhesive Efficiency for Hernia Operations.

Polypropylene (PP) mesh has been widely used in hernia fixation operations for more than one hundred years, and peritoneal adhesion is still one of the main complications after hernia fixation operations. For preventing peritoneal adhesion, many solutions have been offered, including gel systems, adhesion barrier membranes, and bilayer meshes. Among these, bilayer meshes come to the forefront as they serve for both hernia repair and adhesion prevention. In this study, we developed an easy and effective method to produce a multifunctional PP-integrated bilayer mesh composed of poly(lactic-co-glycolic acid) and chitosan with no need for neutralization. We made the composite mesh by electrospinning a layer onto the PP mesh. We evaluated the material characteristics, in vitro bactericidal activities, and interactions between the cells and materials. Then, we conducted in vivo efficiency studies. The results proved that the PP-integrated bilayer composite mesh is bactericidal against Escherichia coli and Staphylococcus aureus, is tissue-compatible, and supremely prevents adhesion.

Zero valent zinc nanoparticles promote neuroglial cell proliferation: A biodegradable and conductive filler candidate for nerve regeneration.

Regeneration of nerve, which has limited ability to undergo self-healing, is one of the most challenging areas in the field of tissue engineering. Regarding materials used in neuroregeneration, there is a recent trend toward electrically conductive materials. It has been emphasized that the capacity of conductive materials to regenerate such tissue having limited self-healing ability improves their clinical utility. However, there have been concerns about the safety of materials or fillers used for conductance due to their lack of degradability. Here, we attempt to use poly(Ɛ-caprolactone) (PCL) matrix consisting of varying proportions of zero valent zinc nanoparticles (Zn NPs) via electrospinning. These conductive, biodegradable, and bioactive materials efficiently promoted neuroglial cell proliferation depending on the amount of Zn NPs present in the PCL matrix. Chemical characterizations indicated that the incorporated Zn NPs do not interact with the PCL matrix chemically and that the Zn NPs improved the tensile properties of the PCL matrix. All composites exhibited linear conductivity under in vitro conditions. In vitro cell culture studies were performed to determine the cytotoxicity and proliferative efficiency of materials containing different proportions of Zn NPs. The results were obtained to explore new conductive fillers that can promote tissue regeneration.