Evaluating the docetaxel effect in an animal model of polyarthritis.

Rheumatoid arthritis (RA) is immune-mediated, inflammatory disease that affects synovial joints, and characterized by inflammatory changes in synovial tissue, cartilage, bone, and less commonly in extra-articular structures. Docetaxel (DTX) is a semi-synthetic anti-neoplastic medication. Peptidyl-arginine deiminase type 4 (PAD4) is expressed in macrophages and neutrophils in RA synovial membrane. Their effectiveness is in producing anti-cyclic citrullinated peptide antibodies (ACPA)-targeted citrullinated neoepitopes. AIM: To evaluate the anti-inflammatory effects of DTX in RA and the effect of methotrexate on PAD4 to investigate its potential as an RA biomarker. METHODS: Forty male Wistar rats were divided into five groups of eight rats. Healthy rats formed the control group. The Second Group to Fifth group were induced with Complete Freund's adjuvant. The third group received DTX at a dosage of 1 mg/kg on alternate days, as determined by a preliminary experiment. The fourth group was given 1 mg/kg/week of methotrexate intraperitoneally. The fifth group was treated with a half dose of DTX and methotrexate simultaneously. RESULTS: Significant Arthritis index and knee joint circumference decrease in the DTX group. No significant difference in body weight, platelet-lymphocyte ratio, and white blood cell count between the groups. Neutrophile lymphocyte ratio showed weak correlation with ACPA, while PAD4 showed good correlation with RA markers. Level of ACPA, PAD4, TNF-α, IL-1ß, and VEGF significantly decreased in the DTX group than induction group (p < 0.05). CONCLUSION: DTX reduces the progression and joint destruction in rats induced by Complete Freund's Adjuvant which may due to inhibition of PAD4, TNF-α, IL-1ß, VEGF, and ACPA. Also, methotrexate exhibited anti PAD4 effect.

SIRT1720 promotes survival of corneal epithelial cells via the P53 pathway.

PURPOSE: To investigate the protective role of SRT1720 (SIRT1 activator) against the oxidative stress caused by H2O2 in the corneal cell line. METHODS: Human corneal (2.040 pRSV-T) cell lines were cultured and treated with SRT1720 (as SIRT1 activator) and nicotinamide (NAM, a SIRT1 inhibitor), and incubated with H2O2. The expression level of SIRT1, p53, and acetyl-p53 was measured by western blot. Propidium iodine/annexin V-FITC staining, and flow cytometry was used to evaluate apoptosis. The trypan blue assay was used to assess the morphological modifications that occurred after the treatment, and Pifithrin-α (PFT-α) was used to inhibit the p53 pathway. RESULTS: The investigation revealed that under oxidative stress, SRT1720 caused a reduction in acetyl-p53 expression and increased SIRT1 expression. It was also found that under oxidative stress, SRT1720 suppressed apoptosis. In comparison, NAM promoted cell apoptosis under oxidative stress. NAM's destructive effect was eliminated by PFT-α, a suppressor of the p53 pathway. PFT-α reduced the morphological changes in 2.040 pRSV-T cell lines compared to NAM treatment and inhibited apoptosis. CONCLUSIONS: The protective effects of the SIRT1 activator (SRT1720) indicate that H2O2 induces oxidative stress-associated cell damage. The results also encouraged us to consider using SRT1720 to improve corneal safety and reduce the adverse effects of oxidative damage.

YKL-40 as a novel diagnostic biomarker in Toxoplasmosis.

Toxoplasmosis is one of the most globally prevalent zoonotic infection caused by an obligate, intracellular parasite called Toxoplasma gondii. Toxoplasmosis actively triggers an acute immune response and inflammatory reactions, which causes serious pathological changes in various tissues in the human body, and more evidently localizes in different nervous tissues of various body organs. The YKL-40 is a glycoprotein secreted by numerous cell types in different patterns associated with various pathological processes such as inflammatory reactions, tissue remodeling, and fibrosis, and is a disease-specific biomarker of neuroinflammation. Therefore, this study aimed to determine whether the YKL-40 is markedly increased in toxoplasmosis or not and whether its level is different between the acute and chronic phases of the infection to determine if it can be used as a clinically useful biomarker in the diagnosis, and determination of disease severity and follow-up of toxoplasmosis. Accordingly, a total of 80 serum samples were collected from previously diagnosed female patients of different ages with toxoplasmosis. In addition, serum samples of 10 healthy females were used as the control. Patients were first divided into two groups (30 patients with acute infection, and 50 patients with chronic infection) depending on the results of detection of specific anti-Toxoplasma IgM and IgG by enzyme-linked immunosorbent assay (ELISA). The level of YKL-40 was then measured in the patients' serum by ELISA. The statistical analysis of data clearly disclosed very highly significant differences (P < 0.001) between the level of YKL-40 in the acute infection group and healthy controls, chronic infection group and healthy controls, and between the groups with acute and chronic infections. These findings led to conclude that YKL-40 classify as a unique and sophisticated biomarker in the diagnosis of toxoplasmosis where it can vitally be used to detect the stage of the disease, whether acute or chronic, besides its ability to detect the infection.