Targeting the PANoptosome with 3,4-Methylenedioxy-ß-Nitrostyrene, Reduces PANoptosis and Protects the Kidney against Renal Ischemia-Reperfusion Injury.

OBJECTIVES: The objectives of this study were a) to investigate the effect of targeting the PANoptosome with 3,4-methylenedioxy-ß-nitrostyrene (MNS) on PANoptosis in the Renal ischemia-reperfussion (RIR) model b) to investigate the kidney protective effect of MNS toward RIR injury. METHODS: Thirty-two rats were divided into four groups randomly. The groups were assigned as Control, Sham, DMSO (dimethyl sulfoxide) and MNS groups. The rats in the MNS group were intraperitoneally given 20 mg/kg of MNS 30 minutes before reperfusion. 2% DMSO solvent that dissolves MNS were given to the rats in DMSO group. Left nephrectomy was performed on the rats under anesthesia at the 6th hour after reperfusion. Glutathione peroxidase (GPx), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and 8-Okso-2'-deoksiguanozin (8-OHdG) levels were measured. Immunohistochemical analysis, electron microscopic and histological examinations were carried out in the tissues. RESULTS: Total tubular injury score was lower in the MNS group (p < 0.001). Caspase-3, Gasdermin D and MLK (Mixed Lineage Kinase Domain Like Pseudokinase) expressions were considerably decreased in the MNS group (p < 0.001). Apoptotic index (AI) was found to be low in the MNS group (p < 0.001). CAT and SOD levels were higher in the MNS Group (p = 0.006, p = 0.0004, respectively). GPx, MDA, and 8-OH-dG levels were similar (p > 0.05) in all groups. MNS considerably improved the tissue structure, based on the electron microscopic analysis. CONCLUSIONS: Our results suggested that MNS administrated before the reperfusion reduces pyroptosis, apoptosis and necroptosis. These findings suggest that MNS significantly protects the kidney against RIR injury by reducing PANoptosis as a result of specific inhibition of Nod-like receptor pyrin domain-containing 3 (NLRP 3), one of the PANoptosome proteins.

Differentiation of skin biopsies by light scattering spectroscopy.

INTRODUCTION: Spectroscopic systems are medical tools that are used for the detection of cancerous tissues ex vivo and in vivo. AIM: To differentiate inflammatory and benign skin lesions of excised biopsy samples via a combination of multivariate statistical analysis. MATERIAL AND METHODS: Spectral data were obtained from a total of 22 inflammatory and ten benign skin biopsy samples from 30 patients in the visible wavelength (450-750 nm) regions. Spectral data were compared with the dermatopathology results. Spectral data analyses of biopsy samples were performed via principal component analysis (PCA), followed by linear discriminant analysis (LDA). The differentiation performance was calculated with the receiver operating characteristic (ROC) curve analysis. RESULTS: The classification based on the discriminant function score provided a sensitivity of 90.9% and a specificity of 80% in discriminating benign from inflammatory lesions with an accuracy of 87.5%. CONCLUSIONS: Our study revealed that light scattering spectroscopy could discriminate between inflammatory and benign skin lesions of excised biopsy samples with high sensitivity by using multivariate statistical analysis. It can be concluded that the high diagnostic accuracy of the optical spectroscopy method has the potential to use as a supplementary system to distinguish inflammatory skin lesions from benign during the pathological examination.