Antioxidant effects of a novel pioglitazone analogue (PA9) in a rat model of diabetes: Modulation of redox homeostasis and preservation of tissue architecture.

Oxygen-free radicals have been implicated in the initiation of diabetic complications. Thiazolidinediones (TZDs), known for their antidiabetic properties, also demonstrate notable antioxidant and anti-inflammatory effects. Although a recently developed imidazolyl analogue of pioglitazone (PA9) has exhibited superior glucose-lowering efficacy compared to pioglitazone, its antioxidant effects remain unexplored. Thus, the objective of this study is to evaluate the antioxidant properties of PA9 in animal models with diabetes. Rats were randomly separated into the following four groups: control, diabetic, and two groups treated orally with pioglitazone as a standard drug and PA9 for ten days. Upon completion of the experiment, tissues from the liver, heart, brain, pancreas, spleen, and kidneys were collected to assess oxidant/antioxidant markers and histological alterations. The administration of PA9 resulted in a noteworthy reduction in malondialdehyde (MDA) levels compared to the diabetic group (p < 0.05). The group receiving PA9 displayed elevated levels of three antioxidant markers, catalase (CAT), superoxide dismutase (SOD), and total thiol, in pancreatic tissue compared to diabetic rats (p < 0.05). Furthermore, increased content of CAT was evident in the heart (p < 0.05), spleen (p < 0.001), brain, and kidney tissues in the PA9-treated group, along with augmented thiol content in the spleen compared to the diabetic group. Remarkably, no significant histological changes were observed in the liver, pancreas, heart, brain, spleen, and kidneys of the PA9-treated groups relative to diabetic rats. PA9 effectively mitigates oxidative stress, modulates redox homeostasis, and shows promise in preventing diabetic complications. The proven safety profile of this analogue underscores its potential, warranting comprehensive clinical evaluation to thoroughly understand its therapeutic scope and efficacy in the management of diabetes.

Comparison of FNA-based conventional cytology specimens and digital image analysis in assessment of pancreatic lesions.

Objectives: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is one of the most important diagnostic tools for investigation of suspected pancreatic masses, although the interpretation of the results is controversial. In recent decades, digital image analysis (DIA) has been considered in pathology. The aim of this study was to assess the DIA in the evaluation of EUS-FNA based cytopathological specimens of pancreatic masses and comparing it with conventional cytology analysis by pathologist. Material and Methods: This study was performed using cytological slides related to EUS-FNA samples of pancreatic lesions. The digital images were prepared and then analyzed by ImageJ software. Factors such as perimeter, circularity, area, minimum, maximum, mean, median of gray value, and integrated chromatin density of cell nucleus were extracted by software ImageJ and sensitivity, specificity, and cutoff point were evaluated in the diagnosis of malignant and benign lesions. Results: In this retrospective study, 115 cytology samples were examined. Each specimen was reviewed by a pathologist and 150 images were prepared from the benign and malignant lesions and then analyzed by ImageJ software and a cut point was established by SPSS 26. The cutoff points for perimeter, integrated density, and the sum of three factors of perimeter, integrated density, and circularity to differentiate between malignant and benign lesions were reported to be 204.56, 131953, and 24643077, respectively. At this cutting point, the accuracy of estimation is based on the factors of perimeter, integrated density, and the sum of the three factors of perimeter, integrated density, and circularity were 92%, 92%, and 94%, respectively. Conclusion: The results of this study showed that digital analysis of images has a high accuracy in diagnosing malignant and benign lesions in the cytology of EUS-FNA in patients with suspected pancreatic malignancy and by obtaining cutoff points by software output factors; digital imaging can be used to differentiate between benign and malignant pancreatic tumors.

Adipose-derived human mesenchymal stem cells seeded on denuded or stromal sides of the amniotic membrane improve angiogenesis and collagen remodeling and accelerate healing of the full-thickness wound.

Several strategies have been proposed to enhance wound healing results. Along with other forms of wound dressing, the human amniotic membrane (HAM) has long been regarded as a biological wound dressing that decreases infection and enhances healing. This study investigates the feasibility and effectiveness of wound healing using decellularized HAM (dAM) and stromal HAM (sAM) in combination with adipose-derived human mesenchymal stem cells (AdMSCs). The dAM and sAM sides of HAM were employed as wound dressing scaffolds, and AdMSCs were seeded on top of either dAM or sAM. Sixty healthy Wistar rats were randomly divided into three groups: untreated wound, dAM/AdMSCs group, and sAM/AdMSCs group. The gene expression of VEGF and COL-I was measured in vitro. Wound healing was examined after wounding on days 3, 7, 14, and 21. The expression level of VEGF was significantly higher in sAM/AdMSCs than dAM/AdMSCs (P ≤ 0.05), but there was no significant difference in COL-I expression (P ≥ 0.05). In vivo research revealed that on day 14, wounds treated with sAM/AdMSCs had more vascularization than wounds treated with dAM/AdMSCs (P ≤ 0.01) and untreated wound groups on days 7 (P ≤ 0.05) and 14 (P ≤ 0.0001), respectively. On days 14 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), and 21 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), the collagen deposition in the wound bed was significantly thicker in the sAM/AdMSCs and dAM/AdMSCs groups compared to untreated wounds. The study demonstrated that the combination of sAM and AdMSCs promotes wound healing by enhancing angiogenesis and collagen remodeling.

Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumor with Leptomeningeal Seeding: Case Report and Literature Review.

Spinal intradural primary malignant peripheral nerve sheath tumors (MPNST) are rare in patients without neurofibromatosis. Here we represent a 3-year-old girl of primary intradural spinal malignant peripheral nerve sheath tumor. The tumor was removed partially and MPNST was diagnosed in the histopathological examination. Her condition deteriorated due to acute hydrocephalus in the following days. In this article, we discuss the clinical presentation, imaging, treatment, and prognosis of our patient and the other 22 patients of primary intradural MPNST, found in the literature. The Kaplan?Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. This analysis showed that age, was an important factor predicting short-term survival of patients with MPNST.

Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors.

BACKGROUND: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors. MATERIALS AND METHODS: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels. RESULTS: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes. CONCLUSION: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.