We aimed to assess the utility of quantitative analysis of AgNORs and Ki67 labeling index (LI) in the differential diagnosis of different thyroid lesions. This study included: 25 papillary carcinomas, 7 follicular carcinomas, 21 follicular adenomas and 27 nodular goiters. Using a semiautomatic image analysis system, Ag NORs parameters were measured and calculated including: total area of AgNORs, mean Ag NOR number in nuclei, nuclear area, mean area of AgNOR dots per each nucleus, number of central and marginal AgNOR dots, and the relative ratio of total area of AgNOR dots/total area of nucleus. Ki67 immunostaining was performed and the LI was determined. There was a significant difference between groups of thyroid lesions regarding total area of AgNORs, Ag NOR number and number of marginal Ag NOR dots. According to receiver operating characteristic curve, Ag NORs number =2.91 and marginal Ag NORs = 2.67 were useful cut off values above which follicular carcinoma can be diagnosed with 100 % sensitivity, 79 % specificity, 76 % PPV, 100 % NPV and 85 % diagnostic accuracy for both parameters. Mean Ki67 LI in our study was 14.12 ± 2.29, 61.42 ± 3.77, 34.90 ± 3.49 and 18.60 ± 1.96 for papillary carcinoma, follicular carcinoma, follicular adenoma and nodular goiter respectively. Ki67 LI showed statistically significant difference between follicular carcinoma and follicular adenoma (p = 0.026) and between papillary carcinoma and follicular adenoma (p = 0.007). Quantification of Ag NORs and Ki67 LI could be used as helpful ancillary methods in the differentiation between different thyroid lesions.

Schizophrenia remains one of the most chronic and highly disabling mental disorders. Lumateperone is a recent FDA-approved atypical antipsychotic drug for the treatment of schizophrenia. However, the internal FDA pathologist raised concerns regarding pigment deposition associated with degeneration in different tissue in animal studies with lumateperone treatment. The adrenal gland may be implicated in lumateperone side effects, and quercetin may have the ability to fulfill this treatment gap. To prove this hypothesis, 40 male guinea pigs were used and divided into four groups; control, quercetin-treated, lumateperone-treated, and quercetin/lumateperone cotreated orally for 28 consecutive days. Behavioral forced swim (FST) and open field (OF) tests were done at the end of treatment. Retro-orbital blood samples were taken to assess hormones: adrenocorticotropic hormone (ACTH), cortisol, dehydroepiandrosterone acetate (DHEA), and aldosterone, along with an assessment of oxidative stress parameters: malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Adrenal glands were extracted for histopathological assessment with H&E, Mallory trichome staining, immunostaining, and electron microscopy studies. Lumateperone-treated group showed a significant reduction in the activity in FST and OF with histopathological deterioration in adrenal secretory function and structure and increased expression of interleukin-6 (IL-6), CASPASE-3, collagen deposition, and decreased proliferating cell nuclear antigen (PCNA). Cytoplasmic vacuolation, pyknosis of the nuclei, increase in the lysosome, lipofuscin pigment, and cellular infiltration with diminishing in the number of secretory granules could all be observed in lumateperone-treated group. Coadministration of quercetin and lumateperone showed improvement of the previously deteriorated parameters. Quercetin had a prophylactic effect against lumateperone depressive-like effect on animal behavior and its possible adrenal damage.Graphical AbstractConceptual framework for the proposed mechanism of action of coadministration of quercetin and lumateperone.

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Background: Remdesivir is a novel broad spectrum antiviral drug previously used to treat Ebola. It is a pro-drug nucleoside with antiviral activity that is opposed to SARS-CoV-2 and coronavirus. Aim: Current research was planned to evaluate and compare the potential ameliorative impact of the hematopoietic-stem-cell mobilized by the granulocyte colony-stimulating factor (G-CSF) versus BM-MSC on the effect of novel antiviral remdesivir on the kidney. Materials and Methods: Rats divided into four groups: control group, Remdesivir treated group (20 mg/kg/day IV on the first day followed by 10 mg/kg/day for 6 days), Remdesivir + BM-MSCs group (3x10⁶ cells/ml of PKH26 labelled MSC) and Remedesivir+ Filgrastim group (70 μg/kg/day/5 days). At the end of the experiment, animals were anaesthetized and sacrificed. Both animal kidneys were excised for histological, immunohistochemistry, and electron microscopy studies. Biochemical and morphometric assessments had been performed. Results: Remdesivir caused distortion and degeneration of both the glomeruli and the renal tubules associated with Bowman's space widening. It greatly increased the deposition of collagen and enhanced the expression of caspase 3, IL-6, and TGF-β1. Ultrastructure changes were observed in the form of thickening of glomerular basement membrane, dilated basal plasma membrane infoldings of tubular epithelium and mitochondrial degeneration. Biochemically, decreased antioxidant enzymes, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) with increased serum urea and creatinine were also recorded. Both BM-MSCs and G-CSF improved histological structure and function of the kidney. Conclusion:Prescribing drugs such as remdesivir should be carried out with severe care. BM-MSCs and G-CSF are an efficient and ideal option to protect patients from irreversible kidney damage.

Background: Cyclophosphamide is a chemotherapeutic agent used for treatment of leukemia, lymphoma and myeloma. Several studies reported wide range of cyclophosphamide induced cardiotoxicity in cancerous patients. Alpha lipoic acid is a natural antioxidant used widely for prevention and treatment of different conditions. Aim of the work: This work was conducted to study the role of alpha lipoic acid in cyclophosphamide induced cardiotoxicity basing on histological and ultrastructural studies. Material and Methods: Forty-four adult male Albino rats were divided into four groups: group I (control), group II (alpha lipoic acid-treated) in a dose (25 mg/kg body weight/day) given orally, group III (cyclophosphamide-treated) in a dose (200 mg/kg body weight) single dose injected intraperitoneally and group IV (alpha lipoic acid plus cyclophosphamid-treated). The experiment was conducted for ten days. Cardiac muscle specimens were subjected to light, electron microscopic and immunohistochemical study. Results: Microscopic examination of cardiac muscle of cyclophosphamide treated group (III) showed focal disruption and vacuolation of cardiac muscle fibers with mononuclear infiltration between cardiac muscle fibers. Ultrastructurally, destruction of myofibrils, swollen, irregular arranged mitochondria and dilated SER were noted. Some nuclei showed chromatolysis and others were heterochromatic with irregular nuclear membrane. These results were confirmed by significant decrease in Bcl2. The intercellular spaces were wide contained dilated congested blood vessels and collagen. Alpha lipoic acid administration improved cardiac muscle architecture but still not attained the complete normal morphology Conclusion: Supplementation of alpha lipoic acid in concomitant with cyclophosphamide (CYP) can ameliorate the CYP induced cardiac injury.