Diagnostic and prognostic utility of TROP-2, SLP-2, and CXCL12 expression in papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most frequent thyroid malignancy. Histopathological examination is widely accepted as the gold standard test for the diagnosis of PTC. However, the histopathological examination sometimes can't differentiate PTC from other thyroid diseases. Differentiating PTC from other thyroid diseases is essential for a therapeutic approach and prognosis. OBJECTIVES: The current study was performed to investigate the utility of TROP-2, SPL-2, and CXCL12 mRNA and protein expression in discriminating PTC from other thyroid diseases that mimic PTC. METHODS: The current study was performed on 75 cases of surgically resected thyroid glands. The cases were distributed in two groups: the PTC group and the non-PTC group. The PTC group consisted of 35 cases (25 patients of the classic PTC variant and 10 patients of the PTC follicular variant). The non-PTC group consisted of 40 cases (10 cases were multinodular goiter, 5 cases were Graves' disease, 5 cases were Hashimoto thyroiditis, 15 patients were follicular adenoma (FA) and 5 cases were follicular carcinoma). TROP-2, SPL-2, and CXCL12 mRNA expression were estimated by qRT-PCR, and protein expression was estimated by immunohistochemistry. RESULTS: There were upregulated TROP-2, SPL-2, and CXCL12 mRNA and protein expressions in PTC compared to non-PTC (P< 0.001, for each). There was a statistically significant upregulation in the mRNA expression of the three genes among PTC cases with larger tumor sizes (P< 0.001, for each), those with tumor stages III and IV (P= 0.008, 0.002 and < 0.001 respectively), and those with LN metastasis (P< 0.001, for each). Moreover, there was a statistically significant upregulation in CXCL-12 gene expression among PTC cases with extra-thyroid extension (P< 0.001). CONCLUSION: mRNA expression of TROP-2, SPL-2, and CXCL12 among PTC cases increased in larger tumor size, tumor stages III and IV, and LN metastasis. Moreover, there was an increase in CXCL-12 gene expression among PTC cases with extra-thyroid extension. Thus, TROP-2, SPL-2, and CXCL12 expressions could be possible diagnostic and prognostic markers in PTC.

Mechanistic-Based Classification of Endocytosis-Related Inhibitors: Does It Aid in Assigning Drugs against SARS-CoV-2?

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) canonically utilizes clathrin-mediated endocytosis (CME) and several other endocytic mechanisms to invade airway epithelial cells. Endocytic inhibitors, particularly those targeting CME-related proteins, have been identified as promising antiviral drugs. Currently, these inhibitors are ambiguously classified as chemical, pharmaceutical, or natural inhibitors. However, their varying mechanisms may suggest a more realistic classification system. Herein, we present a new mechanistic-based classification of endocytosis inhibitors, in which they are segregated among four distinct classes including: (i) inhibitors that disrupt endocytosis-related protein-protein interactions, and assembly or dissociation of complexes; (ii) inhibitors of large dynamin GTPase and/or kinase/phosphatase activities associated with endocytosis; (iii) inhibitors that modulate the structure of subcellular components, especially the plasma membrane, and actin; and (iv) inhibitors that cause physiological or metabolic alterations in the endocytosis niche. Excluding antiviral drugs designed to halt SARS-CoV-2 replication, other drugs, either FDA-approved or suggested through basic research, could be systematically assigned to one of these classes. We observed that many anti-SARS-CoV-2 drugs could be included either in class III or IV as they interfere with the structural or physiological integrity of subcellular components, respectively. This perspective may contribute to our understanding of the relative efficacy of endocytosis-related inhibitors and support the optimization of their individual or combined antiviral potential against SARS-CoV-2. However, their selectivity, combined effects, and possible interactions with non-endocytic cellular targets need more clarification.

Chitosan and Nano-Chitosan for Management of Harpophora maydis: Approaches for Investigating Antifungal Activity, Pathogenicity, Maize-Resistant Lines, and Molecular Diagnosis of Plant Infection.

The rapid spread of late wilt disease among maize cultivations has resulted in serious economic losses in many countries. Harpophora maydis is the main cause of this destructive vascular disease. Here we evaluate the fungicidal activity of chitosan and nano-chitosan against six aggressive isolates of H. maydis collected from different Egyptian governorates. Pathogenicity tests for these isolates show that the highest disease severity was found for the Giza isolate. The isolates were tested for their response to the fungicide Permis, chitosan, and nano-chitosan treatments in vitro and in vivo. Nano-chitosan treatments fully inhibited the radial growth of H. maydis isolates at concentrations of 5 and 10 mM, compared to the full control growth (9 cm in diameter). On the other hand, in vitro, in vivo, and molecular diagnosis results showed high antifungal activity of chitosan and nano-chitosan compared to the Permis fungicide. Chitosan at the nano and normal scales proved a potent ability to enhance plant resistance in response to H. maydis. Disease severity (DS%) was extremely decreased among the tested cultivars by using nano-chitosan; the highest percentage was obtained on Giza 178 cv, where the DS% was 21.7% compared to 42.3% for the control. Meanwhile, the lowest percentage was obtained on Giza 180 cv with DS% 31.2 and the control with 41.3%. The plants treated with nano-chitosan showed the highest growth parameters for all cultivars. Such natural treatments could reduce the impact on the environment as they are non-pollutant natural compounds, protect the plants by reducing fungal activity, and induce plant resistance.