A morphometric study of human submandibular gland in type 2 diabetic status

Diabetes Mellitus Type 2 represents one of the principal diseases that afflict the world population. It is well documented that diabetes affects both morphology and function of several organs. In diabetic rats significant structural changes have been demonstrated in salivary glands, such as accumulation of secretory material and lipid droplets within secretory cells, parenchymal degeneration and its replacement with fibrous connective tissue (1). With regard to human salivary glands, the data are scanty and conflicting. Our work, carried out by light and electron microscopy, is based on the evaluation of the morphological changes which occur in human submandibular glands of diabetic with respect to non diabetic patients. Surgical fragments of glandular tissue were fixed, dehydrated, and processed for light and electron microscopy. Randomly chosen images were analyzed with Image Pro Plus software to record the dimension of acini, serous cells, secretory granules and other variables. Data were analyzed by Student’s t-test and Mann Whitney test. In diabetic glands statistically significant morphological changes were observed, such as enlargement of serous acini and increase of secretory granules area. These results suggest that the secretory activity of human submandibular gland is severely affected by the diabetic status. Obviously these data need to be confirmed with further measurements in order to explain better how diabetes affects human salivary glands

Ultrastructural evidence of a secretory role for melatonin in the human parotid gland

In vivo animal studies show that pentagastrin, cholecystokinin and melatonin cause the secretion and synthesis of salivary proteins. Melatonin occurs in large amounts in the gut and is released into the blood on food intake. In vitro experiments suggest that pentagastrin exerts secretory activity in human salivary glands, as judged by ultrastructural changes, reflecting secretion, and an actual protein output. Currently, it is hypothesised that melatonin induces secretory exocytotic events in the human parotid gland. Human parotid tissues were exposed to a high single concentration of melatonin in vitro, processed for high resolution scanning electron microscopy and then assessed morphometrically with the emphasis on the membrane of the intercellular canaliculi, a site of protein secretion. Compared with controls and in terms of density, the melatonin-exposed parotid tissues displayed increases in protrusions (signalling anchored granules) and microbuds (signalling membrane recycling and/or vesicle secretion) and decreases in microvilli (signalling cytoskeletal re-arrangement related to exocytosis), phenomena abolished or very largely reduced by the melatonin receptor blocker, luzindole. In conclusion, acinar serous cells of parotid tissue displayed in vitro exocytotic activity to melatonin, signalling protein secretion. Whether, under physiological conditions, melatonin influences the secretion of human parotid glands remains to be explored, however

A morphometric study of human submandibular gland in type 2 diabetic status

Diabetes Mellitus Type 2 represents one of the principal diseases that afflict the world population. It is well documented that diabetes affects both morphology and function of several organs. In diabetic rats significant structural changes have been demonstrated in salivary glands, such as accumulation of secretory material and lipid droplets within secretory cells, parenchymal degeneration and its replacement with fibrous connective tissue (1). With regard to human salivary glands, the data are scanty and conflicting. Our work, carried out by light and electron microscopy, is based on the evaluation of the morphological changes which occur in human submandibular glands of diabetic with respect to non diabetic patients. Surgical fragments of glandular tissue were fixed, dehydrated, and processed for light and electron microscopy. Randomly chosen images were analyzed with Image Pro Plus software to record the dimension of acini, serous cells, secretory granules and other variables. Data were analyzed by Student’s t-test and Mann Whitney test. In diabetic glands statistically significant morphological changes were observed, such as enlargement of serous acini and increase of secretory granules area. These results suggest that the secretory activity of human submandibular gland is severely affected by the diabetic status. Obviously these data need to be confirmed with further measurements in order to explain better how diabetes affects human salivary glands. Maria Alberta Lilliu gratefully acknowledges Sardinia Regional Government for the financial support of her PhD scholarship (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007-2013 - Axis IV Human Resources, Objective l.3, Line of Activity l.3.1.). Michela Isola gratefully acknowledges Sardinia Regional Government for the financial support (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007-2013 - Axis IV Human Resources, Objective l.3, Line of Activity l.3.1 “Avviso di chiamata per il finanziamento di Assegni di Ricerca”)

4-(3-Phenyl-4-(3,4,5-trimethoxybenzoyl)-1H-pyrrol-1-yl)benzenesulfonamide, a Novel Carbonic Anhydrase and Wnt/β-Catenin Signaling Pathway Dual-Targeting Inhibitor with Potent Activity against Multidrug Resistant Cancer Cells

We synthesized new pyrrole and indole derivatives as human carbonic anhydrase (hCA) inhibitors with the potential to inhibit the Wnt/β-catenin signaling pathway. The presence of both N1-(4-sulfonamidophenyl) and 3-(3,4,5-trimethoxyphenyl) substituents was essential for strong hCA inhibitors. The most potent hCA XII inhibitor 15 (Ki = 6.8 nM) suppressed the Wnt/β-catenin signaling pathway and its target genes MYC, Fgf20, and Sall4 and exhibited the typical markers of apoptosis, cleaved poly(ADP-ribose)polymerase, and cleaved caspase-3. Compound 15 showed strong inhibition of viability in a panel of cancer cells, including colorectal cancer and triple-negative breast cancer cells, was effective against the NCI/ADR-RES DOX-resistant cell line, and restored the sensitivity to doxorubicin (DOX) in HT29/DX and MDCK/P-gp cells. Compound 15 is a novel dual-targeting compound with activity against hCA and Wnt/β-catenin. It thus has a broad targeting spectrum and is an anticancer agent with specific potential in P-glycoprotein overexpressing cell lines

Targeting CBP and p300: Emerging Anticancer Agents

CBP and p300 are versatile transcriptional co-activators that play essential roles in regulating a wide range of signaling pathways, including Wnt/β-catenin, p53, and HIF-1α. These co-activators influence various cellular processes such as proliferation, differentiation, apoptosis, and response to hypoxia, making them pivotal in normal physiology and disease progression. The Wnt/β-catenin signaling pathway, in particular, is crucial for cellular proliferation, differentiation, tissue homeostasis, and embryogenesis. Aberrant activation of this pathway is often associated with several types of cancer, such as colorectal tumor, prostate cancer, pancreatic and hepatocellular carcinomas. In recent years, significant efforts have been directed toward identifying and developing small molecules as novel anticancer agents capable of specifically inhibiting the interaction between β-catenin and the transcriptional co-activators CBP and p300, which are required for Wnt target gene expression and are consequently involved in the regulation of tumor cell proliferation, migration, and invasion. This review summarizes the most significant and original research articles published from 2010 to date, found by means of a PubMed search, highlighting recent advancements in developing both specific and non-specific inhibitors of CBP/β-catenin and p300/β-catenin interactions. For a more comprehensive view, we have also explored the therapeutic potential of CBP/p300 bromodomain and histone acetyltransferase inhibitors in disrupting the transcriptional activation of genes involved in various signaling pathways related to cancer progression. By focusing on these therapeutic strategies, this review aims to offer a detailed overview of recent approaches in cancer treatment that selectively target CBP and p300, with particular emphasis on their roles in Wnt/β-catenin-driven oncogenesis

Metabolic Rewiring in Cancer: Small Molecule Inhibitors in Colorectal Cancer Therapy

Alterations in cellular metabolism, such as dysregulation in glycolysis, lipid metabolism, and glutaminolysis in response to hypoxic and low-nutrient conditions within the tumor microenvironment, are well-recognized hallmarks of cancer. Therefore, understanding the interplay between aerobic glycolysis, lipid metabolism, and glutaminolysis is crucial for developing effective metabolism-based therapies for cancer, particularly in the context of colorectal cancer (CRC). In this regard, the present review explores the complex field of metabolic reprogramming in tumorigenesis and progression, providing insights into the current landscape of small molecule inhibitors targeting tumorigenic metabolic pathways and their implications for CRC treatment

Emerging Therapeutic Agents for Colorectal Cancer

There are promising new therapeutic agents for CRC patients, including novel small-molecule inhibitors and immune checkpoint blockers. We focused on emerging CRC’s therapeutic agents that have shown the potential for progress in clinical practice. This review provides an overview of tyrosine kinase inhibitors targeting VEGF and KIT, BRAF and MEK inhibitors, TLR9 agonist, STAT3 inhibitors, and immune checkpoint blockers (PD1/PDL-1 inhibitors), for which recent advances have been reported. These new agents have the potential to provide benefits to CRC patients with unmet medical needs

Chemo- and enantio-selective reversed-phase HPLC analysis of rosuvastatin using a cellulose-based chiral stationary phase in gradient elution mode

A direct reversed-phase high-performance liquid chromatographic (HPLC) method was developed for deter-mining the content of the enantiomeric impurity of the chiral statin rosuvastatin calcium salt (RSV) in com-mercial tablets. The baseline enantioseparation was achieved using the Lux Cellulose-2 column and a binary linear gradient of acetonitrile and trifluoroacetic acid 0.05% in an aqueous solution. The flow rate of the mobile phases and column temperature were set at 1.0 mL min- 1 and 40 degrees C, respectively. In comparison with the isocratic HPLC method reported in the European Pharmacopoeia (EP) monograph for RSV, the gradient elution method offered improved chemo-and enantio-selectivity and reduced analysis times. The limits of quantitation and detection of the enantiomeric impurity were found to be 0.15 and 0.05 mu g mL-1