29 research outputs found
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
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
4-(3-Phenylsulfonylindol-2-yl)-1-(pyridin-2-yl)piperazinyl-methanones as Potent Inhibitors of both SARS-CoV-2 and HCoV-OC43 Viruses
Morphological alteration induced by Cytochalasin D on serous cells of human submandibular gland in basal and stimulated conditions
Cytochalasin D (CD) is a fungal toxin which binds to the faster growing end of actin microfilament and inhibits actin polymerization. By an in vitro incubation system of slices of human submandibular glands obtained at surgery, we investigated by light microscope (LM), transmission electron microscope (TEM), and high resolution scanning electron microscope (HRSEM) the morphological changes caused by CD on serous cells. We studied the effects of the drug on secretory events induced by isoproterenol (I) and carbachol (C). With LM, following CD incubation, canaliculi were enlarged and prominent vacuoles were seen throughout the cytoplasm. By TEM, the vacuoles, which in many cases were in continuity with the lumen, represented the distinctive feature of secretory cells. With HRSEM, intercellular canaliculi, seen from their cytoplasmic side, exhibited many small spherical bulges, corresponding to the coated pits seen with TEM and indicating that the retrieval of plasma membrane was arrested at an early phase by the disruption of the actin cytoskeleton. In specimens treated with secretagogues and CD, a consequence reported here for the first time was the presence of dense granules within the vacuoles. The protrusions seen by HRSEM on the cytoplasmic side of intercellular canaliculi, following secretagogues stimulations, appeared peculiar to each stimulants, even if combined with CD, suggesting that besides actin filaments, other components, unaffected by CD, also are involved in the process of exocytosis and related phenomena
Serous and mucous cells of human submandibular salivary gland stimulated in vitro by isoproterenol, carbachol and clozapine. An LM, TEM and HRSEM study
We have investigated by LM, TEM, and HRSEM the effects of D,L-isoproterenol (beta-adrenergic agent), carbachol (muscarinic agent) and clozapine on biopsy specimens of human submandibular gland stimulated in vitro in an inorganic oxygenated medium. Clozapine is a dibenzodiazepine derivative used in psychotic patients that provokes hypersalivation, a displeasing side effect that often causes discontinuance of therapy. Our findings demonstrate that clozapine acts on salivary mucous and seromucous (serous) cells of the gland as a muscarinic agonist. However, the induced secretory response seems to differ qualitatively and quantitatively from that resulting from carbachol. Thus, in agreement with published data resulting from therapeutic treatments and from experimental studies on rats, the mechanism of clozapine induced hypersialorrhea remains open to further investigation