The effects of autophagy-modifying drugs chloroquine and lithium on the skin melanoma microenvironment.

Background: Skin melanoma is a highly metastatic cancer with an increasing global incidence. Despite advancements in immunotherapy, new treatment strategies based on tumor biology are essential for improving outcomes and developing novel therapies. Autophagy plays a critical role in melanoma cell metabolism and affects the tumor microenvironment (TME).

Ultrastructural organization of the liver of rat pups in early postnatal ontogenesis when pregnant and lactating rats are kept on a low-protein diet.

Protein deficiency in the diet during pregnancy and lactation has a serious impact on the offspring by programming a predisposition to such serious diseases as hypertension and type 2 diabetes mellitus. In our study, we examined liver ultrastructure of rat pups at ages 2, 21, and 40 days with maternal protein deficiency. Body weight of the pups progressively lagged behind the control throughout the experiment, and the timing of eye opening indicated a slowdown of development.

Reversed Corneal Fibroblasts Therapy Restores Transparency of Mouse Cornea after Injury.

Cell-based therapies using corneal stromal stem cells (CSSC), corneal keratocytes, or a combination of both suppress corneal scarring. The number of quiescent keratocytes in the cornea is small; it is difficult to expand them in vitro in quantities suitable for transplantation. This study examined the therapeutic effect of corneal fibroblasts reversed into keratocytes (rCF) in a mouse model of mechanical corneal injury.

The Expression of Markers of Acute Kidney Injury Kim1 and NGAL after Administration of High Doses of Lithium Carbonate in Mice with Engrafted Skin Melanoma B16.

The expression of marker proteins of acute kidney injury after administration of high doses of lithium carbonate was assessed to evaluate the possibility of lithium use in neutron capture therapy. In mice with implanted skin melanoma B16, the expression of Kim1 (kidney injury molecule 1) and NGAL (neutrophil gelatinase-associated lipocalin) proteins in the kidneys was evaluated immunohistochemically 15, 30, 90, 180 min, and 7 days after peroral administration of lithium carbonate at single doses of 300 and 400 mg/kg. An increase in the expression of the studied proteins was found in 30 and 90 min after administration of 400 mg/kg lithium carbonate, however, 7 days after the drug administration, the expression returned to the level observed in the control group.

Assessment of Autophagy in Tumor Cells of Human Skin Melanoma of Different Stages.

High levels of autophagy can increase the viability of tumor cells as well as their resistance to chemotherapy. Evaluation of the dynamics of autophagy processes at different stages of carcinogenesis can extend our understanding of melanoma pathogenesis to develop new therapeutic approaches. We performed a comparative study of tumor cell autophagy in stages II and III human skin melanoma.

Lithium salts cytotoxicity and accumulation in melanoma cells in vitro.

Boron neutron capture therapy is a perspective selective technology for the destruction of cancer cells, while the use of lithium instead of boron may represent a new and promising vector for the development of neutron capture therapy (NCT). The aim of the study was a comparative assessment of the cytotoxicity of various lithium salts, as well as an analysis of the accumulation of lithium in tumor cells in vitro to determine the possibility of using lithium in NCT. The cytotoxicity of lithium salts was determined using MTT-test and colony forming assay on human fibroblasts BJ-5ta, human skin melanoma SK-Mel-28, and mouse skin melanoma B16 cell lines.

Intracellular organelles remodeling in myocardial endotheliocytes in COVID-19: an autopsy-based study.

It is known that the unfavorable outcome in patients infected with SARS-CoV-2 may be associated with the development of complications caused by heart damage due to the direct virus action. The mechanism of these cardiovascular injuries caused by SARS-CoV-2 infection has not been fully understood; however, the study of COVID-19-associated myocardial microcirculatory dysfunction can represent the useful strategy to solving this challenge. Thus, here we aimed to study the ultrastructural organization of endothelial cells of myocardial capillaries in patients with COVID-19.

Ultrastructural Reorganization of Endotheliocytes of Pulmonary Blood Capillaries in COVID-19.

The ultrastructural organization endotheliocytes of pulmonary blood capillaries in COVID-19 was studied on autopsy material using electron microscopy. Swelling of the cytoplasm and mitochondria with destruction of the cristae, dilation of the Golgi complex cisternae, a decrease in the volume density of the luminal and basal caveolae and free transport vesicles, an increase of the rough endoplasmic reticulum, as well as the presence of elements of coronavirus replication (reticulovesicular structures, zippered endoplasmic reticulum, electron-dense particles in the Golgi cisternae, and vacuoles with viral particles) were revealed. Further studies of the intracellular mechanisms used by the virus to replicate could help to develop antiviral drugs for the treatment of the new coronavirus infection.

Accumulation and neuroprotective effects of lithium on hepatocellular carcinoma mice model.

Aim: The peripheral tumor growth is accompanied by the accumulation of inflammatory mediators in the blood that can negatively influence blood-brain barrier function and neuronal structure and develop the cancer-associated depression. The aim of the study was to evaluate the neurobiological effects of lithium on hepatocellular carcinoma mice model.

Methods: In this study we analyzed the locomotor activity of lithium-treated tumor-bearing mice using the Phenomaster instrument.

Autophagy and vesicular trafficking in human uveal melanoma: A histopathological study.

Uveal melanoma is an ocular tumor with a high risk of developing metastases. The endo-lysosomal system can affect the melanoma progression by accelerating and facilitating invasion or metastasis. This study aims to conduct comparative analysis of normal choroidal melanocytes and uveal melanoma cells ultrastructure with a focus on intracellular transport system, and to examine the patterns of autophagy- and vesicular trafficking-related proteins expression in a case series of uveal melanomas.

Derivation of Human Corneal Keratocytes from ReLEx SMILE Lenticules for Cell Therapy and Tissue Engineering.

Fibroblasts isolated and expanded from ReLEx SMILE lenticules can be a source of human keratocytes. Since corneal keratocytes are quiescent cells, it is difficult to expand them in vitro in suitable numbers for clinical and experimental use. In the present study, this problem was solved by isolating and growing corneal fibroblasts (CFs) with a high proliferative potential and their reversion to keratocytes in a selective serum-free medium.

Autophagy in Human Retinal Neurons in Glaucoma.

Immunohistochemical and ultrastructural analysis revealed signs of structural alterations in neurons and autophagy in all layers of the human retina at the end-stage glaucoma. The most pronounced destructive changes associated with swelling and destruction of mitochondria, endoplasmic reticulum, and Golgi apparatus, as well as structural signs of impaired synaptic activity and apoptosis were noted in ganglion, bipolar, and amacrine neurons. In the structure of photoreceptor cells, alone with destructive processes associated with structural alterations of rods and cones in the outer membrane discs, as well as swelling of organelles, we observed processes aimed at the maintenance of cell homeostasis.

Lithium Enhances Autophagy and Cell Death in Skin Melanoma: An Ultrastructural and Immunohistochemical Study.

Lithium is an inhibitor of glycogen synthase kinase 3 beta, which is traditionally used in the treatment of bipolar disorders and has antitumor effects. The aim of the current study was to determine if lithium salt causes autophagy and apoptosis in skin melanoma cells to enhance cell death. Light microscopy, transmission electron microscopy, immunohistochemistry, and immunofluorescence were used to study the mechanism of action of lithium carbonate in B16 melanoma cells in vivo.

Trehalose Activates Hepatic and Myocardial Autophagy and Has Anti-Inflammatory Effects in / Diabetic Mice.

mice (carrying a mutation in the gene encoding leptin receptor) show autophagy suppression. Our aim was to evaluate the effect of autophagy inducer trehalose on liver and heart autophagy in mice and to study inflammation dysregulation and the suitability of chitinases' expression levels as diabetes markers. Thirty-eight male mice and C57/BL mice (control) were used.

Treatment with Autophagy Inducer Trehalose Alleviates Memory and Behavioral Impairments and Neuroinflammatory Brain Processes in db/db Mice.

Autophagy attenuation has been found in neurodegenerative diseases, aging, diabetes mellitus, and atherosclerosis. In experimental models of neurodegenerative diseases, the correction of autophagy in the brain reverses neuronal and behavioral deficits and hence seems to be a promising therapy for neuropathologies. Our aim was to study the effect of an autophagy inducer, trehalose, on brain autophagy and behavior in a genetic model of diabetes with signs of neuronal damage (db/db mice).

Ultrastructure of Endothelial Cells of Myocardial Capillaries in Burn Septicotoxemia.

We studied ultrastructure and vesicular structures in endothelial cells of myocardial micro-vessels in burn patients. Electron microscopy revealed a significant decrease in volume density of vesicular structures in the endotheliocytes of myocardial capillaries in patients with burn septicotoxemia. The observed structural signs of endothelial dysfunction revealed in this category of patients can be a promising area for further research and for the development of methods of pathogenetic correction of myocardial disorders in the case of burn injury.

Empagliflozin alleviates podocytopathy and enhances glomerular nephrin expression in diabetic mice.

Background: Modern guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors as the preferred antihyperglycemic agents for patients with type 2 diabetes and chronic kidney disease. However, the mechanisms underlying the renal protective effect of SGLT2 inhibitors are not fully understood.

Aim: To estimate the effect of the SGLT2 inhibitor, empagliflozin (EMPA), on the structure of podocytes and nephrin expression in glomeruli in diabetic mice.

In Vitro Effects of Lithium Carbonate on Cell Cycle, Apoptosis, and Autophagy in Hepatocellular Carcinoma-29 Cells.

We studied the effects of lithium carbonate on the cell cycle, apoptosis, and autophagy in hepatocellular carcinoma-29 cells (HCC-29) in vitro. Flow cytofluorometry analysis revealed accumulation of G2/M-phase HCC-29 cells and increase in the number of apoptotic cells in 48 h after administration of 5 mM lithium carbonate. Induction of autophagy in HCC-29 cells was detected by transmission electron microscopy and immunofluorescence staining.