Origin of Chromosome 12 Trisomy Surge in Human Induced Pluripotent Stem Cells (iPSCs).

Cultured pluripotent stem cells are unique in being the only fully diploid immortal human cell lines. However, during continued culture they can acquire significant chromosome abnormalities. Chromosome 12 trisomy is the most common whole-chromosome abnormality found during culture of human induced pluripotent stem cells (iPSCs).

Cannabidiol and Its Combinations with Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis and Inhibit Activation of NF-κB Signaling in Vulvar Squamous Cell Carcinoma.

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with a relatively good prognosis. However, the prognosis remains poor for elderly patients and those with a significant depth of tumor invasion; thus, novel treatment modalities are needed. The aim of this study was to analyze the impact of cannabidiol (CBD) and its combination with NSAIDs, diclofenac (DIC) and ibuprofen (IBU) on VSCC cells.

Indomethacin and Diclofenac Hybrids with Oleanolic Acid Oximes Modulate Key Signaling Pathways in Pancreatic Cancer Cells.

Our earlier studies showed that coupling nonsteroidal anti-inflammatory drugs (NSAIDs) with oleanolic acid derivatives increased their anti-inflammatory activity in human hepatoma cells. The aim of this study was to evaluate their effect on the signaling pathways involved in inflammation processes in human pancreatic cancer (PC) cells. Cultured PSN-1 cells were exposed for 24 h (30 µM) to OA oxime (OAO) derivatives substituted with benzyl or morpholide groups and their conjugates with indomethacin (IND) or diclofenac (DCL).

Anti-SARS-CoV-2 Strategies and the Potential Role of miRNA in the Assessment of COVID-19 Morbidity, Recurrence, and Therapy.

Recently, we have experienced a serious pandemic. Despite significant technological advances in molecular technologies, it is very challenging to slow down the infection spread. It appeared that due to globalization, SARS-CoV-2 spread easily and adapted to new environments or geographical or weather zones.

Anti-Cancer Potential of Synthetic Oleanolic Acid Derivatives and Their Conjugates with NSAIDs.

Naturally occurring pentacyclic triterpenoid oleanolic acid (OA) serves as a good scaffold for additional modifications to achieve synthetic derivatives. Therefore, a large number of triterpenoids have been synthetically modified in order to increase their bioactivity and their protective or therapeutic effects. Moreover, attempts were performed to conjugate synthetic triterpenoids with non-steroidal anti-inflammatory drugs (NSAIDs) or other functional groups.

Conjugation of Diclofenac with Novel Oleanolic Acid Derivatives Modulate Nrf2 and NF-κB Activity in Hepatic Cancer Cells and Normal Hepatocytes Leading to Enhancement of Its Therapeutic and Chemopreventive Potential.

Combining NSAIDs with conventional therapeutics was recently explored as a new strategy in cancer therapy. Our earlier studies showed that novel oleanolic acid oximes (OAO) conjugated with aspirin or indomethacin may enhance their anti-cancer potential through modulation of the Nrf2 and NF-κB signaling pathways. This study focused on the synthesis and biological evaluation of four diclofenac (DCL)-OAO derivative conjugates in the context of these pathways' modification and hepatic cells survival.

The Effect of Novel Oleanolic Acid Oximes Conjugated with Indomethacin on the Nrf2-ARE And NF-κB Signaling Pathways in Normal Hepatocytes and Human Hepatocellular Cancer Cells.

Nrf2 and NF-κB play a key role in inflammation-driven cancers. Conjugation of anti-inflammatory drugs with oleanolic acid oxime (OAO) may enhance their therapeutic potential as a result of downregulation of these pathways. Novel OAO derivatives conjugated with indomethacin (IND) were synthesized, and their effect on the activation and expression of Nrf2 and NF-κB in HepG2 hepatoma cells and THLE-2 immortalized normal hepatocytes was evaluated in relation to cell cycle arrest and apoptosis.

Activation of the Nrf2 response by oleanolic acid oxime morpholide (3-hydroxyiminoolean-12-en-28-oic acid morpholide) is associated with its ability to induce apoptosis and inhibit proliferation in HepG2 hepatoma cells.

Our previous study demonstrated that new oleanolic acid oxime (OAO) derivatives and their conjugates with aspirin (ASP) inhibit NF-κB activation. Evidence exists that the downregulation of NF-κB negatively interferes with the Nrf2 signaling pathway. This study aimed to evaluate the effect of these compounds on Nrf2 activation and its cellular consequences in human hepatoma HepG2 cells and immortalized normal hepatocytes THLE-2.

Oleanolic acid oxime derivatives and their conjugates with aspirin modulate the NF-κB-mediated transcription in HepG2 hepatoma cells.

The aim of this study was to evaluate the effect of new oleanolic acid oxime (OAO) derivatives and their conjugates with aspirin (ASP) on the expression and activation of NF-κB in human hepatoma HepG2 cells. OAO derivatives showed a stronger cytotoxic effect against HepG2 cells compared with their conjugates with aspirin. Moreover, conjugation of OAO with ASP led to enhanced downregulation of NF-κB expression and activation.

Morpholide derivative of the novel oleanolic oxime and succinic acid conjugate diminish the expression and activity of NF-κB and STATs in human hepatocellular carcinoma cells.

Naturally occurring oleanolic acid (OA) possesses a hepatoprotective activity and ability to inhibit proliferation of human hepatocellular carcinoma cells. Both properties might be related to its anti-inflammatory activity. Its low bioavailability justifies the search for more hydrophilic OA derivatives.