Ruthenium(II) complexes containing PEGylated N-heterocyclic carbene ligands for tunning biocompatibility in the fight against cancer.

A synthetic procedure was designed for the preparation and characterization of Ag and Ru complexes containing NHC ligands functionalized with PEG fragments. Stability studies were conducted to gain insight of the species in water and other solvents like DMSO, or with reagents like imidazole as representative group for histidine amino acid. The presence of Cl atoms instead of H in the 4,5 positions of the N-heterocyclic carbene afforded higher water stability.

Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring.

Due to the rise in overnutrition, the incidence of obesity-induced hepatocellular carcinoma (HCC) will continue to escalate; however, our understanding of the obesity to HCC developmental axis is limited. We constructed a single-cell atlas to interrogate the dynamic transcriptomic changes during hepatocarcinogenesis in mice. Here we identify fatty acid binding protein 5 (FABP5) as a driver of obesity-induced HCC.

Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage.

Midlobular hepatocytes are proposed to be the most plastic hepatic cell, providing a reservoir for hepatocyte proliferation during homeostasis and regeneration. However, other mechanisms beyond hyperplasia have been little explored and the contribution of other hepatocyte subpopulations to regeneration has been controversial. Thus, re-examining hepatocyte dynamics during regeneration is critical for cell therapy and treatment of liver diseases.

Diabetic individuals with COVID-19 exhibit reduced efficacy of gliptins in inhibiting dipeptidyl peptidase 4 (DPP4). A suggested explanation for increased COVID-19 susceptibility in patients with type 2 diabetes mellitus (T2DM).

Aims: Dipeptidyl peptidase 4 (DPP4) has been proposed as a coreceptor for SARS-CoV-2 cellular entry. Considering that type 2 diabetes mellitus (T2DM) has been identified as the most important risk factor for SARS-CoV-2, and that gliptins (DPP4 inhibitors) are a prescribed diabetic treatment, this study aims to unravel the impact of DPP4 in the intersection of T2DM/COVID-19.

Materials And Methods: We analyzed 189 serum human samples, divided into six clinical groups (controls, T2DM, T2DM + gliptins, COVID-19, COVID-19 + T2DM, and COVID-19 + T2DM + gliptins), measuring DPP4 protein concentration and activity by Western blot, ELISA, and commercial activity kits.

Resistance to 2-Hydroxy-Flutamide in Prostate Cancer Cells Is Associated with the Downregulation of Phosphatidylcholine Biosynthesis and Epigenetic Modifications.

In this study, we examined the metabolic adaptations of a chemoresistant prostate cancer cell line in comparison to a sensitive cell line. We utilized prostate cancer LNCaP cells and subjected them to a stepwise increase in the antiandrogen 2-hydroxy-flutamide (FLU) concentration to generate a FLU-resistant cell line (LN-FLU). These LN-FLU cells displayed characteristics of cancer stem cells, exhibited drug resistance, and showed a significantly reduced expression of Cyclin D1, along with the overexpression of p16, pointing to a proliferation arrest.

Alteration of the HIF-1α/VEGF Signaling Pathway and Disruption of the Cell Cycle by Second Generation Carbosilan Dendrimers.

Current therapies against prostate cancer (PCa) disease, such as surgery, radiotherapy, or in last term chemical castration by androgen deprivation, have led to significant reduction of the incidence of PCa throughout the world. Worse prognosis is found in those patients which exhibit castration resistance, relapsing into the disease with even greater aggressiveness. Hypoxia cancer cell adaption has been observed to be closely connected to fatal prognostic tumor features.

A Highly Sensitive Immunoassay for Determination of Immune Response to SARS-CoV-2 in Capillary Blood Samples.

Throughout the pandemic, serological assays have been revealed as crucial for detecting previous exposures to the virus and determining the timing of antibody maintenance after vaccination or natural infection. This study aimed to develop an optimized enzyme-linked immunosorbent assay (ELISA)-based serology, which could be used in case of reagent shortages, such as that occurred in the beginning of this health emergency. As a result, we present a high-sensitive immunoassay for the determination of IgG levels in venous serum samples, using 2 μg/mL antigen (receptor-binding domain of the spike protein S1) for coating the plate and utilizing human samples at a dilution 1:1000.

Metabolic fingerprinting of chemotherapy-resistant prostate cancer stem cells. An untargeted metabolomic approach by liquid chromatography-mass spectrometry.

Chemoresistance is one of the most important challenges in cancer therapy. The presence of cancer stem cells within the tumor may contribute to chemotherapy resistance since these cells express high levels of extrusion pumps and xenobiotic metabolizing enzymes that inactivate the therapeutic drug. Despite the recent advances in cancer cell metabolism adaptations, little is known about the metabolic adaptations of the cancer stem cells resistant to chemotherapy.

Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology.

DPP4/CD26 is a single-pass transmembrane protein with multiple functions on glycemic control, cell migration and proliferation, and the immune system, among others. It has recently acquired an especial relevance due to the possibility to act as a receptor or co-receptor for SARS-CoV-2, as it has been already demonstrated for other coronaviruses. In this review, we analyze the evidence for the role of DPP4 on COVID-19 risk and clinical outcome, and its contribution to COVID-19 physiopathology.

The Natural Chemotherapeutic Capsaicin Activates AMPK through LKB1 Kinase and TRPV1 Receptors in Prostate Cancer Cells.

The natural bioactive compound capsaicin has been reported to have anticancer activity, although the underlying mechanism of action has not been completely clarified. Herein, we investigated the mechanism whereby capsaicin exerts antitumor effects on prostate cancer cells. We found that capsaicin activated AMP-activated kinase (AMPK) and promoted cell death in the LKB1-expressing prostate cancer cell lines LNCaP and PC3, but not in the liver kinase B1 (LKB1)-null cell line DU-145.

Increase in Ischemia-Modified Albumin and Pregnancy-Associated Plasma Protein-A in COVID-19 Patients.

This study was undertaken due to the urgent need to explore reliable biomarkers for early SARS-CoV-2 infection. We performed a retrospective study analyzing the serum levels of the cardiovascular biomarkers IL-6, TNF-α, N-terminal pro-B natriuretic peptide, cardiac troponin T (cTnT), ischemia-modified albumin (IMA) and pregnancy-associated plasma protein-A (PAPP-A) in 84 patients with COVID-19.Patients were divided into three groups according to their RT-qPCR and IgG values: acute infection ( = 35), early infection ( = 25) or control subjects ( = 24).

Androgen Deprivation Induces Reprogramming of Prostate Cancer Cells to Stem-Like Cells.

In the past few years, cell plasticity has emerged as a mode of targeted therapy evasion in prostate adenocarcinoma. When exposed to anticancer therapies, tumor cells may switch into a different histological subtype, such as the neuroendocrine phenotype which is associated with treatment failure and a poor prognosis. In this study, we demonstrated that long-term androgen signal depletion of prostate LNCaP cells induced a neuroendocrine phenotype followed by re-differentiation towards a "stem-like" state.

Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells.

According to the stem cell theory for cancer, hepatocellular carcinomas are sustained by a group of cancer stem cells (CSCs) which are responsible for resistance to chemotherapy. In the present study we aimed to examine lipid metabolism in cancer stem cells induced by long-term treatment with sorafenib and its relationship with acquisition of a CSC-like phenotype. Two cell lines (HepG2SF1 and Huh7SF1) were generated by incubation with a step-wise increase of sorafenib concentrations for 10 months.

Capsaicin Targets Lipogenesis in HepG2 Cells Through AMPK Activation, AKT Inhibition and PPARs Regulation.

Obesity, a major risk factor for chronic diseases such as type 2 diabetes (T2D), represents a serious primary health problem worldwide. Dietary habits are of special interest to prevent and counteract the obesity and its associated metabolic disorders, including lipid steatosis. Capsaicin, a pungent compound of chili peppers, has been found to ameliorate diet-induced obesity in rodents and humans.

Targeting AMP-activated kinase impacts hepatocellular cancer stem cells induced by long-term treatment with sorafenib.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. HCC treatment is hindered by the frequent emergence of chemoresistance to the multikinase inhibitor sorafenib, which has been related to the presence of cancer stem cells (CSCs) that self-renew and often escape therapy. The key metabolic sensor AMP-activated kinase (AMPK) has recently been recognized as a tumour growth regulator.

Combination of the natural product capsaicin and docetaxel synergistically kills human prostate cancer cells through the metabolic regulator AMP-activated kinase.

Background: Current chemotherapy for castration-resistant prostate cancer is established on taxane-based compounds like docetaxel. However, eventually, the development of toxic side effects and resistance limits the therapeutic benefit being the major concern in the treatment of prostate cancer. Combination therapies in many cases, enhance drug efficacy and delay the appearance of undesired effects, representing an important option for the treatment of castration-resistant prostate cancer.

The red pepper's spicy ingredient capsaicin activates AMPK in HepG2 cells through CaMKKβ.

Capsaicin is a natural compound present in chili and red peppers and the responsible of their spicy flavor. It has recently provoked interest because of its antitumoral effects in many cell types although its action mechanism is not clearly understood. As metabolic dysregulation is one of the hallmarks of cancer cells and the key metabolic sensor in the AMP-activated kinase (AMPK), in this study we explored the ability of capsaicin to modulate AMPK activity.

Hierarchical Self-Assembly of BODIPY Dyes as a Tool to Improve the Antitumor Activity of Capsaicin in Prostate Cancer.

Capsaicin (CAP) has been long known for its analgesic properties and more recently for its antitumor activity in various cell types. However, its pungency and the high doses needed to achieve a significant activity have precluded its application in cancer therapy. Herein, we propose a straightforward novel strategy to improve the antitumor effect of CAP based on the enhancement of its aggregation propensity in aqueous media by covalent attachment of a BODIPY (BDP) dye.

Identification of a novel 2-oxindole fluorinated derivative as in vivo antitumor agent for prostate cancer acting via AMPK activation.

The key metabolic sensor adenosine monophosphate-dependent kinase (AMPK) has emerged as a promising therapeutic target for cancer prevention and treatment. Besides its role in energy homeostasis, AMPK blocks cell cycle, regulates autophagy and suppresses the anabolic processes required for rapid cell growth. AMPK is especially relevant in prostate cancer in which activation of lipogenic pathways correlate with tumor progression and aggressiveness.

Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation.

In this study, we investigated the antitumoral effects of combined treatment using sorafenib and capsaicin in hepatocellular carcinoma (HCC) cells. Here we showed that the combination of the two drugs had a much stronger inhibitory effect on both HepG2 and Huh-7 human HCC cells growth than either drug alone. The isobolograms demonstrated that the combinations investigated in this study produced a synergistic interaction.

Effects of JWH015 in cytokine secretion in primary human keratinocytes and fibroblasts and its suitability for topical/transdermal delivery.

Background JWH015 is a cannabinoid (CB) receptor type 2 agonist that produces immunomodulatory effects. Since skin cells play a key role in inflammatory conditions and tissue repair, we investigated the ability of JWH015 to promote an anti-inflammatory and pro-wound healing phenotype in human primary skin cells. Methods Human primary keratinocytes and fibroblasts were stimulated with lipopolysaccharide.

Up-Regulated Expression of LAMP2 and Autophagy Activity during Neuroendocrine Differentiation of Prostate Cancer LNCaP Cells.

Neuroendocrine (NE) prostate cancer (PCa) is a highly aggressive subtype of prostate cancer associated with resistance to androgen ablation therapy. In this study, we used LNCaP prostate cancer cells cultured in a serum-free medium for 6 days as a NE model of prostate cancer. Serum deprivation increased the expression of NE markers such as neuron-specific enolase (NSE) and βIII tubulin (βIII tub) and decreased the expression of the androgen receptor protein in LNCaP cells.

The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells.

Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable.