Evaluation of cytotoxic properties of two fluorescent fac-Re(CO)3 complexes bearing an N,N-bidentate benzimidazole coligand.

The reaction between 1H-benzimidazol-2-ylmethyl-(N-aryl)amine derivatives (LR) and [ReBr(CO)5] afforded octahedral Re(i) complexes of the general formula of [ReBr(CO)3LR] (R = 4-Cl and 4-COOCH3). The Re(i) complexes were screened for their potential cytotoxicity against three malignant cell lines and one normal cell line of different origins. The solvatochromic characteristics of the complexes were examined by UV/vis. spectroscopy with the aid of time-dependent density functional theory calculations. Strong autofluorescence emission can be seen in the two Re(i) complexes between 460 and 488 nm. They appeared to accumulate inside intercellular connections and surrounding cellular membranes. The substances gathered also, along the cell membrane, waiting for their entry. The mode of cell death staining and the DNA fragmentation analysis revealed that the 4-Cl complex showed increased apoptotic changes in the MCF-7, and the Caco-2 cell line, while the HepG2 cell line showed little apoptotic changes.

Light-activated cytotoxicity of dicarbonyl Ru(II) complexes with a benzimidazole coligand towards breast cancer.

Reaction between [RuCl2(CO)2]n and 1H-benzimidazol-2-ylmethyl-(N-phenyl)amine ligands (LR) functionalized with various electron-donating and electron-withdrawing substituents on the phenyl ring (R = H, 4-CH3, 4-Cl, 4-COOCH3, and 3-COOCH3) afforded the dark-stable photoactivatable carbon monoxide prodrugs of the general formula [RuCl2(CO)2LR]. Release of the CO molecules from the Ru(II) compounds was examined by monitoring the electronic and IR spectra upon illumination at 365 nm. A noticeable decrease in the intensities of the two characteristic ν(CO) modes for Ru(CO)II2 species, and the growth of two new bands for the mono-carbonyl species and free CO, were the main features of the photolysis profiles. The cytotoxicity of the complexes towards breast cancer (MCF-7) cells was assessed with and without illumination at 365 nm. All the complexes except that with a 4-COOCH3 group (IC50 = 45.08 ± 3.5 µM) are nontoxic under dark conditions. Upon illumination, all the compounds acquired cytotoxicity in the following order: H > 4-COOCH3 > 4-CH3 > 4-Cl > 3-COOCH3. Investigation of the cytotoxicity of the CO-depleted fragments showed that the light-induced cytotoxicity can be attributed to the liberated CO and CO-depleted metal fragments, including the liberated benzimidazole ligands.

Salivary markers and coronavirus disease 2019: insights from cross-talk between the oral microbiome and pulmonary and systemic low-grade inflammation and implications for vascular complications.

To date, coronavirus disease 2019 (COVID-19) has affected over 6.2 million individuals worldwide, including 1.46 million deaths. COVID-19 complications are mainly induced by low-grade inflammation-causing vascular degeneration. There is an increasing body of evidence that suggests that oral dysbiotic taxa are associated with worse prognosis in COVID-19 patients, especially the Prevotella genus, which was retrieved from nasopharyngeal and bronchoalveolar lavage samples in affected patients. Oral dysbiosis may act by increasing the likelihood of vascular complications through low-grade inflammation, as well as impairing respiratory mucosal barrier mechanisms against SARS-CoV-2. Salivary markers can be used to reflect this oral dysbiosis and its subsequent damaging effects on and the lungs and vasculature. Salivary sampling can be self-collected, and is less costly and less invasive, and thus may be a superior option to serum markers in risk stratification of COVID-19 patients. Prospective studies are needed to confirm such hypothesis. Video Abstract: http://links.lww.com/CAEN/A28.

Hypoxia-inducible factor (HIF): The link between obesity and COVID-19.

The COVID-19 death toll has involved to date more than 1 million confirmed deaths. The death rate is even higher in the obese COVID-19 patients, as a result of hypoxia, due to the interplay between adipose tissue hypoxia and obstructive sleep apnea. The discrepancy of manifestations seen in COVID-19 seems to be mediated by a differential immune response rather than a differential viral load. One of the key players of the immune response is HIF. HIF-1ß is a stable constitutively expressed protein in the nucleus; and under hypoxic changes, its activity is unaffected, whereas the HIF-α subunit has a short half-life and because of its degradation by an enzyme known as propyl hydroxylase; under hypoxic conditions, propyl hydroxylase gets deactivated thus leading to the stabilization of HIF-1α. As mentioned before, HIF-1α expression is triggered by hypoxic states, this crippling condition will aggravate the pro-inflammatory characteristics of HIF-1α. The vast majority of decompensated COVID19 cases manifest with drastic lung injury and severe viral pneumonia, the infection-induced hypoxia will the existing hypoxia in obesity. This will additionally augment HIF-1α levels that will provoke the already existing cytokines' storm to fulminant. Consequently, this will directly correlate the effect of a hypoxic environment with the increase of HIF-1α level. HIFɑ exists in two main isoforms HIF-1α and HIF-2α. HIF-1α and HIF-2α act in distinct ways in how they work on different target genes. For example, HIF-2α may act on hemopoietin genes (heme-regulating genes); while HIF-1α acts on EPO. HIF-1α release seems to be markedly augmented in obesity due to adipose tissue hypoxia and obstructive sleep apnea resulting in cyclic hypoxia. HIF-1α can also be secreted by direct viral proteolytic effects. Whereas, HIF-2α is stimulated by chronic hypoxia. HIF-1α exerts detrimental effects on the immune system, characterized by unopposed pro-inflammation at the macrophages, dendritic cells, T cells, and complement levels resulting in cytokines' storm, which is linked to the poor outcomes of COVID-19. On the other hand, HIF-2α role is regulatory and largely opposes the actions mediated by HIF-1α. In view of this, inhibiting HIF-1α release or switching its production to HIF-2α by natural products such as resveratrol or by synthetic drugs, offer a good therapeutic strategy that can prevent COVID-19 worst outcome in infected patients. The approach of breaking the vicious circle between lung damage-induced hypoxia and HIF-1α pro-inflammatory stimulant through drugs is considered to be extremely promising as a therapeutic manner to combat further deterioration of COVID19 cases.

The Dental Pulp Stem/Progenitor Cells-Mediated Inflammatory-Regenerative Axis.

Relying on their ease of isolation and remarkable tissue reparative/regenerative potential, dental pulp stem/progenitor cells (DPSCs) gained pronounced importance in the field of regenerative dentistry. Though inflammation is classically considered the reason for the damage of the dentin-pulpal complex, it continues to be an essential stage of any dentin-pulpal tissue repair or regeneration procedures. During their performance of a pulpal tissue repair or regeneration actions, DPSCs interact with their inflammatory microenvironment locally, possibly influencing their fate and the result of any DPSCs-mediated dentin-pulpal reparative/regenerative endeavor. Hence, this review aims at comprehensively elaborating on these complex interactions of DPSCs with their local pulpal inflammatory microenvironment, particularizing on the inflammatory aspects, affecting DPSCs' stemness, homing/migration, proliferation, differentiation as well as immunomodulation characteristics, and the potentially fundamental intracellular processes involved and their anticipated association with the noncanonical as well as canonical Wnt/ß-Catenin intracellular signaling. Impact Statement This review particularizes on the current state of knowledge on the complex interrelation between dental pulp stem/progenitor cells and their pulpal inflammatory microenvironment; elaborates on inflammation aspects affecting their stemness, proliferation, migration/homing, differentiation and immunomodulation characteristics, and the fundamental intracellular processes involved and their anticipated association with the canonical and noncanonical Wnt pathways. All these aspects could significantly affect the dento-pulpal regenerative therapeutic approaches in vivo.

Effect of the taxonomic group of fungi and type of substrate on the antioxidant activity of a solid-state fermentation system

The enzymatic and non-enzymatic antioxidant activities of a solid-state fermentation system (SSFS) employing six basidiomycete and four ascomycete fungi on orange peel have been evaluated. Class comparisons revealed highly significant effect of fungal group on the antioxidant activity. Peroxidase activity appeared only in the basidiomycete fungi (particularly Pleurotus columbinus, Ganoderma resinaceum, and Pleurotus floridanus) whereas catalase activity appeared in the two fungal groups in favor of the ascomycetes (particularly Paecilomyces variotii and Aspergillus fumigatus). Maximal peroxidase and minimal catalase activities were found at moderate phenolic content, with extreme phenolic levels leading to low peroxidase activity but high catalase activity. Production of the non-enzymatic antioxidants (phenolics, flavonoids, reducing power, and DPPH scavenging) was in favor of the ascomycetes, which showed great native ability to synthesize flavonoids and also to release flavonoids from orange peel. The basidiomycete fungi, which have limited native ability to produce phenolics, had high ability to consume orange peel phenolics. By contrast, the ascomycete fungi exhibited great native ability for production of phenolics and low ability to consume exogenous phenolics

No disponible

Effect of the taxonomic group of fungi and type of substrate on the antioxidant activity of a solid-state fermentation system.

The enzymatic and non-enzymatic antioxidant activities of a solid-state fermentation system (SSFS) employing six basidiomycete and four ascomycete fungi on orange peel have been evaluated. Class comparisons revealed highly significant effect of fungal group on the antioxidant activity. Peroxidase activity appeared only in the basidiomycete fungi (particularly Pleurotus columbinus, Ganoderma resinaceum, and Pleurotus floridanus) whereas catalase activity appeared in the two fungal groups in favor of the ascomycetes (particularly Paecilomyces variotii and Aspergillus fumigatus). Maximal peroxidase and minimal catalase activities were found at moderate phenolic content, with extreme phenolic levels leading to low peroxidase activity but high catalase activity. Production of the non-enzymatic antioxidants (phenolics, flavonoids, reducing power, and DPPH scavenging) was in favor of the ascomycetes, which showed great native ability to synthesize flavonoids and also to release flavonoids from orange peel. The basidiomycete fungi, which have limited native ability to produce phenolics, had high ability to consume orange peel phenolics. By contrast, the ascomycete fungi exhibited great native ability for production of phenolics and low ability to consume exogenous phenolics.