TRIM/RBCC are a large family of proteins that include more than 80 proteins, most of which act as E3 ligases and catalyze the direct transfer of Ubiquitin, SUMO and ISG15 on specific protein substrates. They are involved in oncogenesis processes and in cellular immunity. On this topic, we focus on TRIM8 and its multiple roles in tumor pathologies. TRIM8 inhibits breast cancer proliferation through the regulation of estrogen signaling. TRIM8 downregulation in glioma is involved in cell proliferation, and it is related to patients’ survival. Several studies suggested that TRIM8 regulates the p53 suppressor signaling pathway: it is involved in the NF-kB pathway (Nuclear Factor kappa light- chain-enhancer of activated B cells) and in STAT3 (Signal Transducer and Activator of Transcription 3) of the JAK-STAT pathway. In this review, we summarize how the association between these different pathways reflects a dual role of TRIM8 in cancer as an oncogene or a tumor suppressor gene.

This study evaluates the effects of five different peptides, the Epitalon^® tetrapeptide, the Vilon^® dipeptide, the Thymogen^® dipeptide, the Thymalin^® peptide complex, and the Chonluten^® tripeptide, as regulators of inflammatory and proliferative processes in the human monocytic THP-1, which is a human leukemia monocytic cell line capable of differentiating into macrophages by PMA in vitro. These peptides (Khavinson Peptides^®), characterized by Prof. Khavinson from 1973 onwards, were initially isolated from animal tissues and found to be organ specific. We tested the capacity of the five peptides to influence cell cultures in vitro by incubating THP-1 cells with peptides at certain concentrations known for being effective on recipient cells in culture. We found that all five peptides can modulate key proliferative patterns, increasing tyrosine phosphorylation of mitogen-activated cytoplasmic kinases. In addition, the Chonluten tripeptide, derived from bronchial epithelial cells, inhibited in vitro tumor necrosis factor (TNF) production of monocytes exposed to pro-inflammatory bacterial lipopolysaccharide (LPS). The low TNF release by monocytes is linked to a documented mechanism of TNF tolerance, promoting attenuation of inflammatory action. Therefore, all peptides inhibited the expression of TNF and pro-inflammatory IL-6 cytokine stimulated by LPS on terminally differentiated THP-1 cells. Lastly, by incubating the THP1 cells, treated with the peptides, on a layer of activated endothelial cells (HUVECs activated by LPS), we observed a reduction in cell adhesion, a typical pro-inflammatory mechanism. Overall, the results suggest that the Khavinson Peptides^® cooperate as natural inducers of TNF tolerance in monocyte, and act on macrophages as anti-inflammatory molecules during inflammatory and microbial-mediated activity.

Background: The mouth and the oropharyngeal system are home to numerous bacterial species that constitute the so-called oral microbiome and play an important role for the integrity of the oral cavity, influencing the overall health of the body, as demonstrated by several studies. The aim of this study was to evaluate the bacterial modulation potential of a toothpaste (bioredoxin) containing curcumin and melatonin. Both substances have anti-inflammatory properties, as documented in several scientific reports. Methods: The in vivo study we present was a single-center, double-blind trial and was conducted in parallel groups. We enlisted 20 volunteers who were randomly assigned to four distinct groups using blinded four different toothpaste preparations: a standard toothpaste indicated as placebo, a toothpaste with curcumin, a toothpaste with melatonin, and a toothpaste with melatonin and curcumin. Results: The samples from the gingival tasks were taken at time 0 and after 8 weeks of toothpaste treatment. By evaluating the DNA content of the most significant periodontal bacteria related to the total bacteria count using quantitative PCR assays, including the saprophyte component of the microbiome, we demonstrated that the Curcumin and Melatonin treatment has a statistically relevant effect on decreasing the level of periodontal pathogenic bacteria DNA. The toothpaste with the addition of curcumin and melatonin showed a modulation between t0 and t1 of the Campylobacter rectus (14,568 vs. 3532.8) and Peptostreptococcus micro (1320.8 vs. 319) bacteria. In addition, a modulation of pathogenic bacteria and saprophytic bacteria was shown. The synergistic action of the two additives would therefore appear to lead to promising results. Conclusions: Despite the fact that additional studies may be necessary in evaluating the effect of the Curcumin/melatonin combination in modulating a proposed therapeutic effect on infections of the oropharyngeal apparatus, in this report, we show for the first time that a combination of curcumin and melatonin supplemented using an oral cosmetic vehicle has the capacity to decrease the level of periodontal pathogenic bacteria, possibly ameliorating health and the physiological conditions in the buccal scenario.