Evolving genetic code

In 1985, we reported that a bacterium, Mycoplasma capricolum, used a deviant genetic code, namely UGA, a “universal” stop codon, was read as tryptophan. This finding, together with the deviant nuclear genetic codes in not a few organisms and a number of mitochondria, shows that the genetic code is not universal, and is in a state of evolution. To account for the changes in codon meanings, we proposed the codon capture theory stating that all the code changes are non-disruptive without accompanied changes of amino acid sequences of proteins. Supporting evidence for the theory is presented in this review. A possible evolutionary process from the ancient to the present-day genetic code is also discussed

Endoscopic Ultrasound-Guided Pancreatic Transmural Stenting and Transmural Intervention

Endoscopic ultrasound (EUS)-guided pancreatic access is an emergent method that can be divided into the two main techniques of EUS-guided rendezvous and pancreatic transmural stenting (PTS). While many reports have described EUS-guided procedures, the indications, technical tips, clinical effects, and safety of EUS-guided pancreatic duct drainage (EUS-PD) remain controversial. This review describes the current status of and problems associated with EUS-PD, particularly PTS. We reviewed clinical data derived from a total of 334 patients. Rates of technical and clinical success ranged from 63% to 100% and 76% to 100%, respectively. In contrast, the rate of procedure-related adverse events was high at 26.7% (89/334). The most frequent adverse events comprised abdominal pain (n=38), acute pancreatitis (n=15), bleeding (n=9), and issues associated with pancreatic juice leakage such as perigastric fluid, pancreatic fluid collection, or pancreatic juice leaks (n=8). In conclusion, indications for EUS-PTS are limited, as is the evidence of its viability, due to the scarcity of expert operators. Despite improvements made to various devices, EUS-PTS remains technically challenging. Therefore, a long-term, large-scale, multicenter study is required to establish this technique as a viable alternative drainage method

Evaluation of the Growth-Inhibitory Spectrum of Three Types of Cyanoacrylate Nanoparticles on Gram-Positive and Gram-Negative Bacteria

The development of novel effective antibacterial agents is crucial due to increasing antibiotic resistance in various bacteria. Poly (alkyl cyanoacrylate) nanoparticles (PACA-NPs) are promising novel antibacterial agents as they have shown antibacterial activity against several Gram-positive and Gram-negative bacteria. However, the antibacterial mechanism remains unclear. Here, we compared the antibacterial efficacy of ethyl cyanoacrylate nanoparticles (ECA-NPs), isobutyl cyanoacrylate NPs (iBCA-NPs), and ethoxyethyl cyanoacrylate NPs (EECA-NPs) using five Gram-positive and five Gram-negative bacteria. Among these resin nanoparticles, ECA-NPs showed the highest growth inhibitory effect against all the examined bacterial species, and this effect was higher against Gram-positive bacteria than Gram-negative. While iBCA-NP could inhibit the cell growth only in two Gram-positive bacteria, i.e., Bacillus subtilis and Staphylococcus aureus, it had negligible inhibitory effect against all five Gram-negative bacteria examined. Irrespective of the differences in growth inhibition induced by these three NPs, N-acetyl-L-cysteine (NAC), a well-known reactive oxygen species (ROS) scavenger, efficiently restored growth in all the bacterial strains to that similar to untreated cells. This strongly suggests that the exposure to NPs generates ROS, which mainly induces cell growth inhibition irrespective of the difference in bacterial species and cyanoacrylate NPs used

Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients

Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab.Materials and methods: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line.Results: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6 months) and atezolizumab plus bev-acizumab first-line (15.7 months; p = 0.12; hazard ratio [HR] = 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who under-went trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8 months, p < 0.01; HR = 0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p < 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0 months) and those who under-went TACE (15.9 months) had a significative longer OS than patients treated with sorafenib (14.2 months; respectively, p = 0.01; HR = 0.45, and p < 0.05; HR = 0.46).Conclusion: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy

Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab

Background In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors. Objective This retrospective multicenter real-world study aims to investigate the potential prognostic value of AEs in patients with HCC treated with atezolizumab plus bevacizumab in the first-line setting. Patients and methods The study population consisted of 823 patients from five countries (Italy, Germany, Portugal, Japan, and the Republic of Korea). Results Of the patients, 73.3% presented at least one AE during the study period. The most common AEs were proteinuria (29.6%), arterial hypertension (27.2%), and fatigue (26.0%). In all, 17.3% of the AEs were grade (G) 3. One death due to bleeding was reported. The multivariate analysis confirmed the appearance of decreased appetite G < 2 [versus G >= 2; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.13-0.90; p < 0.01] and immunotoxicity G < 2 (versus G >= 2; HR: 0.70; 95% CI 0.24-0.99; p = 0.04) as independent prognostic factors for overall survival, and the appearance of decreased appetite G < 2 (versus G >= 2; HR: 0.73; 95% CI 0.43-0.95; p = 0.01), diarrhea (yes versus no; HR: 0.57, 95% CI 0.38-0.85; p = 0.01), fatigue (yes versus no; HR: 0.82, 95% CI 0.65-0.95; p < 0.01), arterial hypertension G < 2 (versus G >= 2; HR: 0.68, 95% CI 0.52-0.87; p < 0.01), and proteinuria (yes versus no; HR: 0.79, 95% CI 0.64-0.98; p = 0.03) as independent prognostic factors for progression-free survival. Conclusions As demonstrated for other therapies, there is also a correlation between the occurrence of AEs and outcomes for patients with HCC for the combination of atezolizumab plus bevacizumab