The global prevalence of E-cigarettes in youth: A comprehensive systematic review and meta-analysis.

Objectives: Smoking, especially cigarettes, is known as one of the most common social and health problems among people. E-cigarettes are another form of tobacco that has been an ordinary daily occurrence.Study Design: systematic review and meta-analysis. Methods: Systematic searching of databases was performed in Scopus, Web of Science, PubMed, Science Direct, MagIran, IranDoc, SID and Google search engine based on the PRISMA 2020 guideline. This search was conducted by the end of May 2021. Following full-text assessments, the related data were extracted from the papers. Newcastle-Ottawa scale was also used to evaluate the quality of methodology of the articles. Finally, study analysis was performed using Comprehensive Meta-Analysis software (version 2) based on the random effect model. Results: Global prevalence of E-cigarette in younger individuals was 16.8 (95 % CI: 10.6-25.6) and 4.8 (95 % CI: 3-7.6) in the Ever and Current modes of E-cigarette, respectively. We also found that E-cigarettes were used more common in young boys than young girls in both Ever and Current modes. In young boys, the prevalence of E-cigarette were 18.8 (95 % CI: 8.4-36.8) and 4.9 (95 % CI: 3-8) in both modes of Ever and Current, respectively. In young girls, these factors were 9.9 (95 % CI: 5-18.6) and 1.6 (95 % CI: 1-3.1) in both modes of Ever and Current, respectively. Conclusions: The global prevalence of e-cigarettes among young people, especially young boys, is increasing. Based on this, the prevention and management of the damage of this social phenomenon requires comprehensive global study, planning and policy.

Hepatocellular carcinoma (HCC) immunotherapy by anti-PD-1 monoclonal antibodies: A rapidly evolving strategy.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world, with a high relapse rate. Delayed symptom onset observed in 70-80% of patients leads to diagnosis in advanced stages commonly associated with chronic liver disease. Programmed cell death protein 1 (PD-1) blockade therapy has recently emerged as a promising therapeutic option in the clinical management of several advanced malignancies, including HCC, due to the activation of exhausted tumor-infiltrating lymphocytes and improved outcomes of T-cell function. However, many people with HCC do not respond to PD-1 blockade therapy, and the diversity of immune-related adverse events (irAEs) restricts their clinical utility. Therefore, numerous effective combinatory strategies, including combinations with anti-PD-1 antibodies and other therapeutic methods ranging from chemotherapy to targeted therapies, are evolving to improve therapeutic outcomes and evoke synergistic anti-tumor impressions in patients with advanced HCC. Unfortunately, combined therapy may have more side effects than single-agent treatment. Nonetheless, identifying appropriate predictive biomarkers can aid in managing potential immune-related adverse events by distinguishing patients who respond best to PD-1 inhibitors as single agents or in combination strategies. In the present review, we summarize the therapeutic potential of PD-1 blockade therapy for advanced HCC patients. Besides, a glimpse of the pivotal predictive biomarkers influencing a patient's response to anti-PD-1 antibodies will be provided.

Optimization of expression, purification and secretion of functional recombinant human growth hormone in Escherichia coli using modified staphylococcal protein a signal peptide.

BACKGROUND: Human Growth Hormone (hGH) is a glycoprotein released from the pituitary gland. Due to the wide range of effects in humans, any disruption in hGH secretion could have serious consequences. This highlights the clinical importance of hGH production in the treatment of different diseases associated with a deficiency of this hormone. The production of recombinant mature hormone in suitable hosts and secretion of this therapeutic protein into the extracellular space can be considered as one of the best cost-effective approaches not only to obtain the active form of the protein but also endotoxin-free preparation. Since the natural growth hormone signal peptide is of eukaryotic origin and is not detectable by any of the Escherichia coli secretory systems, including Sec and Tat, and is therefore unable to secrete hGH in the prokaryotic systems, designing a new and efficient signal peptide is essential to direct hGh to the extracellular space. RESULTS: In this study, using a combination of the bioinformatics design and molecular genetics, the protein A signal peptide from Staphylococcus aureus was modified, redesigned and then fused to the mature hGH coding region. The recombinant hGH was then expressed in E. coli and successfully secreted to the medium through the Sec pathway. Secretion of the hGH into the medium was verified using SDS-PAGE and western blot analysis. Recombinant hGH was then expressed in E. coli and successfully secreted into cell culture medium via the Sec pathway. The secretion of hGH into the extracellular medium was confirmed by SDS-PAGE and Western blot analysis. Furthermore, the addition of glycine was shown to improve hGH secretion onto the culture medium. Equations for determining the optimal conditions were also determined. Functional hGH analysis using an ELISA-based method confirmed that the ratio of the active form of secreted hGH to the inactive form in the periplasm is higher than this ratio in the cytoplasm. CONCLUSIONS: Since the native signal protein peptide of S. aureus protein A was not able to deliver hGH to the extracellular space, it was modified using bioinformatics tools and fused to the n-terminal region of hGh to show that the redesigned signal peptide was functional.