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Replication
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
A similar effect of the protein synthesis inhibitors on the viral RNA accumulation was observed in all phages under study, including maturation protein, coat protein, and double maturation and coat amber mutants, where the replicase was the only synthesized phage protein in non-suppressor cells. This indicated that the excess of the replicase itself may be capable of suppression of the replicase and then RNA synthesis in the absence of coat protein. The prolongation of the replicase synthesis was always followed by the prolonged synthesis of RNA minus strands in all cases. Moreover, both replicase and RNA minus strands were formed in nearly equal amounts when protein synthesis was partially inhibited. Therefore, the observed coupling of both replicase and minus-strand RNA synthesis offered a possibility for full control over viral RNA replication by means of control of the replicase synthesis on the translational level, assuming the functional instability and relatively short half-life of the phage RNA plus and minus strands (Pumpen et al. 1978a, 1982).
Disposition and Metabolism of Drugs of Dependence
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
Although synthesis of new RNA and protein in brain of experimental animals has been shown to be an essential feature of the development of tolerance to morphine,495 it is not yet certain whether the enzyme induction and synthesis of protein in the CNS is really involved in the development of physical dependence and tolerance in humans. Furthermore, protein synthesis inhibitors used in such studies on experimental animals are known to have many other direct and indirect effects on CNS, apart from the inhibition of protein synthesis.
Toxoplasma
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Fernanda Silva de Souza, Renato Augusto DaMatta
These drugs act blocking the synthesis of tetrahydrofolate and interfere negatively in the nucleic acid synthesis by T. gondii. However, this combination is toxic to host cells and disturbs folic acid biosynthesis. Therefore, folinic acid is administered in association with these drugs.164 Other treatments include protein synthesis inhibitors, such as spiramycin,18 clindamycin, and clarithromycin.164
Current and emerging drug treatment strategies to tackle invasive community-associated methicillin-resistant Staphylococcus aureus (MRSA) infection: what are the challenges?
Published in Expert Opinion on Pharmacotherapy, 2023
Antonio Vena, Nadia Castaldo, Laura Magnasco, Martina Bavastro, Alessandro Limongelli, Daniele Roberto Giacobbe, Matteo Bassetti
It is well known, from in vitro analysis, that some antibiotics might significantly influence PVL production. For example, clindamycin and linezolid are important inhibitors of protein synthesis, and therefore rapidly inhibit PVL synthesis. Noteworthy, both linezolid and clindamycin have been found to enhance the susceptibility of MRSA to phagocytosis by human neutrophils, and to directly suppress the production of MRSA virulence factors, including PVL [69,70]. In this sense, the adjunctive protein synthesis inhibitor antibiotic treatment for serious infections produced by CA-MRSA always points to its greater efficacy. For example, in patients with skin abscess, the concomitant administration of clindamycin with vancomycin has been associated with an 18% reduction in the length of hospital stay as well as lower 90-day readmission [71].
Addressing the challenges with bacterial vaginosis pharmacotherapy
Published in Expert Opinion on Pharmacotherapy, 2023
Due to the lack of understanding of the mechanisms involved in BV development, current treatment is directed toward the alleviation of symptoms through reduction of BV-associated bacteria overgrowth and restoration of normal vaginal microbiota [5]. The first-line antibiotics used to treat BV are metronidazole (a DNA replication inhibitor) or clindamycin (a protein synthesis inhibitor) [11]. As recently reviewed, the recommended treatment regimens include 500 mg of metronidazole orally, twice a day for 7 days or in alternative an intravaginal application of 5 g of a gel containing 0.75% metronidazole, once a day, for 5 days. Because several side effects are associated with metronidazole therapy, such as nausea, vomiting, and gastrointestinal complaints, there is also the recommendation to use an intravaginal application of 5 g cream containing 2% of clindamycin, at bedtime, for 7 days. Alternative regimens include oral tinidazole and oral clindamycin [12]. Despite some evidence of sexual transmission and clinician recommendations to treat both the women with BV and her male partner [13], current antimicrobial treatment is only recommended for women with cases of symptomatic BV [14]. Furthermore, alternative regimens are being pursued, focused on either increasing treatment duration or drug concentration, as recently reviewed [12].
Stabilization of Nrf2 leading to HO-1 activation protects against zinc oxide nanoparticles-induced endothelial cell death
Published in Nanotoxicology, 2021
Longbin Zhang, Liyong Zou, Xuejun Jiang, Shuqun Cheng, Jun Zhang, Xia Qin, Zhexue Qin, Chengzhi Chen, Zhen Zou
We further explored the possible mechanisms for Nrf2 activation caused by ZnONPs. The mRNA expression of Nrf2 in HUVEC cells with or without ZnONPs treatment was determined. qPCR analysis results showed that ZnONPs treatment did not induce a significant change in the mRNA expression level of Nrf2 (Figure 6(A,B)), indicating that activation of Nrf2 did not occur at the transcriptional level. We then treated HUVEC cells with Z-Leu-Leu-Leu-al (MG-132), a potent proteasome inhibitor, prior to ZnONPs treatment. The western blot analysis results showed that MG132 dampened the ubiquitylation of Nrf2, indicating that the degradation of Nrf2 was dependent on the ubiquitin-proteasome pathway (Figure 6(C)). The protein synthesis inhibitor cycloheximide (CHX) was used to block protein synthesis to evaluate the degradation of protein. Under physiological conditions, Nrf2 is quickly degraded through the ubiquitin-proteasome pathway. However, we found that ZnONPs caused profound elevation of Nrf2 expression and slowed degradation of Nrf2 (approximately 9 h for the degradation of Nrf2 in the ZnONPs-treated HUVEC cells pretreated with CHX) (Figure 6(D)). Consistently, our results also illustrated that the total ubiquitination level was highly increased in response to ZnONPs treatment in a dose- and time-dependent manner (Figure 6(E,F)). Immunofluorescence analysis also demonstrated the elevation of ubiquitin in response to ZnONPs treatment (Figure 6(G)). Together, these results indicate that ZnONPs likely induce nonclassical activation of Nrf2 by dampening the degradation system.