Vincamine, an active constituent of Vinca rosea ameliorates experimentally induced acute lung injury in Swiss albino mice through modulation of Nrf-2/NF-κB signaling cascade.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the leading pulmonary inflammatory disorders causing significant morbidity and mortality. Vincamine is a novel phytochemical with promising anti-inflammatory properties. In the current work, the protective effect of vincamine was studied in vitro (Raw 264.7 macrophages) and in vivo against lipopolysaccharide (LPS) induced ALI in Swiss albino mice. Vincamine significantly reduced nitrite and TNF-α release from the LPS stimulated macrophages and increased the levels of IL-10, indicating potent anti-inflammatory effects. It was observed that vincamine at the dose of 40 mg/kg, significantly reduced LPS induced inflammatory cell count in blood and in bronchoalveolar lavage (BAL) fluid. Further, vincamine exerted potent suppression of inflammation by reducing the expression of proinflammatory cytokines, while significantly increased (p < 0.001) the expression of anti-inflammatory cytokine (IL-10 and IL-22). Interestingly, histological changes were reversed in vincamine treated groups in a dose-dependent manner. Immunohistochemical analysis revealed significantly enhanced expression of NF-κB, TNF-α and COX-2 while reduced expression of Nrf-2 in disease control group, which were significantly (p < 0.001) ameliorated by vincamine. We, to the best of our knowledge, report for the first time that vincamine possesses protective potential against LPS induced inflammation and oxidative stress, possibly by inhibiting the NF-κB cascade, while positively regulating the Nrf-2 pathway. These findings are of potential relevance for COVID-19 management concerning the fact that lung injury and ARDS are its critical features.

An interventional study on intensive care unit drug therapy assessment in a rural district hospital in India.

BACKGROUND: Intensive care unit is a potential area for drug-related problems. As many of the patients treated are complex patients, clinical pharmacy intervention could find drug therapy problems. MATERIALS AND METHODS: Drug information liaisons daily attended ward rounds with intensivists and screened the patient for drug therapy assessment using the American Society for Health-System Pharmacists clinical skills competition DTA format. This was a prospective study done for 6 months from August 2012 to January 2013. Simple statistics were used to tabulate the drug-related problems assessed. RESULTS: A total of 72 patients were screened for drug therapy problems, for which 947 drug doses were prescribed in the study period. The total number of prescriptions was 148. The average number of drugs per prescription was 6.39 and the average number of drugs per patient was 13.15. A total of 243 problems were identified; on an average, 1.67 problems were present per prescription. The total number of drug interactions identified was N = 192 (78.2%); majority of them (61.4%) were of type C (not serious). So, 55.73% of them were monitored and not stopped or substituted. The second type of problem was a correlation between drug therapy and medical problem (7.4%). Appropriate drug selection and drug regimen was the third problem, and the adverse drug reactions and therapeutic duplications accounted for approximately 2% of the drug-related problems identified. CONCLUSION: Drug interactions constituted the major problem of ICUs, but not many were serious or significant. Consensus in assessment of drug-related problems and convincing intensivists with good quality evidences are required for better acceptance of interventions.

An extended transcriptional regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs.

Recent studies of genome-wide transcriptional regulatory network (TRN) revealed several intriguing structural and dynamic features of gene expression at a system level. Unfortunately, the network under study is often far from complete. A critical question is thus how much the network is incomplete and to what extent this would affect the results of analysis. Here we compare the Escherichia coli TRN built by Shen-Orr et al. (Nature Genet., 31, 64-68) with two TRNs reconstructed from RegulonDB and Ecocyc respectively and present an extended E.coli TRN by integrating information from these databases and literature. The scale of the extended TRN is about twice as large as the previous ones. The new network preserves the multi-layer hierarchical structure which we recently reported but has more layers. More global regulators are inferred. While the feed forward loop (FFL) is confirmed to be highly representative in the network, the distribution of the different types of FFLs is different from that based on the incomplete network. In contrast to the notion of motif aggregation and formation of homologous motif clusters, we found that most FFLs interact and form a giant motif cluster. Furthermore, we show that only a small portion of the genes is solely regulated by only one FFL. Many genes are regulated by two or more interacting FFLs or other more complicated network motifs together with transcriptional factors not belonging to any network motifs, thereby forming complex regulatory circuits. Overall, the extended TRN represents a more solid basis for structural and functional analysis of genome-wide gene regulation in E.coli.