Elevated aldehyde dehydrogenase (ALDH) activity correlates with poor outcome for many solid tumors as ALDHs may regulate cell proliferation and chemoresistance of cancer stem cells (CSCs). Accordingly, potent, and selective inhibitors of key ALDH enzymes may represent a novel CSC-directed treatment paradigm for ALDH+ cancer types. Of the many ALDH isoforms, we and others have implicated the elevated expression of ALDH1A3 in mesenchymal glioma stem cells (MES GSCs) as a target for the development of novel therapeutics. To this end, our structure of human ALDH1A3 combined with in silico modeling identifies a selective, active-site inhibitor of ALDH1A3. The lead compound, MCI-INI-3, is a selective competitive inhibitor of human ALDH1A3 and shows poor inhibitory effect on the structurally related isoform ALDH1A1. Mass spectrometry-based cellular thermal shift analysis reveals that ALDH1A3 is the primary binding protein for MCI-INI-3 in MES GSC lysates. The inhibitory effect of MCI-INI-3 on retinoic acid biosynthesis is comparable with that of ALDH1A3 knockout, suggesting that effective inhibition of ALDH1A3 is achieved with MCI-INI-3. Further development is warranted to characterize the role of ALDH1A3 and retinoic acid biosynthesis in glioma stem cell growth and differentiation.

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Background The present study covered an assessment of methanolic acetate fractions of Pistia stratiotes , commonly known as water lettuce, for analgesic, anti‐inflammatory, and CNS depressant activities. Methods The methanol acetate fractions were extracted from Pistia stratiotes and administered to the experimental animals as 200 and 400 mg/kg doses to determine the effect on acetic acid‐induced writhing and formalin‐induced licking and biting, for the assessment of analgesic activity. The anti‐inflammatory assay was done using the carrageenan‐induced hind paw edema method, while assessment of CNS depressant activity was done using the open field and hole cross tests. The effects were compared to standard reference drugs. Results At both doses (200 and 400 mg/kg body weight), the methanolic acetate extract of P. stratiotes showed significant analgesic action ( P < 0.05) against acetic acid‐induced writhing. The extract was also found to give significant protection against licking and biting at both doses. The methanolic acetate extract of P. stratiotes showed a significant ( P < 0.05) anti‐inflammatory effect from 0 minutes up to 3 hours in the carrageenan‐induced paw edema test. In the CNS depressant assay, the methanolic acetate extract showed significant ( P < 0.05) depressant activity at both doses from 30 to 120 minutes in both the hole cross and open field tests. Conclusion Thus we can conclude that P. stratiotes extracts have significant analgesic, anti‐inflammatory, and CNS depressant activity, compared to standard compounds, in an animal model.

Background: Antimicrobial resistance poses a major threat in the treatment of respiratory disease especially in developing countries like Bangladesh. Multidrug-resistant (MDR) bacteria along with extremely drug resistant (XDR) bacteria have emerged as major clinical and therapeutic dilemma in the treatment of tracheal infections here. Thus, the aim of this study is to assess multidrug resistance among clinical strains isolated from tracheal aspirates of patients in Dhaka, Bangladesh.Methods: Total 200 clinical isolates from tracheal aspirates were identified and their antibiotic susceptibility profiles were evaluated by using the VITEK 2 system following the Clinical and Laboratory Standards Institute guidelines. Patient information on diagnosis, sex, age was obtained from hospital data.Results: Of 200 clinical isolates obtained, Pseudomonas aeruginosa was the most frequent pathogens (30.5%) followed by Acinetobacter baumannii (29%), Klebsiella pneumoniae (22.5%), Streptococcus pneumoniae (7.5%), Escherichia coli (5%), Staphylococcus aureus (2%), Proteus spp (1.5%), Enterobacter spp (1%), Citrobacter spp (0.5%), Providencia spp (0.5%). Of 20 different antibiotics tested, highest number of isolates (86%) showed resistance to third generation cephalosporin cefixime, however least number of isolates showed resistance to polymixin antibiotics- colistin (12.5%) and polymixin B (6%). Tracheal infection was found to be more prevalent in males rather than in females although this difference was not statistically significant. The prevalence of infections was highest among the patients of age-group (old adults) ≥60 years (61.5%). Of 200 clinical isolates, 43 (21.5%) were XDR and 125 (62.5%) were MDR bacteria. Of 200 clinical isolates, the synthesis of extended spectrum β-lactamases (ESBL) and carbepenemase were detected in 59 (29.5%) and 98 (49%) strains respectively.Conclusions: Tracheal infections caused by β-lactamase producing MDR and XDR pathogens among patients are high in Dhaka, Bangladesh. Therefore, there is an urgent need for constant surveillance and interventions in Bangladesh in order to prevent further spreading of those resistant organisms.