New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis, several of which are currently in clinical trials. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis.
Interlayer surfaces of layered double hydroxide (LDH) have been functionalized with amine moieties by condensation between the hydroxyl groups and (3‐aminopropyl)triethoxysilane (APS) molecules via the covalent oxane bonds M‐O‐Si (M=Zn and Cr) (see Figure). Since the galleries of the modified LDHs have a hydrophobic field, various functional molecules such as enzymes, catalysts, and organic molecules can be incorporated between the LDH layers.
Prior research on gerontology and housing has frequently adopted a perspective that aging-in-place is the "goal." Despite these meaningful results and policy implications, opportunities to explore consequences of aging-in-place, such as the association of this with overall well-being, have been overlooked. This study aims to fill this gap by investigating perceptions of well-being that could act as a driver or result of aging-in-place. With a nationwide random sample of non-Hispanic White, older individuals (60+), living in their homes ( N = 328), three segments of senior residents based on their reasons for aging-in-place were identified. Results reinforce the importance of community-based integrative programs and policies by indicating that the three identified clusters were not homogeneous; however, inclusive community-based supports and services can provide what each cluster needs to successfully age-in-place. Discussion provides a perspective on how to support successful aging-in-place, including the role of the federal government in funding and legislation.
One of the potential causes of age-related neuronal damage can be reactive oxygen species (ROS), as the brain is particularly sensitive to oxidative damage. In the present study, we investigated the effects of aging and dietary restriction (DR) on ROS generation, lipid peroxidation, and antioxidant enzymes in cerebrum, hippocampus, and cerebellum of 6-, 12-, 18-, and 24-month-old rats. ROS generation significantly increased with age in cerebrum of ad libitum (AL) rats. However, no significant age-difference was observed in hippocampus and cerebellum. DR significantly decreased ROS generation in cerebrum and cerebellum at 24-months. On the other hand, the increased lipid peroxidation of AL rats during aging was significantly reduced by DR in all regions. Our results further showed that catalase activity decreased with age in cerebellum of AL rats, which was reversed by DR, although SOD activity had little change by aging and DR in all regions. In a similar way, glutathione (GSH) peroxidase activity increased with age in cerebrum of AL rats, while DR suppressed it at 24-months. These data further support the evidence that the vulnerability to oxidative stress in the brain is region-specific.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.