Apoptosis,
an important form of programmed cell death (PCD), is
a tightly regulated cellular process to eliminate unwanted or damaged
cells. Resistance of apoptosis is a hallmark of cancer cells. Inhibitor
of apoptosis proteins (IAPs) is a class of key apoptosis regulators
that promote cancer cell resistant to apoptosis, particularly in cancer
treatment. Disrupting the binding of IAPs with their functional partners
therefore is a promising strategy to restore the apoptotic response
to proapoptotic stimuli, particularly those introduced by standard
cancer therapies. The most successful example is the use of small
molecules to mimic the IAP-binding motif of an endogenous IAP antagonist,
second mitochondria-derived activator of caspase (SMAC). Here we will
review the functions of IAPs, the structural interactions of IAPs
with SMAC, four generations of SMAC-mimetic IAP antagonists, and representative
antagonists in clinical evaluations, focusing on research articles
over the past 15 years. Outlooks and perspectives on the associated
challenges are provided as well.
Prunella vulgaris L. is as a major plant in the Chinese traditional functional beverage Guangdong herbal tea for the treatment of fevers, diarrhea, and sore mouth. In this study, ethyl acetate parts of aqueous extracts from P. vulgaris L. (EtOAc-APV) were found to demonstrate potent acetylcholinesterase (AChE) inhibition in vitro. Therefore, this study was designed to further investigate the effects of EtOAc-APV on scopolamine (SCOP)-induced aging rats. Male Wistar rats were randomly divided into four groups (n = 12) and given orally by gavage EtOAc-APV (100 mg/kg) for 3 weeks. SCOP (1 mg/kg, ip) was administered to rats 30 min before starting behavioral tests consecutively for 3 days. EtOAc-APV could attenuate SCOP-induced brain senescence in rats by improving behavioral performance and decreasing brain cell damage, which was associated with a notable reduction in AChE activity and MDA level, as well as an increase in SOD and GPx activities. Additionally, EtOAc-APV administration could reduce the expression of NF-κB and GFAP, which showed an anti-neuroinflammatory effect on the SCOP-treated rat. Overall, the current study highlights P. vulgaris L. as an antidementia dietary supplement.
Polymer-based fluorescent nanomaterials have proven to universally image various tumors based on their extremely sharp responsiveness to pH change. Such a property has never been realized in supramolecular systems. We herein design a small molecule (DPP-thiophene-4) that is composed of a diketopyrrolopyrrole (DPP) core and two alkyl chains terminated with quaternary ammonium. DPP-thiophene-4 can self-assemble into a nonfluorescent nanoassembly when the pH is >7.0 but reversibly disassembles back to fluorescent monomers when the pH is <6.8. Meanwhile, its fluorescence emission increases by 10-fold within a 0.2 pH unit change. Such a fluorogenic nanoassembly can precisely differentiate a number of malignant tumors among normal tissues in vivo due to the slight acidity within tumor microenvironments. Further the nanoassembly shows satisfactory biocompatibility and an effective clearance from the body. Overall, this supramolecular fluorogenic nanoassembly exhibits an immense potential for realizing broad range tumor diagnosis.
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.