New modalities providing safe and effective treatment of pain, especially prolonged pathological pain, have not appeared despite much effort. In this mini-review/overview we suggest that new paradigms of drug design are required to counter the underlying changes that occur in the nervous system that may elicit chronic pain states. We illustrate this approach with the example of designing, in a single ligand, molecules that have agonist activity at mu and delta opioid receptors and antagonist activities at cholecystokinin (CCK) receptors. Our findings thus far provide evidence in support of this new approach to drug design. We also report on a new biophysical method, plasmon waveguide resonance (PWR) spectroscopy, which can provide new insights into information transduction in G-protein coupled receptors (GPCRs) as illustrated by the delta opioid receptor.
Traditional microneedle (MN) technology offers unique advantages in treating wound infections; however, its single-function design lacks the capability for real-time monitoring of wound conditions, often resulting in uncontrolled drug release. Herein, an anti-infective and intelligent MN patch (SP-CSMN) integrating three functional modules is developed, including temperature monitoring, Bluetooth wireless communication, and responsive drug release. The patch employed chitosan (CS) as a porous substrate, filled with temperature-sensitive poly(N-isopropylacrylamide) (PNIPAM) to encapsulate and release the antibiotic rifampicin.
Background: Elinzanetant is a dual neurokinin-1,3 receptor antagonist in development for the treatment of menopausal vasomotor symptoms. The objectives of these studies were to characterize the mass balance and biotransformation of elinzanetant.
Methods: In the clinical evaluation, whole blood, plasma, urine, and feces were collected from healthy fasted male volunteers (n = 6) following a single dose of 120 mg [C]-elinzanetant oral suspension for analysis of total radioactivity and metabolite profiling.
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Urology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Cisplatin (CDDP) resistance has been established to significantly impact Bladder Cancer (BCa) therapy. On the other hand, the crucial regulatory involvement of SIRT7 and EZH2 in bladder cancer development is well known. Herein, the collaborative regulatory roles and underlying mechanisms of SIRT7 and EZH2 in CDDP resistance in bladder cancer were explored.
Objectives: The objectives of the study are to investigate infection risk in offspring born to women with systemic lupus erythematosus (SLE) compared with offspring born to women without SLE and examine the mediating role of preterm birth.
Design: This is a register-based cohort study.
Setting: Liveborn singletons born in Sweden, 2006-2021, were included in the study.
Introduction: Chronic pain is one of the most common and serious symptoms of cancer. Despite the limitations of dose titration using only one type of opioid, the effects of opioid combinations are poorly understood.
Methods And Analysis: This study will be conducted in accordance with the Cochrane Handbook of Systematic Reviews of Interventions 6.
