Efficacy and Safety of Woohwangchungsimwon Combined with Donepezil in Behavioral and Psychological Symptoms of Dementia in Patients with Probable Alzheimer's Disease: Study Protocol for a Randomized Controlled Trial.

Behavioral and psychological symptoms of dementia are a major factor in the burden of care and medical expenses. Conventional pharmacological treatments do not exert a distinct effect on the benefits versus the risks. The herbal medicine woohwangchungsimwon is frequently prescribed for neuropsychiatric disorders. An effect of woohwangchungsimwon on behavioral and psychological symptoms of dementia has been previously reported; however, no clinical studies have been conducted. We aim to evaluate the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating these symptoms in probable Alzheimer's disease. In this randomized, assessor-blinded, parallel-group clinical trial, 74 participants with probable Alzheimer's disease will be divided via block randomization into a woohwangchungsimwon + donepezil combination group (n = 37) or a donepezil single group (n = 37). Participants will include patients under donepezil treatment for at least a month. We will perform the study for 24 weeks. The Neuro-Psychiatric Inventory subscale scores will be the primary outcome. Secondary outcomes will include cognitive function, dementia severity, physical function, quality of life, depression, anxiety, and insomnia. For safety evaluation, we will assess adverse reactions, measure vital signs, and conduct laboratory tests. This is the first trial aiming to confirm the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating behavioral and psychological symptoms of dementia. Its findings could provide a basis for their co-administration to control these symptoms in probable Alzheimer's disease.

Preclinical study to improve microbubble-mediated drug delivery in cancer using an ultrasonic probe with an interchangeable acoustic lens.

Focused ultrasound with microbubbles (FUS-MBs) has shown that it can lead to an efficient drug delivery system (DDS) involving the oscillation and destruction of the MB but is limited in drug delivery due to its narrow pressure field. However, unfocused ultrasound with MBs (UUS-MBs) and an interchangeable acoustic lens can tune and enhance the pressure field for MB destruction to overcome the disadvantages of FUS-MB DDSs. We designed a lens suitable for an ultrasound-phased array probe and studied the optimal treatment conditions for MB destruction in vitro through an optical imaging setup. The DDS effects were evaluated in a rat hepatoma model using doxorubicin (DOX) treatment. A concave lens with a radius of curvature of 2.6 mm and a thickness of 4 mm was selected and fabricated. UUS-MBs with the acoustic lens at 60 Vpp for 32 cycles and a PRF of 1 kHz could induce MB destruction, promoting the DDS even under fluidic conditions. In the animal experiment, the UUS-MBs in the acoustic lens treatment group had a higher concentration of DOX in the tumor than the control group. Our system suggests uses an acoustic lens to increase DDS effectiveness by providing sufficient ultrasound irradiation to the MBs.

Resveratrol inhibits inflammation induced by heat-killed Listeria monocytogenes.

Resveratrol is a polyphenolic compound in red wine that has antioxidant and cardioprotective effects in animal models. Listeria monocytogenes is a pathogen that mainly affects immunocompromised individuals and is initially detected at the cell surface or in phagosomes by toll-like receptor 2. Many antioxidants also exert anti-inflammatory activities; therefore, we evaluated the anti-inflammatory properties of resveratrol by studying the various inflammatory responses induced by heat-killed L. monocytogenes (HKLM). Resveratrol strongly blocked HKLM-induced NADPH oxidase-1 mRNA and reactive oxygen species production by macrophages. Resveratrol also suppressed monocyte chemotactic protein-1 expression, cyclooxygenase-2 expression, prostaglandin production, inducible nitric oxide (NO) synthase expression, and NO production induced by HKLM. We investigated the signaling pathway involved in the resveratrol effect. HKLM stimulated glycogen synthase kinase 3ß (GSK3ß) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. The involvement of GSK3ß and ERK1/2 was tested using inhibitors. While the GSK3ß inhibitor LiCl potentiated the effect of HKLM, the MEK inhibitor U0126 blocked these responses. Additionally, pretreatment with resveratrol blocked phosphorylation of both kinases induced by HKLM. These results suggest that HKLM is strong inducer of inflammatory mediators, and that the inhibitory effect of resveratrol may be mediated by the GSK3ß and ERK1/2 pathways.