Research progress on gas signal molecular therapy for Parkinson's disease.

The pathogenesis of Parkinson's disease (PD) remains unclear. Among the pathological manifestations is the progressive degeneration of the nigrostriatal dopaminergic pathway, leading to massive loss of neurons in the substantia nigra pars compacta and dopamine (DA) depletion. Therefore, the current drug treatment is primarily based on DA supplementation and delaying the progression of the disease. However, as patients' symptoms continue to worsen, the drug effect will gradually decrease or even disappear, thereby further aggravating clinical symptoms. Gas signaling molecules, such as hydrogen sulfide (H2S), nitric oxide (NO), carbon monoxide (CO), and hydrogen (H2), exhibit pleiotropic biological functions and play crucial roles in physiological and pathological effects. In common neurodegenerative diseases including Alzheimer's disease and PD, gas signal molecules can prevent or delay disease occurrence via the primary mechanisms of antioxidation, anti-inflammatory response, and antiapoptosis. This article reviews the therapeutic progress of gas signaling molecules in PD models and discusses the possibility of their clinical applications.

Delivery of hydroxycamptothecin via sonoporation: An effective therapy for liver fibrosis.

Hepatic fibrosis is the common pathway for most chronic liver diseases, characterized by excessive accumulation of extracellular matrix (ECM) proteins. It has been shown that fibrotic ECM significantly hindered passage of nanoparticles. Efforts have been made by decorating degrading enzymes on surfaces of nanosized delivery vehicles to improve drug delivery. However, these strategies are restricted by limiting shelf-life. Inspired by the application of sonoporation in assisting drug delivery through blood-brain barrier and tumor tissues, we investigated whether sonoporation can be an alternative strategy in improving drug delivery for fibrotic diseases. Hydroxycamptothecin (HCPT), a potential drug in treating liver fibrosis, was selected as a model drug to evaluate the drug delivery efficiency and therapeutic effect among three delivery strategies, i.e., (1) injection solution, (2) delivery through liposomes, and (3) delivery via sonoporation. Our study showed that in addition to the improved drug delivery efficiency, the combination of HCPT and sonoporation led to synergistic effect and the mechanisms were investigated. The treatment group of HCPT delivered with sonoporation achieved the most significant attenuation in liver fibrosis among the three delivery strategies.