Sonodynamic Therapy: Advances and Challenges in Clinical Translation

Sonodynamic therapy (SDT) consists of the synergetic interaction between ultrasound and a chemical agent. In SDT, the cytotoxicity is triggered by ultrasonic stimuli, notably through cavitation. The unique features of SDT are relevant in the clinical context more than ever: the need for efficacy, accuracy, and safety while being noninvasive and preserving the patient's quality of life. However, despite the promising results of this technique, only a few clinical reports describe the use of SDT. The objective of this article is to provide an extensive overview of the clinical and preclinical research conducted in vivo on SDT, to identify the limitations, and to detail the developed strategies to overcome them.     

Generalized,severe epidermolysis bullosa simplex caused by a Keratin 5 p.E477K mutation

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease.     

Antidiabetic activity of Helicteres angustifolia root

Context The root of Helicteres angustifolia L. (Sterculiaceae) has been used as folk herbal drug to treat cancer, bacterial infections, inflammatory, and flu in China. However, there is no report on its antidiabetic activity.

Objective This study evaluates the antidiabetic activity of ethanol extract from H. angustifolia root.

Materials and methods The promoting effect of H. angustifolia root ethanol extract (25, 50, and 100 μg/mL) on glucose uptake was evaluated using HepG2 cell, differentiated C2C12 myotubes, and differentiated 3T3-L1 adipocytes. The antidiabetic activity of the extract was assessed in vivo using STZ-induced diabetic rats by orally administration of the extract (200 and 400?mg/kg b.w.) once per day for 28 d. Blood glucose, TG, TC, TP, HDL-C, UA, BUN, AST, ALT, insulin, and HOMA-IR were analyzed.

Results The results showed that the extract increased glucose uptake in C2C12 myotubes and 3T3-L1 adipocytes with an IC₅₀ value of 79.95 and 135.96 μg/mL, respectively. And about 12%, 19%, and 10% (p < 0.05) in HepG2 cells when compared with the control at the concentration of 25, 50, and 100 μg/mL, respectively. After 28 days’ treatment with the extract, significant reduction was observed in blood glucose, HOMA-IR, TC, TG, UA, BUN, AST, and ALT levels, while the levels of TP and HDL cholesterol increased.

Discussion and conclusion These results suggest that H. angustifolia root ethanol extract possess potent antidiabetic activity, which is the first report on antidiabetic activity of this plant.     

Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.