A wireless battery-free eye modulation patch for high myopia therapy.

The proper axial length of the eye is crucial for achieving emmetropia. In this study, we present a wireless battery-free eye modulation patch designed to correct high myopia and prevent relapse. The patch consists of piezoelectric transducers, an electrochemical micro-actuator, a drug microneedle array, µ-LEDs, a flexible circuit, and biocompatible encapsulation. The system can be wirelessly powered and controlled using external ultrasound. The electrochemical micro-actuator plays a key role in precisely shortening the axial length by driving the posterior sclera inward. This ensures accurate scene imaging on the retina for myopia eye. The drug microneedle array delivers riboflavin to the posterior sclera, and µ-LEDs' blue light induces collagen cross-linking, reinforcing sclera strength. In vivo experiments demonstrate that the patch successfully reduces the rabbit eye's axial length by ~1217 µm and increases sclera strength by 387%. The system operates effectively within the body without the need for batteries. Here, we show that the patch offers a promising avenue for clinically treating high myopia.

Ferroptosis: underlying mechanisms and involvement in neurodegenerative diseases.

Ferroptosis, a mode of cell death that was recently identified in 2012, is driven by iron-dependent lipid peroxidation and distinct from other mechanisms of cell death such as autophagy and apoptosis. Ferroptosis has the unique features of disruptions in iron equilibrium, iron-induced lipid peroxidation, and the accumulation of glutamate-induced cellular toxicity. The regulation of ferroptosis mainly involves the iron, lipid, and amino acid metabolic pathways, which are controlled by system Xc-, voltage-dependent anion channels, p53 and other pathways. Neurodegenerative diseases involve gradual neuronal loss predominantly within the central nervous system and are categorized into both sporadic and rare hereditary disorders. These diseases result in the progressive decline of specific neuron populations and their interconnections. Recent investigations have revealed a strong correlation between the manifestation and progression of neurodegenerative diseases and ferroptosis. The pharmacological modulation of ferroptosis, whether by induction or inhibition, exhibits promising prospects for therapeutic interventions for these diseases. This review aims to examine the literature on ferroptosis and its implications in various neurodegenerative diseases. We hope to offer novel insights into the potential therapies targeting ferroptosis in central nervous system neurodegenerative diseases. However, there are still limitations of this review. First, despite our efforts to maintain objectivity during our analysis, this review does not cover all the studies on ferroptosis and neurodegenerative diseases. Second, cell death in neurodegenerative diseases is not solely caused by ferroptosis. Future research should focus on the interplay of different cell death mechanisms to better elucidate the specific disease pathogenesis.

Thermal damage and the prognostic evaluation of laser ablation of bone tissue-a review.

In recent years, an increasing number of scientists have focused on conducting experiments on laser ablation of bone tissue. The purpose of this study was to summarize the prognosis of tissue and the extent of thermal damage in past hard tissue ablation experiments, and review the evidence for the feasibility of laser osteotomy in surgery. An electronic search of PubMed, China National Knowledge Infrastructure (CNKI), and Web of Science (WOS) for relevant English-language articles published through June 2023 was conducted. This review includes 48 literature reports on laser ablation of hard tissues from medical and biological perspectives. It summarizes previous studies in which the ideal ablation rate, depth of ablation, and minimal damage to bone tissue and surrounding soft tissues were achieved by changing the laser type, optimizing the laser parameter settings, or adding adjuvant devices. By observing their post-operative healing and inflammatory response, this review aims to provide a better understanding of pulsed laser ablation of hard tissues. Previous studies suggest that laser osteotomy has yielded encouraging results in bone resection procedures. We believe that low or even no thermal damage can be achieved by experimentally selecting a suitable laser type, optimizing laser parameters such as pulse duration and frequency, or adding additional auxiliary cooling devices. However, the lack of clinical studies makes it difficult to conclusively determine whether laser osteotomy is superior in clinical applications.

Natural products: protective effects against ischemia-induced retinal injury.

Ischemic retinal damage, a common condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, and other eye diseases, threatens the vision of millions of people worldwide. It triggers excessive inflammation, oxidative stress, apoptosis, and vascular dysfunction, leading to the loss and death of retinal ganglion cells. Unfortunately, minority drugs are available for treating retinal ischemic injury diseases, and their safety are limited. Therefore, there is an urgent need to develop more effective treatments for ischemic retinal damage. Natural compounds have been reported to have antioxidant, anti-inflammatory, and antiapoptotic properties that can be used to treat ischemic retinal damage. In addition, many natural compounds have been shown to exhibit biological functions and pharmacological properties relevant to the treatment of cellular and tissue damage. This article reviews the neuroprotective mechanisms of natural compounds involve treating ischemic retinal injury. These natural compounds may serve as treatments for ischemia-induced retinal diseases.

Piperine ameliorates ischemic stroke-induced brain injury in rats by regulating the PI3K/AKT/mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Piperine (PIP), a main active component isolated from Piper nigrum L., exerts neuroprotective effects in a rat model of ischemic stroke (IS). However, studies on the effects of PIP on neuroprotection and autophagy after IS are limited. AIM OF THE STUDY: This study aimed to prove the protective effects of PIP against brain IS and elucidate its underlying mechanisms. MATERIALS AND METHODS: Specific pathogen-free male Sprague-Dawley rats were selected to establish a permanent middle cerebral artery occlusion model. The experiment was randomly divided into six groups: sham group, model group, PIP intervention group (10, 20, and 30 mg/kg group), and nimodipine group (Nimo group, 12 mg/kg). Neurological function score, postural reflex score, body swing score, balance beam test, and grip strength test were used to detect behavioral changes of rats. The area of cerebral infarction was detected by TTC staining, and the number and morphological changes of neurons were observed by Nissl and HE staining. In addition, the ultrastructure of hippocampal dentate gyrus neurons was observed using a transmission electron microscope. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway proteins and autophagy-related proteins, namely, Beclin1 and LC3, in the hippocampus and cortex. Cell experiments established an in vitro model of oxygen-glucose deprivation (OGD) with the HT22 cell line to verify the mechanism. The experiment was divided into five groups: control group, OGD group, OGD + PIP 20 µg/mL group, OGD + PIP 30 µg/mL group, and OGD + PIP 40 µg/mL group. CCK-8 was used to measure cell activity, and Western blot was used to measure the expression of PI3K/AKT/mTOR signaling pathway proteins and autophagy-related proteins (Beclin1 and LC3). RESULTS: Compared with the model group, the neurological function scores, body swing scores, and postural reflex scores of rats in the 10, 20, and 30 mg/kg PIP intervention groups and Nimo groups decreased, whereas the balance beam score and grip test scores increased (all p < 0.05). After 10, 20, and 30 mg/kg PIP and Nimo intervention, the cerebral infarction area of pMCAO rats was reduced (p < 0.01), and Nissl and HE staining results showed that the number of neurons survived in the 30 mg/kg PIP and Nimo intervention groups increased. Cell morphology and structure were significantly improved (p < 0.05). Most of the hippocampal dentate gyrus neurons and their organelles gradually returned to normal in the 30 mg/kg PIP and Nimo intervention groups, with less neuronal damage. The expression levels of p-mTOR, p-AKT, and p-PI3K in the hippocampus and cortex of the 30 mg/kg PIP and Nimo intervention groups decreased, whereas the expression level of PI3K increased (all p < 0.05). In addition, the expression level of autophagy-related proteins, namely, Beclin1 and LC3-II, in the 30 mg/kg PIP and Nimo intervention groups decreased (all p < 0.05). Results of CCK-8 showed that after 1 h of OGD, the 30 and 40 µg/mL PIP intervention groups had higher cell viability than the OGD group (p < 0.01). Western blot results showed that compared with the OGD group, the expression level of p-mTOR, p-AKT, and p-PI3K in the 30 and 40 µg/mL PIP intervention groups decreased, and the expression level of PI3K increased (all p < 0.05). Moreover, the expression level of autophagy-related proteins, namely, Beclin1 and LC3-II, in the 30 and 40 µg/mL PIP intervention groups decreased (all p < 0.05). CONCLUSIONS: This study shows that PIP is a potential compound with neuroprotective effects. PIP can inhibit the PI3K/AKT/mTOR pathway and autophagy. Its inhibition of autophagy is possibly related to modulating the PI3K/AKT/mTOR pathway. These findings provide new insights into the use of PIP for the treatment of IS and its underlying mechanism.

Dichloromethane extraction from Piper nigrum L. and P. longum L. to mitigate ischemic stroke by activating the AKT/mTOR signaling pathway to suppress autophagy.

Dichloromethane fraction (DF) of Piper nigrum L. and P. longum L. (PnL and PlL), has been found to exert a protective effect against ischemic stroke in rats. However, the regulatory mechanism exerted by PnL and PIL have not been fully elucidated. In this study, we found that DF greatly ameliorated cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion (pMCAO). The neurological score, behavioral assessment, brain infarct volume, phosphorylation of AKT (p-AKT), phosphorylation mTOR (p-mTOR), and Atg7 protein levels were determined. Additionally, we discovered that DF pretreatment reduced infarct volume, neurological score, and brain damage. Furthermore, DF therapy caused the downregulation of Atg7 and p-AKT expression, as well as the upregulation of p-mTOR expression. In conclusion, our findings indicated that DF treatment can reduce brain damage and inhibit apoptosis and autophagy by activating the Akt-mTOR signaling pathway in ischemic stroke.

Effect of Sox10 on remyelination of the hippocampus in cuprizone-induced demyelinated mice.

OBJECTIVE: The low number of oligodendrocytes (OLs) in the hippocampus of patients with schizophrenia suggests that hippocampal demyelination is changed in this condition. Sox10 is expressed throughout OL development. The effect of Sox10 on myelin regeneration is unknown. This study aimed to analyze changes in Sox10 expression in the hippocampus and its regulatory role in hippocampal myelin regeneration in a mouse model of demyelination. METHODS: Mice were fed 0.2% cuprizone (CPZ) for six weeks to establish the acute demyelinating model (CPZ mice). Behavioral changes of these mice were assessed via open field and tail suspension tests. The ultrastructure of the myelin sheaths in the hippocampus was observed by transmission electron microscopy. The expression levels of myelin sheath-related proteins and the transcription factor Sox10 were detected via immunohistochemistry and Western blots. Furthermore, Sox10-overexpressing adeno-associated virus was injected into the hippocampus after establishing the demyelinating model to investigate effects of Sox10 on remyelination. RESULTS: CPZ mice showed abnormal behavioral changes, a large number of pathological changes in the myelin sheaths, and significantly reduced protein expression of the myelin sheath markers myelin basic protein and proteolipid protein. This confirmed that the demyelinating model was successfully established. Meanwhile, the protein expression of the oligodendrocyte precursor cell marker neural/glial antigen 2 (NG2) increased, whereas Sox10 expression decreased. After Sox10 overexpression in the hippocampus, the abnormal behavior was improved, the ultrastructure of the myelin sheaths was restored, and the expression of myelin sheath protein was reversed. NG2 expression was upregulated. CONCLUSION: Overexpression of Sox10 promotes hippocampal remyelination after CPZ-induced acute demyelination.