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.

Hydrogen peroxide initiates oxidative stress and proteomic alterations in meningothelial cells.

Meningothelial cells (MECs) are fundamental cells of the sheaths covering the brain and optic nerve, where they build a brain/optic nerve-cerebral spinal fluid (CSF) barrier that prevents the free flow of CSF from the subarachnoid space, but their exact roles and underlying mechanisms remain unclear. Our attempt here was to investigate the influence elicited by hydrogen peroxide (H2O2) on functional changes of MECs. Our study showed that cell viability of MECs was inhibited after cells were exposed to oxidative agents. Cells subjected to H2O2 at the concentration of 150 µM for 24 h and 48 h exhibited an elevation of reactive oxygen species (ROS) activity, decrease of total antioxidant capacity (T-AOC) level and reduced mitochondrial membrane potential (ΔΨm) compared with control cells. 95 protein spots with more than twofold difference were detected in two dimensional electrophoresis (2DE) gels through proteomics assay following H2O2 exposure for 48 h, 10 proteins were identified through TOF/MS analysis. Among the proteomic changes explored, 8 proteins related to energy metabolism, mitochondrial function, structural regulation, and cell cycle control were downregulated. Our study provides key insights that enhance our understanding of the role of MECs in the pathology of brain and optic nerve disorders.

Hypobaric hypoxia triggers pyroptosis in the retina via NLRP3 inflammasome activation.

Hypobaric hypoxia initiates multiple impairment to the retina and is the major cause contributing to retinal function deficits such as high altitude retinopathy. However, the underlying molecular mechanism has not been clearly defined so far and remains to be clarified. In the present study, we have undertaken an approach to mimic 5000 m altitude with a low-pressure oxygen cabin and evaluated if pyroptosis is involved in the mechanisms by which hypobaric hypoxia triggers retinal impairment. We also used Radix Astragali seu Hedysari Compound (RAHC) to determine whether RAHC is capable of exerting protective effects on the hypobaric hypoxia-induced retinal dysfunction. We found that hypobaric hypoxia stress activated inflammasome complex through increasing NOD-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) protein levels. The protein expression of gasdermin-D, a master executor of pyroptosis, and NADPH oxidase 4, which is regarded as a main generator of reactive oxygen species (ROS), also elevated upon hypobaric hypoxia exposure. In addition, hypobaric hypoxia induced a significant increase in pro-inflammatory cytokines expression including interleukin-1ß and interleukin-18 in the rat retina. Our results indicate that hypobaric hypoxia initiates pyroptosis in the rat retina. RAHC attenuates hypobaric hypoxia-triggered retinal pyroptosis via inhibiting NLRP3 inflammasome activation and release of pro-inflammatory cytokines. The involvement of pyroptosis pathway in the retina in response to hypobaric hypoxia supports a novel insight to clarify the pathogenesis of hypobaric hypoxia-induced retinal impairment and provides a feasibility of inflammasome modulation for preserving retinal function.

Hesperidin ameliorates hypobaric hypoxia-induced retinal impairment through activation of Nrf2/HO-1 pathway and inhibition of apoptosis.

High-altitude retinopathy is initiated by hypobaric hypoxia and characterized by retinal functional changes, but the precise cellular and molecular mechanisms that mediate this dysfunction remain unclear. The aim of our investigation is to determine the protective efficacy of hesperidin (HSD) on the hypobaric hypoxia-induced damage to the retina. Experiment rats were randomly grouped as the control, hypobaric hypoxia group and HSD intervention group. The hypobaric hypoxia and the HSD intervention groups were maintained in a low-pressure oxygen cabin. We found that hypobaric hypoxia dramatically reduced nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) levels, induced an elevation in immunostaining of TUNEL-positive cells. Hypobaric hypoxia exposure resulted in the increase of Bcl-2, decrease of caspase3 and caspase9 expression as well as Bax level. HSD protected the retina from hypobaric hypoxia-caused impairment by enhancing Nrf2 and HO-1 activation, attenuating apoptotic caspases levels, and reducing Bax and preserving Bcl-2 expression. Additionally, oxidative stress increased poly (ADP-ribose) polymerase 1 (PARP1) and suppressed ciliary neurotrophic factor (CNTF) level, HSD treatment reverted this effect by down-regulation of PARP1 and up-regulation of CNTF expression. Taken together, our findings implicate that HSD exerts a protective role in response to hypobaric hypoxia stress by activating Nrf2/HO-1 pathway and inhibiting apoptosis.

Multitarget stool DNA test compared with fecal occult blood test for colorectal cancer screening.

Patient screening is important for early diagnosis of colorectal cancer (CRC). The present study aimed to compare the multitarget stool DNA (mt-sDNA) test with the fecal occult blood test (FOBT) for CRC screening. A total of 151 individuals were screened using colonoscopy, mt-sDNA and FOBT for the detection of CRC and adenoma. The results of the mt-sDNA test and FOBT were compared with colonoscopy to examine their sensitivity and specificity. Subsequently, the sensitivity and specificity of the mt-sDNA test were compared with those of FOBT in CRC and large adenoma. Stool samples were collected from patients with CRC (n=50) or large adenoma (n=51), as well as from normal controls (n=50). The mt-sDNA test outperformed FOBT in detecting CRC with a sensitivity of 90.0% (45/50) vs. 42.0% (21/50), advanced adenoma with a sensitivity of 70.6% (36/51) vs. 19.6% (10/51), stage I-III CRC with a sensitivity of 91.9% (34/37) vs. 29.7% (11/37), and stage IV CRC with a sensitivity of 84.6% (11/13) vs. 76.9% (10/13). In addition, the mt-sDNA test exhibited a specificity of 94.0% (47/50) in detecting CRC, which was superior to FOBT with a specificity of 90.0% (45/50). Therefore, the mt-sDNA test may have higher sensitivity and specificity compared with FOBT in diagnosing both CRC and advanced adenoma.

Effects of Hypobaric Hypoxia on Rat Retina and Protective Response of Resveratrol to the Stress.

High-altitude retinopathy represents retinal functional changes associated with environmental challenges imposed by hypobaric hypoxia, but the detailed cellular and molecular mechanism underlying this process remains unclear. Our current investigation was to explore the effect of hypobaric hypoxia on the rat retina and determine whether resveratrol has a protective efficacy on the hypoxic damage to the retina. Experiment rats were randomly grouped as the control group, hypoxia group and resveratrol intervention group. The hypoxia group and the resveratrol intervention group were maintained in a low-pressure oxygen cabin, and the resveratrol intervention group was given daily intraperitoneal injections with resveratrol. We found that hypobaric hypoxia increased thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2) expression in retinas, and resveratrol treatment significantly reversed these changes (P < 0.05, P < 0.05 respectively). In comparison with controls, hypoxia upregulated the mRNA expression levels of caspase3 (P < 0.001), caspase9 (P < 0.01), heat shock protein 70 (Hsp70) (P < 0.05), heat shock protein 90 (Hsp90) (P < 0.001) and hypoxia-inducible factor-1 (HIF-1) (P < 0.05). Resveratrol administration caused a significant decrease in the gene expression of caspase3 (P< 0.001), HSP90 (P < 0.05) and HIF-1 mRNA (P < 0.01) as well as an increase in HSP70 mRNA when compared with the hypoxia group. These findings indicated that resveratrol exerted an anti-oxidative role by modulating hypoxia stress- associated genes and an anti-apoptosis role by regulating apoptosis-related cytokines. In conclusion, hypobaric hypoxia may have a pathological impact on rat retinas. The intervention of resveratrol reverses the effect induced by hypobaric hypoxia and elicits a protective response to the stress.

Meningothelial cells react to elevated pressure and oxidative stress.

BACKGROUND: Meningothelial cells (MECs) are the cellular components of the meninges enveloping the brain. Although MECs are not fully understood, several functions of these cells have been described. The presence of desmosomes and tight junctions between MECs hints towards a barrier function protecting the brain. In addition, MECs perform endocytosis and, by the secretion of cytokines, are involved in immunological processes in the brain. However, little is known about the influence of pathological conditions on MEC function; e.g., during diseases associated with elevated intracranial pressure, hypoxia or increased oxidative stress. METHODS: We studied the effect of elevated pressure, hypoxia, and oxidative stress on immortalized human as well as primary porcine MECs. We used MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) bioreduction assays to assess the proliferation of MECs in response to treatment and compared to untreated control cells. To assess endocytotic activity, the uptake of fluorescently labeled latex beads was analyzed by fluorescence microscopy. RESULTS: We found that exposure of MECs to elevated pressure caused significant cellular proliferation and a dramatic decrease in endocytotic activity. In addition, mild oxidative stress severely inhibited endocytosis. CONCLUSION: Elevated pressure and oxidative stress impact MEC physiology and might therefore influence the microenvironment of the subarachnoid space and thus the cerebrospinal fluid within this compartment with potential negative impact on neuronal function.

Primary cell culture of meningothelial cells--a new model to study the arachnoid in glaucomatous optic neuropathy.

BACKGROUND: In a previous report, we found that the occurrence and amount of meningothelial cell nests in the subarachnoid space are significantly increased in glaucomatous optic nerves compared to normals. In order to allow research into the role of meningothelial cells during diseases of the optic nerve, an in vitro model is necessary. For this purpose, we developed a culture method for porcine meningothelial cells from the arachnoid layer covering the optic nerve. METHODS: Meningothelial cells were scraped from the arachnoid layer of porcine optic nerves and cultured for 2-3 weeks until the cells formed a monolayer. To eliminate contaminating fibroblasts from the culture, cells were negatively selected using magnetic anti-fibroblast beads after the first passage. Cells were detached using 0.05% Trypsin-EDTA, incubated with anti-fibroblast beads, separated using a magnetic column and the flow-through was collected. The purified primary meningothelial cells were characterized by electron microscopy and immunocytochemistry using anti-glial fibrillary acidic protein (GFAP) and anti-keratan sulfate antibodies. RESULTS: Primary cells grew out after dissection and formed a monolayer within 2-3 weeks, which was composed of two morphologically different cell types, flattened cells with round nuclei and fibroblast-like cells with long processes. The fibroblast-like cells in the culture could be labelled and selected using anti-fibroblast microbeads. The second cell type did not bind to the anti-fibroblast beads, and upon immunocytochemistry showed a marked expression of both GFAP and keratan sulphate. In addition, examination of these cells by electron microscopy revealed morphological characteristics of meningothelial cells, including hemidesmosomes and cytoplasmatic filaments. CONCLUSIONS: The technique described in this paper for the primary culture of meningothelial cells from the subarachnoid space of the optic nerve and using magnetic beads for the removal of fibroblasts is effective in obtaining a highly enriched meningothelial cell culture.

L-PGDS (betatrace protein) inhibits astrocyte proliferation and mitochondrial ATP production in vitro.

L-PGDS is the most abundant protein present in the cerebrospinal fluid (CSF). Although CSF was believed to be homogenous in content, a previous study has showed that a marked concentration gradient of L-PGDS exists between the spinal CSF and the CSF in the subarachnoid space of patients with optic nerve disease (papilledema and normal-tension glaucoma). Astrocytes play a critical role in maintaining the integrity of axon function in the central nervous system and specifically in the optic nerve, and we therefore investigated the biochemical effects of L-PGDS on the proliferation of astrocytes and on the production of adenosine triphosphate (ATP) by astrocyte mitochondria. We found an inhibitory effect of L-PGDS on both proliferation of astrocytes and production of astrocyte ATP. The concentrations that inhibited astrocyte proliferation and ATP production were in the range measured in patients with idiopathic intracranial hypertension and in patients with normal-tension glaucoma. As the CSF is in contact with axons and mitochondria of the optic nerve (Bristow et al. Archives of Ophthalmology, 120, 791-796, 2002), we postulate that a change in the concentration of CSF protein such as L-PGDS could exercise a harmful effect on these structures.

Septin expression in proliferative retinal membranes.

We undertook this study to evaluate the expression of septin family members SEPT5, SEPT8, and SEPT11 in proliferative retinal membranes. Epiretinal membranes (ERM) were obtained from seven patients with proliferative vitreoretinopathy (PVR) and from four patients and four postmortem eyes with proliferative diabetic retinopathy (PDR). Subretinal membranes (SRM) were obtained from one patient and six postmortem eyes. Membranes were examined by immunohistochemical staining of paraffin sections using polyclonal antibodies against SEPT5, SEPT8, and SEPT11 and an ABC detection system. SEPT8 expression was detected in all ERM and SRM, with an exceptionally strong expression of 100% for ERM of PVR, 63% for PDR membranes, and 57% for SRM. SEPT11 was identified in 91% of all cases, with strong expression of 14%, 25%, and 14% in ERM of PVR, PDR, and SRM, respectively. SEPT5 was seen in 54% of all cases; strong immunostaining was found in only one case of PVR membranes. Our finding suggests a role for members of the septin family in the development of proliferative retinal membranes.