Retinal giant cyst treated by the scleral buckling procedure: A case report.

INTRODUCTION: Retinal cysts are rare lesions of the fundus that are essentially fluid-filled cavities located or originating in the retina, with a diameter larger than the normal retinal thickness. To date, there have been few case reports of giant retinal cyst hemorrhage with retinoschisis. CASE PRESENTATION: A 32-year-old woman with no other medical history complained of decreased vision for 3 days after a severe cough. The best-corrected visual acuity in the right eye was 0.5. A comprehensive ophthalmological examination including slit-lamp fundoscopy, ultrasound scan of the eye, optical coherence tomography scan, and orbital magnetic resonance imaging was performed. Ophthalmological examination revealed grade III anterior chamber blood cells and grade III vitreous hemorrhage in the right eye and a large herpetic cyst on the nasal side of the retina. The cyst projected into the vitreous, with a large amount of hemorrhage vaguely visible within it. The cyst was clearly visible, and a superficial retinal limiting detachment was observed around it. Ultrasound showed a retinal cyst with retinal detachment in the right eye. Laboratory test results were unremarkable. After 3 months of conservative treatment, the patient's intracystic hemorrhage was significantly absorbed, but the size of the cyst cavity did not show any significant change. Scleral buckling with external compression combined with external drainage of the intracystic fluid was performed, the patient's visual acuity was gradually restored to a normal 1.0 after the operation, and the retina appeared flattened. The patient was finally diagnosed with a giant retinal cyst with retinoschisis in the right eye. The presumed cause was heavy coughing leading to rupture and hemorrhage of the retinal cyst, similar to the mechanism of rupture of an arterial dissection. To the best of our knowledge, this case of retinal cyst rupture and hemorrhage caused by heavy coughing with good recovery after external surgical treatment has never been reported before. CONCLUSIONS: Giant cystic retinal hemorrhage with retinoschisis is very rare. Orbital magnetic resonance imaging and ocular B-scan ultrasound are essential for its diagnosis, and the selection of an appropriate surgical procedure is necessary to maximize the benefit for affected patients.

Isolation of Tulasnella spp. from Cultivated Paphiopedilum Orchids and Screening of Germination-Enhancing Fungi.

Ex situ conservation, an important way to increase the survival and sustainability of endangered species, is widely used in the conservation of endangered orchids. However, long-term ex situ conservation might affect the dominant group of orchid symbiotic fungi, which are crucial for orchid growth and reintroduction. This study investigated the culturable Tulasnella spp. associated with Paphiopedilum orchids after long-term greenhouse cultivation, and identified germination-enhancing isolates. A total of 44 Tulasnella isolates were obtained from the roots of 14 Paphiopedilum spp., and 29 of them were selected for phylogenetic analysis. They clustered mainly with Tulasnella deliquescens, Tulasnella calospora, Tulasnella bifrons, and Tulasnella irregularis, but included two potential new groups. Compared with published uncultured data, most of the isolates were grouped together with the reported types, and the dominant Tulasnella associated with P. armeniacum and P. micranthum could still be isolated after ten years of cultivation, most of which were the first isolation. In vitro symbiotic germination showed that certain root isolates could promote seed germination (e.g., parm152 isolated from P. armeniacum, Php12 from P. hirsutissimum, and prhi68 from P. rhizomatosum). These data indicated that the dominant Tulasnella types colonizing the roots of cultivated Paphiopedilum are stable over time, and germination-enhancing fungi colonizing the roots would benefit for seed reproduction after population reintroduction into the wild.

The Function of Spag6 to Repair Brain Edema Damage After Cerebral Ischemic Stroke-reperfusion.

Sperm associated antigen 6 (Spag6) is the PF16 homolog of Chlamydomonas and participates in the regulation of cilia movement. Studies have shown that Spag6 is expressed in the brain, and its loss will lead to cerebral edema caused by a defect in motor cilium function in ependymal cells. However, it has not been reported whether the limited or extensive cerebral edema resulting from ischemic strokes is related to the expression regulation of Spag6. Therefore, this study aimed to investigate the effect and related mechanism of Spag6 in alleviating Cerebral Ischemic stroke-reperfusion (CIS/R) damage. Our experimental results showed that Spag6 overexpression alleviated CIS/R-mediated motor cilia structural disorder, improved cerebral edema, inhibited nerve injuries in rats with cerebral ischemia, and alleviated synaptic and dendritic spinal injuries by regulating the expressions of synaptic-related proteins such as CaMKII, PSD95, and CREB. Based on significant changes in PI3K/AKT-mTOR signaling pathway activity after CIS/R determination, we determined that Spag6 regulates the abnormal expression of CIS/R-induced inflammatory factors NF-κB, NLRP3, IL-10, and the autophagy-related proteins Beclin-1, LC3, and P62 by activating the PI3K/AKT-mTOR signaling pathway. This inhibits inflammation and autophagy in the brain tissue. In summary, this study revealed that Spag6 alleviates brain edema damage after CIS/R by maintaining the structural function of the motor cilium, regulating the PI3K/AKT-mTOR signaling pathway, and inhibiting inflammation and autophagy reaction.

The correlation between non-arteritic anterior ischemic optic neuropathy and cerebral infarction.

Background: The aim of this study was to explore the correlation between non-arteritic anterior ischemic optic neuropathy (NAION) and cerebral infarction (CI). Moreover, the ocular and systemic parameters are also compared between NAION patients with or without CI. Methods: Retrospective analysis is performed for NAION patients and the controls. The controls were collected at the eye outpatient with cranial computed tomography (CT), and data of blood triglyceride, cholesterol, low-density lipoprotein, high-density lipoprotein, and apolipoprotein B were drawn. The diagnosed NAION patients with cranial CT are included, and data of clinical history and routine clinical examination were drawn from the medical record. Visual acuity, intraocular pressure (IOP), visual field, and visual evoked potential were also drawn. Results: Eighty-two unilateral and 6 bilateral patients, totally 94 eyes for 88 NAION patients and 69 controls are included. NAION and control patients have matched age, gender, and weight. There is no difference in triglyceride, cholesterol, low-density lipoprotein, high-density lipoprotein, and apolipoprotein B between these two groups. NAION patients (43.18%, 38/88) have a higher ratio of CI than the controls (14.49%, 10/69) (p = 0.000). For NAION, the odds ratio (OR) of CI is 2.691 (p = 0.011). Body mass index, height, and IOP show no significant difference between NAION patients with or without CI. NAION patients with CI have a significant higher ratio of hypertension than those without CI, and the OR of HBP is 2.623 (p = 0.008). Conclusions: The correlation between NAION and CI is possible as NAION patients have a significant higher ratio with CI. In NAION patients, hypertension is a risk factor for those with CI.

Pharmacy student's perceptions, behaviours and attitudes toward virtual reality simulation.

Aims: The definition of virtual reality simulation (VRS) used for study is the recreation of realistic simulation in a fully online situation with an immersive environment for learning an activity. The study aims to evaluate pharmacy students' perspectives, behavioral and attitude characteristics in the process of VRS course requiring practical skills. Materials and methods: This cross-sectional study was based on quantitative questionnaires analysis. A five-point Likert Scale (rating from 1 = Strongly Disagree; 2 = Disagree; 3 = Neutral; 4 = Agree; 5 = Strongly Agree) was utilized to measure the extent to which the students agrees on 30 statements comprised in A-E sections related to VRS. The validity and reliability of the questionnaire were studied by the Cronbach's Alpha calculation. Results: A total of 119 junior and senior pharmacy students, aged 18-25, participated in this study. There is no significant gender difference (P > 0.05) and grade difference (P > 0.05) in mean perception score, mean attitude score, mean behavior score and comparison score respectively. Most pharmacy students had positive perception that VRS could help them in practical ability (61.4 %), autonomous learning (68.9 %) and theoretical knowledge (61.4 %). Nevertheless, less than half the students agreed that VRS courses were indispensable (44.5 %) and needed to be increased (42.9 %). Moreover, the 'disagree' statement (33.6 %) exceeded 'agree' statement (27.7 %) about the question of whether preferring VRS courses to lab teaching. Interestingly, a significant positive correlation that was observed between mean perception score and mean attitude score (r = 0.76, p < 0.001), mean comparison (r = 0.68, p < 0.001) and mean behavior (r = 067, p < 0.001), which revealed that students who thought VRS was beneficial were more likely to accept it. Conclusion: The study highlights the need to establish an interactive, immersive and measurable VRS courses. It is suggested that good interaction between the faculty and student, technology improvement and blended programmatic assessment should be involved in challenges for implementing VRS courses.

MRTF-A alleviates myocardial ischemia reperfusion injury by inhibiting the inflammatory response and inducing autophagy.

Myocardin-related transcription factor A (MRTF-A) has an inhibitory effect on myocardial infarction; however, the mechanism is not clear. This study reveals the mechanism by which MRTF-A regulates autophagy to alleviate myocardial infarct-mediated inflammation, and the effect of silent information regulator 1 (SIRT1) on the myocardial protective effect of MRTF-A was also verified. MRTF-A significantly decreased cardiac damage induced by myocardial ischemia. In addition, MRTF-A decreased NLRP3 inflammasome activity, and significantly increased the expression of autophagy protein in myocardial ischemia tissue. Lipopolysaccharide (LPS) and 3-methyladenine (3-MA) eliminated the protective effects of MRTF-A. Furthermore, simultaneous overexpression of MRTF-A and SIRT1 effectively reduced the injury caused by myocardial ischemia; this was associated with downregulation of inflammatory factor proteins and when upregulation of autophagy-related proteins. Inhibition of SIRT1 activity partially suppressed these MRTF-A-induced cardioprotective effects. SIRT1 has a synergistic effect with MRTF-A to inhibit myocardial ischemia injury through reducing the inflammation response and inducing autophagy.

Epidendrumradicans Fungal Community during Ex Situ Germination and Isolation of Germination-Enhancing Fungi.

Orchids exhibit varying specificities to fungi in different microbial environments. This pilot study investigated the preference of fungal recruitment during symbiotic germination of Epidendrum radicans Pav. ex Lindl. Two different orchid substrates were used for ex situ seed baiting: pine bark and rotten oak leaf, with Basidiomycota and Ascomycota as the respective dominant groups. Both substrates promoted seed germination, with a higher protocorm formation rate on pine bark (65.75%). High-throughput sequencing characterized the fungal communities of germinated protocorms. Basidiomycota was the dominant group in protocorms that symbiotically germinated on both substrates. The family-level community structures of endophytic fungi in protocorms that symbiotically germinated on both substrates were close to those of protocorms that germinated in vitro on MS1 medium. For protocorms, the dominant fungal groups recruited from substrates differed at the genus level; from pine bark, they were genera belonging to unclassified Sebacinales (41.34%), Thanatephorus (14.48%) and Fusarium (7.35%), while, from rotten oak leaf, they were Rhizoctonia (49.46%), Clitopilus (34.61%), and Oliveonia (7.96%). Four fungal isolates were successfully obtained and identified as belonging to the family Tulasnellaceae, genera Ceratobasidium and Peniophora, which could promote seed germination to the seedling stage. The data indicate that endophytic fungi for E. radicans germination on two different substrates are affected at the genus level by the substrate, with a degree of specificity at the family level.

Long anterior lens zonules with retinal stripes: a case report.

BACKGROUND: Long anterior lens zonules (LAZs) is a rare disease that was mostly conducted among African Americans. Through the observation of a Chinese patient, we discoverd that the disease may show different characteristics in Asians. CASE PRESENTATION: A patient with vision loss due to a macular hole was found to have several special clinical signs during vitrectomy combined with phacoemulsification and intraocular lens implantation surgery in our hospital, including radially oriented lines on the anterior capsule with pigment, a shallow anterior chamber, slightly high intraocular pressure, and radial retinal stripes in the peripheral retina. Finally, he was diagnosed with long anterior lens zonule syndrome. CONCLUSION: Clinicians need to pay more attention to the rare disease LAZs. It is important to tear the appropriate size of the anterior capsule so as to avoid radial capsular tearing and intraocular lens dislocation.

Biomechanical evaluation of percutaneous anterograde and retrograde screw implantation for superior ramus pubis fractures: a finite element analysis.

OBJECTIVE: To evaluate the biomechanical characteristics of percutaneous anterograde and retrograde screw implantation for superior ramus pubis fractures. METHODS: Mimics software was used to reconstruct the normal pelvis. 3-Matic software was used to establish a model for superior ramus pubis fracture, and percutaneous anterograde/retrograde screw implantation was used to simulate the treatment of a superior ramus pubis fracture. After material assignment by Mimics software, Ansys software simulated the force of a standing position with a 600 N load on an S1 vertebral endplate and then compared the mechanical stability. RESULTS: After simulating the fracture at five points, the effect of anterograde and retrograde screw implantation on the displacement and stress of the pelvis and the left pubic bone were found to be similar. When anterograde screw implantation was used, screw displacement at each point was 1.10 mm, 1.04 mm, 1.10 mm, 1.10 mm, and 1.07 mm; the stress at each point was 14.95 MPa, 11.50 MPa, 18.60 MPa, 18.07 MPa, and 18.37 MPa. When retrograde screw implantation was used, screw displacement at each point was 0.62 mm, 0.62 mm, 0.70 mm, 0.76 mm, and 0.87 mm; and the stress at each point was 5.13 MPa, 4.03 MPa, 6.61 MPa, 9.74 MPa, and 11.55 MPa respectively. CONCLUSIONS: When assessing the treatment of superior ramus pubis fractures from a biomechanical perspective, we found that if the distance between the fracture line and the insertion point is less than 70 mm, it is recommended to use retrograde screw implantation.

Effects of Rare Earth Elements on Blood Pressure and Their Exposure Biomarkers: Evidence from Animal Experiments.

Solid fuel combustion is an important source of the release of rare earth elements (REEs) into the ambient environment, resulting in potential adverse effects on human cardiovascular health. Our study aimed to identify reliable exposure biomarkers of REE intake and their potential role in blood pressure change. A total of 24 rats were administered with 14 REE chlorides at four doses (six rats per group). Fur samples were collected both before and after administration. Blood samples were collected after 12 weeks of REE intake. The REE concentrations in rat fur and blood samples were measured by inductively coupled plasma mass spectrometry. For each week, blood pressure, as well as heart rate and pulse pressure, were measured. The linear mixed-effect model was used to analyze the relationship between REE administration dose and blood pressure change. We found that the REE concentration in fur, but not blood, samples exhibited significant dose-response relationships with administration dose. It suggested that hair samples are a more efficient matrix for indicating the exposure level of a population to REEs than blood samples. However, there was no dose-response relationships between the administration dose and blood pressure change of rats, or with heart rate and pulse pressure for the 14 REEs. We also did not find a dose-response relationship between REE administration levels and plasma concentration of 8-hydroxy-2'-deoxyguanosine, as an important DNA oxidative stress damage biomarker. In conclusion, hair samples are more suitable as a sample type to reliably assess exposure to REEs than blood samples, and REEs did not have a direct adverse effect on blood pressure in our rat model.

Baicalin Inhibits NLRP3 Inflammasome Activity Via the AMPK Signaling Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury.

Baicalin has been reported to have ameliorative effects on nerve-induced hypoxic ischemia injury; however, its role in the NLRP3 inflammasome-dependent inflammatory response during cerebral ischemia-reperfusion remains unclear. To investigate the molecular mechanisms involved in baicalin alleviating cerebral ischemia-reperfusion injury, we investigated the AMPK signaling pathway which regulates NLRP3 inflammasome activity. SD rats were treated with baicalin at doses of 100 mg/kg and 200 mg/kg, respectively, after middle cerebral artery occlusion at 2 h and reperfusion for 24 h (MCAO/R). MCAO/R treatment significantly increased cerebral infarct volume, changed the ultrastructure of nerve cells, and activated the NLRP3 inflammasome, manifesting as significantly increased expression of NLRP3, ASC, cleaved caspase-1, IL-1ß, and IL-18. Our results demonstrated that baicalin treatment effectively reversed these phenomena in a dose-dependent manner. Additionally, inhibition of NLRP3 expression was found to promote the neuroprotective effects of baicalin on cortical neurons. Furthermore, baicalin remarkably increased the expression of p-AMPK following oxygen glucose deprivation/reperfusion (OGD/R). The expression of the NLRP3 inflammasome was also increased when the AMPK pathway was blocked by compound C. Taken together, our findings reveal that baicalin reduces the activity of the NLRP3 inflammasome and consequently inhibits cerebral ischemia-reperfusion injury through activation of the AMPK signaling pathway.

In silico-determined compound from the root of Pueraria lobate alleviates synaptic plasticity injury induced by Alzheimer's disease via the p38MAPK-CREB signaling pathway.

Pueraria lobata is utilized as a food source in China. The aim of this study is to combine virtual screening and molecular dynamics predictive model to screen out the potential synaptic plasticity-maintaining components from the root of P. lobate and to verify it by employing the amyloid ß-injected rats' model. Eighteen compounds were identified by HPLC-MS/MS; puerarin manifested the most potential to form a stable complex with calcium/calmodulin kinase IIα (CaMK IIα), which is the key protein in synaptic plasticity by the in silico study. The further in vivo assay showed that puerarin could elevate the synaptic thickness, density, and length, relieve calcium overload, regulate the expression of CaMK IIα, and other p38MAPK-CREB signaling pathway-related biochemical criteria. The behavioral test also verified the results. Results have confirmed that the root of P. lobate can work anti-AD by maintaining the synaptic plasticity and proved the reliability of using the in silico predictive model to determine active ingredients from the natural product.

Selection of suitable reference genes for quantitative real time PCR in different Tulasnella isolates and orchid-fungus symbiotic germination system.

Under natural conditions, mycorrhizal symbiosis accompanies nearly the entire life cycle of orchids from seed germination through to flowering and fruiting. Tulasnella-like orchid mycorrhizal fungi are the most common mycorrhizal fungi found in association with orchid species. Presently suitable reference genes have not been systematically selected for the quantification of gene expression via Real-Time Quantitative Reverse Transcription PCR (RT-qPCR). We evaluated 12 candidate Tulasnella genes in nine different Tulasnella isolates and in the Dendrobium-fungal symbiotic germination associations followed by statistical analysis using the programs Bestkeeper, geNorm, and Normfinder to analyze the expression stability of the individual genes. The results showed that the EF2, UBC, and PP2A genes had the highest rankings with relatively stable expression levels across the different genotypes and during the symbiotic seed germination process by the three programs, and may be suitable for RT-qPCR normalization. Furthermore, the gene encoding C-5 Sterol desaturase (C5SD) was selected to verify the reliability of EF2, UBC, and PP2A expression during the Tulasnella-Dendrobium symbiotic seed germination process. This study is the first systematic exploration of optimal reference genes for gene expression studies during the colonization of orchid seeds by the mycorrhizal fungus Tulasnella.

The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats.

BACKGROUND: Acrylamide (ACR) formed during heating of tobacco and carbohydrate-rich food as well as widely applied in industries has been known as a well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats. METHODS: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40 mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the cerebral homogenates were detected using ELISA assay. RESULTS: ACR-induced weigh loss, deficits in motor function as well as pathological alterations in brains were significantly improved in rats administrated with 50 and 100 mg/kg curcumin. TUNEL-positive apoptotic cells in curcumin-treated ACR intoxicated brains were less than those in the ACR model group. Curcumin administration especially at the dose of 100 mg/kg upregulated the TERT mRNA expression and enhanced the number of TERT-positive cells in ACR-intoxicated cortex tissues. Moreover, curcumin treatment reduced the concentrations of TNF-α, IL-1ß and MDA, while increased the GSH contents as well as the SOD and GSH-Px activities in the cerebral homogenates, in comparison to ACR control group. CONCLUSIONS: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. Maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

[Clinical path of mechanical ventilation and atomization inhalation therapy].

In recent years, atomization inhalation therapy has been more and more commonly used in patients with mechanical ventilation. However, the establishment of artificial airway has changed the environment and mode of aerosol delivery. Currently, Expert consensus on atomization inhalation during mechanical ventilation has been established to guide clinical practice. However, many ventilators do not support the treatment of aerosol inhalation due to the tedious procedures and numerous drugs. At the same time, the therapeutic effect of atomization inhalation is affected by many factors, such as ventilator mode selection, parameter setting, heating and humidification, using of artificial nose and filter, etc., which often results in poor clinical effects or even damage to the ventilator. In order to standardize the clinical application of mechanical ventilation atomization inhalation technology and avoid many possible problems in operation, the committee members of Respiratory Therapy Group of Severe Medicine Branch of Henan Medical Association discussed and concluded this clinical path, so as to provide clinical reference for the actual operation and drug administration of mechanical ventilation atomization.

The in silico and in vivo evaluation of puerarin against Alzheimer's disease.

The root of Pueraria lobata has been utilized as a food source for thousands of years in China. Puerarin is the major bioactive and the most abundant secondary metabolite obtained from the root of P. lobata. The potential therapeutic effect of puerarin against Alzheimer's disease was screened by in silico methods and confirmed by the amyloid ß-peptide-induced Alzheimer's disease (AD) rat model. The in silico study displayed that puerarin had the potential to penetrate across the blood-brain barrier and had high stability in molecular docking and dynamics simulation with acetylcholinesterase (AChE), cyclooxygenase-2 (COX-2) and caspase-3 (C3), which play a central role in the development of AD. The in vivo results showed that puerarin could restrain the AChE activity, restore the activities of antioxidant defense substances toward normal levels, and decrease the expression of inflammatory factors and apoptosis genes in the brain, especially down-regulating the expressions of COX-2 and C3. The histopathological examination of brain sections and behavioral testing also verified the biochemical observations, which further validates the in silico study. These results not only suggest that puerarin, as a potential compound, could relieve AD, but also broaden the applications of puerarin.

Anti-inflammatory effect of external use of escin on cutaneous inflammation: possible involvement of glucocorticoids receptor.

Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor (GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (P38MAPK) and activator protein-1 (AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1ß. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.

Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats.

Our recent study has revealed that the myocardin-related transcription factor-A (MRTF-A) is involved in the apoptosis of cortical neurons induced by ischemia/reperfusion (I/R). Histone deacetylase 5 (HDAC5) and histone acetyltransferase p300 (P300) are two well-known regulators for transcription factors; however, their roles in MRTF-A-related effect on neuronal injuries during I/R are still unclear. In this study, in a model rat cerebral I/R injury via middle cerebral artery occlusion and reperfusion, we found that the expression and activity of HDAC5 was upregulated, whereas p300 and MRTF-A were downregulated both in expression and activity during I/R. Their expression changes and the interaction of the MRTF-A with HDAC5 or p300 were further verified by double immunofluorescence and co-immunoprecipitation. In cultured neuronal apoptosis model induced by H2O2, MRTF-A exhibited an anti-apoptotic effect by enhancing the transcription of Bcl-2 and Mcl-1 via CArG box binding. MRTF-A-induced anti-apoptotic effect was effectively inhibited by HDAC5, but was significantly enhanced by p300. The results suggest that both HDAC5 and p300 are involved in MRTF-A-mediated effect on neuronal apoptosis during ischemia/reperfusion injury, but with opposite effects.

The role of myocardin-related transcription factor-A in Aß25-35 induced neuron apoptosis and synapse injury.

Myocardin-related transcription factor-A (MRTF-A) highly expressed in brain has been demonstrated to promote neuronal survival via regulating the transcription of related target genes as a powerful co-activator of serum response factor (SRF). However, the role of MRTF-A in Alzheimer's disease (AD) is still unclear. Here, we showed that MRTF-A was significantly downregulated in cortex of the Aß25-35-induced AD rats, which played a key role in Aß25-35 induced cerebral neuronal degeneration in vitro. Bilateral intracerebroventricular injection of Aß25-35 caused significantly MRTF-A expression decline in cortex of rats, along with significant neuron apoptosis and plasticity damage. In vitro, transfection of MRTF-A into primary cultured cortical neurons prevented Aß25-35 induced neuronal apoptosis and synapses injury. And luciferase reporter assay determined that MRTF-A could bind to and enhance the transactivity of the Mcl-1 (Myeloid cell leukemia-1) and Arc (activity-regulated cytoskeletal-associated protein) promoters by activating the key CArG box element. These data demonstrated that the decreasing of endogenous MRTF-A expression might contribute to the development of AD, whereas the upregulation MRTF-A in neurons could effectively reduce Aß25-35 induced synapse injury and cell apoptosis. And the underlying mechanism might be partially due to MRTF-A-mediated the transcription and expression of Mcl-1 and Arc by triggering the CArG box.

Protective effect of n-butyl alcohol extracts from Rhizoma Pinelliae Pedatisectae against cerebral ischemia-reperfusion injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Pinelliae Pedatisectae (RPP) has been commonly used in traditional Chinese medicine (TCM) for treatment of various neurological related diseases. However, the mechanisms have not been fully clarified yet. The present study was designed to investigate the therapeutic effect of RPP against cerebral ischemic/reperfusion (I/R) injury in rats models, and more importantly, to explore the underlying mechanism. MATERIALS AND METHODS: Cerebral ischemia and reperfusion was established through the classic middle cerebral artery occlusion (MCAO) for 2h, followed by 24h reperfusion. Rats were orally given different doses of n-butyl alcohol extracts (NBES) of RPP or saline for one week before induction of ischemia. Neurological defect scoring, cerebral infarct volume, oxidative stress markers, inflammatory reaction and nerve cell apoptosis were then estimated. RESULTS: It showed that NBES could alleviate in a dose-dependent manner neurological deficit and reduce the infarct volume in vivo. The protective effects of NBES were associated with increased Superoxide dismutase (SOD) activity and decreased malonaldehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels. In addition, ischemia-induced neuron apoptosis was inhibited by NBES pretreatment, and western blot showed NBES upregulated expressions of B-cell leukemia-2 (Bcl-2) and downregulated Bcl-2-associated X (Bax) expression. CONCLUSION: NBES prevent cerebral I/R injury by alleviating neuronal oxidative injury, inflammatory reaction and neuron apoptosis. The research for the traditional use of RPP provided certain theoretical basis.