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BACKGROUND: The neuroendoscopic approach has the advantages of a clear operative field, convenient tumor removal, and less damage, and is the development direction of modern neurosurgery. At present, transnasal surgery for sphenoidal pituitary tumor is widely used. But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts. AIM: To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors. METHODS: A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups, with 30 in each group. Experimental group: After anesthesia, a gastric tube was placed through the mouth under direct vision using a visual laryngoscope, and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection, during the operation, and when the patient recovered from anesthesia. Control group: Given the routine intraoperative care, no gastric tube was left. The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups; the scores of pharyngalgia after waking up, 6 h post-operation, and 24 h post-operation. The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared. The hospitalization days of the two groups were statistically compared. RESULTS: The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group, and the difference in the incidence of nausea was statistically significant (P < 0.05). After the patient woke up, the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group, and the difference was statistically significant (P < 0.05). The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group, but there was no statistically significant difference from the control group (P > 0.05). The hospitalization days of the experimental group was lower than that of the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors, combined with intraoperative and postoperative gastrointestinal decompression, can effectively reduce the incidence of nausea, reduce the number of vomiting and aspiration in patients, and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.
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OBJECTIVE: To investigate the value of 99mTc-pertechnetate scan in postoperative differentiated thyroid cancer (DTC) patients with lymph node (LN) metastases (LNM) uptake 99mTc-pertechnetate, especially the predictive value to their response to radioiodine-131 (131I) therapy. METHODS: This retrospective study collected 752 patients with DTC and LNM treated at Zhejiang Cancer Hospital between May 2012 and December 2017. Depending on the ability of LNM uptake 99mTc-pertechnetate, the patients were grouped as the 99mTc-pertechnetate-avid (n=88) vs. 99mTc-pertechnetate-non-avid (n=664) groups. And Propensity score matching (PSM) was performed at a 1:4 ratio to reduce confounding bias. RESULTS: In the PSM analysis, the 1:4 matched cohort comprised 752 patients (88 with 99mTc-pertechnetate-avid LNM, 664 with 99mTc-pertechnetate-non-avid LNM). Patients' age, initial 131I activity and frequency of iodine therapy were included as covariates. After PSM analysis, 363 patients (99mTc-pertechnetate-avid group, n=83; 99mTc-pertechnetate-non-avid group, n=280) were successfully matched. Among the 363 PSM-matched patients, 48/83 (57.8%) in the 99mTc-pertechnetate-avid group and 158/280 (56.4%) in the 99mTc-pertechnetate-non-avid group had two or more 131I treatments. The nsTg and the percentage of changes in ssTg between the 99mTc-pertechnetate-avid and 99mTc-pertechnetate-non-avid groups were significantly different ([0.05 (0.04 to 0.90) vs. 0.40 (0.04 to 4.92), p=0.018] and [-88% (-98%, -50%) vs. -66% (-86%, -30%), p < 0.001], respectively). No significant differences were observed between the two groups in the other parameters (age, pathological type, distant metastasis, follow-up time, AJCC TNM stage, initial 131I treatment activity, and 131I treatment frequency) after PSM (all p > 0.05). CONCLUSION: In patients with DTC and LNM, LNM uptake of 99mTc-pertechnetate is a rare phenomenon. Patients with 99mTc-pertechnetate-avid LNMs were more likely to benefit from 131I therapy, even after adjustment for age, 131I treatment frequency, and initial 131I activity.
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Aluminum is a common environmental neurotoxin. Aluminum ions can cross the blood-brain barrier and accumulate in different brain regions, damage brain tissue, and cause cognitive impairment, but the molecular mechanism of aluminum neurotoxicity is not precise. This study investigated the effects of miR-204-5p, target gene EphB2, and downstream signaling pathway NMDAR-ERK-CREB-Arc on cognitive dysfunction induced by aluminum exposure. The results showed that the learning and memory of the rats were impaired in behavior. The accumulation of aluminum in the hippocampus resulted in the damage of nerve cell morphology in the CA1 region of the hippocampus. The expression level of miR-204-5p was increased, and the mRNA and protein expressions of EphB2, NMDAR2B, ERK1/2, CREB, and Arc were decreased. The results indicated that the mechanism of impaired learning and memory induced by aluminum exposure might promote the expression of miR-204-5P and further inhibit the expression of the target gene EphB2 and its downstream signaling pathway NMDAR-ERK-CREB-Arc.
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Objective: Brainstem hematoma (BSH) is a high-risk condition that can lead to deadly and disabling consequences if not properly managed. However, recent advances in endoscopic techniques, employed for removing supratentorial intracerebral hemorrhage have shown significant improvements in operative morbidity and mortality rates compared to other approaches. In this study, we demonstrate the utility and feasibility of the endoscopic trans-cerebellar medullary fissure approach for the management of brain stem hemorrhage in carefully selected patients. Patients and methods: A 55-year-old man presented to the emergency department in a comatose state with respiratory distress. A CT scan revealed the presence of a brainstem hemorrhage. Given the location of the hemorrhage and the need to quickly manage the associated developmental obstructive hydrocephalus and respiratory distress, an endoscopic trans-cerebellar medullary fissure approach was chosen as the most appropriate method of treatment. Results: Total resection was achieved, and the patient gradually improved postoperatively with no new neurological deficits. He is currently under routine follow-up and is conscious but has partial hemiplegia. Conclusion: This approach provided direct visualization of the lesion and was minimally invasive. The endoscopic trans-cerebellar medullary fissure approach may be considered an alternative to open approaches for brainstem hemorrhage in carefully selected patients.
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BACKGROUND: Neuroendoscopy is a very useful technique to Chronic Subdural Hematoma (CSH). But how to achieve the goal of treatment more minimally invasive? AIM: To develop a simple, fast and accurate preoperative planning method in our way for endoscopic surgery of patients with CSH. METHODS: From June 2018 to May 2020, forty-two patients with CSH, admitted to our hospital, were performed endoscopic minimally invasive surgery; computed tomography (CT) imaging was employed to locate the intracerebral hematoma and select the appropriate endoscopic approach before the endoscopic surgery. The clinical data and treatment efficacy were analyzed. RESULTS: According to the learning of CT scanning images, the surgeon can accurately design the best minimally invasive neuroendoscopic surgical approach and realize the precise positioning and design of the drilling site of the skull and the size of the bone window, so as to provide the most effective operation space with the smallest bone window. In this group, the average operation time was only about 1 h, and the clearance rate of hematoma was about 95%. CONCLUSION: Patients with CSH can achieve good therapeutic effect by using our way to positioning and design to assist the operation of CSH according to CT scan and image, and our way is very useful and necessary.
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Data redundancy and data loss are relevant issues in condition monitoring. Sampling strategies for segment intervals can address these at the source, but do not receive the attention they deserve. Currently, the sampling methods in relevant research lack sufficient adaptability to the condition. In this paper, an adaptive sampling framework of segment intervals is proposed, based on the summary and improvement of existing problems. The framework is implemented to monitor mechanical degradation, and experiments are implemented on simulation data and real datasets. Subsequently, the distributions of the samples collected by different sampling strategies are visually presented through a color map, and five metrics are designed to assess the sampling results. The intuitive and numerical results show the superiority of the proposed method in comparison to existing methods, and the results are closely related to data status and degradation indicators. The smaller the data fluctuation and the more stable the degradation trend, the better the result. Furthermore, the results of the objective physical indicators are obviously better than those of the feature indicators. By addressing existing problems, the proposed framework opens up a new idea of predictive sampling, which significantly improves the degradation monitoring.
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Simulación por ComputadorRESUMEN
Objective @#To examine the association between dietary patterns during pregnancy and gestational diabetes mellitus (GDM), so as to provide the evidence for guiding the establishment of healthy and balanced dietary patterns and reducing the prevalence of GDM.@*Methods@#Pregnant women who underwent oral glucose tolerance tests in Hangzhou Obstetrics and Gynecological Hospital from 2020 to 2021 were enrolled, and their demographic information were collected using questionnaires. Pregnant women's diets during the past three months were collected using Food Frequency Questionnaires (FFQs), and dietary patterns were extracted using principal component analysis. In addition, the association between dietary patterns and risk of GDM was examined using a multivariable logistic regression model.@*Results@# A total of 1 689 pregnant women were included, with a median age of 28.53 (interquartile range, 2.47) years and a median gestational age of 26.00 (interquartile range, 2.00) weeks. Five dietary patterns were identified according to pregnant women's types of diets, including meat-based diets, dessert-fruit-refined grain diets, plant-based diets, eggs-milk-nut diets and whole-grain diets, with a cumulative contribution rate of 58.76%. The prevalence of GDM was 24.57% (415 cases) among the study subjects. Multivariable logistic regression analysis showed that pregnant women with scores in the highest quartile (Q4) of the meat-based diets had an increased risk of GDM (OR=1.372, 95%CI: 1.043-2.055) relative to those with scores in the lowest quartile (Q1), and pregnant women with Q4 scores of the dessert-fruit-refined grain diets had an increased risk of GDM (OR=1.743, 95%CI: 1.397-2.432) relative to those with Q1 scores, while pregnant women with Q4 scores of the plant-based diets had a reduced risk of GDM (OR=0.382, 95%CI: 0.346-0.613) relative to those with Q1 scores.@*Conclusion@#A plant-based dietary pattern may reduce the risk of GDM, while meat-based and dessert-fruit-refined grain dietary patterns may increase the risk of GDM.
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BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease in neurosurgery. The traditional treatment methods include burr hole drainage, bone flap craniectomy and other surgical methods, and there are certain complications such as recurrence, pneumocephalus, infection and so on. With the promotion of neuroendoscopic technology, its treatment effect and advantages need to be further evaluated. AIM: To study the clinical effect of endoscopic small-bone approach in CSDH. METHODS: A total of 122 patients with CSDH admitted to our hospital from August 2018 to August 2021 were randomly divided into two groups using the digital table method: the neuroendoscopy group (n = 61 cases) and the burr hole drainage group (n = 61 cases). The clinical treatment effect of the two groups of patients with CSDH was compared. RESULTS: At the early postoperative stage (1 d and 3 d), the proportion of 1/2 re-expansion of brain tissue in the hematoma cavity and the proportion of complete re-expansion was higher in the neuroendoscopy group than in the burr hole drainage group, and the difference between the two groups was statistically significant (P < 0.05). The recurrence rate of hematoma in the neuroendoscopy group was lower than that in the burr hole drainage group, and the difference between the two groups was statistically significant (P < 0.05). No intracranial hematoma, low cranial pressure, tension pneumocephalus or other complications occurred in the neuroendoscopy group. CONCLUSION: The neuroendoscopic approach for the treatment of CSDH can clear the hematoma under direct vision and separate the mucosal lace-up. The surgical effect is apparent with few complications and definite curative effect, which is worthy of clinical promotion and application.
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The phase behavior of ABC star terpolymers confined between two identical parallel surfaces is systematically studied using a simulated annealing method. Several phase diagrams are constructed for systems with different bulk phases or with different interfacial interaction strength ratios in the space of surface distance (D) and surface preference for different arms, or in the space of D and the arm-length ratio x. Phases, including tiling patterns [6.6.6], [8.8.4], [8.6.6; 8.6.4], [8.6.6; 8.6.4; 10.6.6; 10.6.4] and hierarchical lamellar structures of lamella + cylinders and lamella + rods, are identified both in the bulk and in the films. Our results suggest that the self-assembled structure of a phase is largely controlled by x, while an increase of the interfacial interaction strength ratio shifts the x-window for each phase to the smaller x side. The orientation of a confined phase depends on the "effective surface preference" which is a combined effect of the interfacial interaction strength ratio, the surface preference, and the entropic preference. In the case of neutral or weak "effective surface preference", phases with a perpendicular orientation are usually observed, while in the case of strong "effective surface preference" phases with a perpendicular orientation or also with outermost wetting-layers can be frequently observed under some circumstances.
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Achiral block copolymers can self-assemble into helical structures when confined inside a cylindrical nanopore. However, controlling the chirality and the number of strands of helices is challenging. We present our simulation results of the influence of a chiral patch added to the confining nanopore on the structures and chirality of helices self-assembled from achiral cylinder-forming diblock copolymers under the confinement. Our results indicate that, when the designed patch is of proper geometry, it can induce the formation of helical structures and exhibit good control over their chirality. The bottom surface of the patch can induce the formation of a characteristic local structure near and parallel to it. It is the characteristic local structure that directs the formation of helices and of their chirality consistent with that of the patch. A large patch angle or the top/bottom surface of a weakly selective pore promotes the formation of double-helices compared to single-helices by enlarging the pitch of the helices near the patch or through the entropic attraction of the top surface of the pore to the minority blocks.
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Reactive oxygen species (ROS) exacerbate stroke-induced cell damage. We found that ShcA, a protein that regulates ROS, is highly expressed in a Rose Bengal photothrombosis model. We investigated whether ShcA is essential for mitophagy in ROS-induced cellular damage and determined whether ROS exacerbate mitochondrial dysfunction via ShcA protein expression. Ischemic stroke was generated by Rose Bengal photothrombosis in mice. To silence ShcA protein expression in the mouse brain, ShcA-targeting siRNA-encapsulated nanoparticles were intrathecally injected into the cisterna magna. Upon staining with antibodies against ShcA counterpart caspase-3 or NeuN, we found that the ShcA protein expression was increased in apoptotic neurons. In addition, mitochondrial dysfunction and excessive mitophagy were evident in photothrombotic stroke tissue. Infarct volumes were significantly reduced, and neurological deficits were diminished in the ShcA siRNA nanoparticle-treated group, compared with the negative control siRNA nanoparticle-treated group. We confirmed that the reduction of ShcA expression by nanoparticle treatment rescued the expression of genes, associated with mitochondrial dynamics and mitophagy mediation in a stroke model. This study suggests that the regulation of ShcA protein expression can be a therapeutic target for reducing brain damage with mitochondrial dysfunction caused by thrombotic infarction.
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Isquemia Encefálica , Accidente Cerebrovascular , Animales , Infarto Cerebral/etiología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de SrcRESUMEN
BACKGROUND: Prenatal stress increases the susceptibility of infants to seizures and is known to be associated with oxidative stress. Recent studies suggest that vitamin E has beneficial effects in various neurological diseases due to its antioxidant properties. In this study, we investigated the relationship between prenatal stress and vitamin E treatment on N-methyl-D-aspartate (NMDA)-induced spasms. METHODS: We used pregnant female Sprague Dawley rats and induced prenatal stress with an injection of betamethasone on G15. They were then treated orally with 200â¯mg/kg vitamin E or saline twice a day from G15-G21. On postnatal day 15, NMDA was administered to trigger spasms in offspring. The total number of spasms and latency to the first spasm were recorded. We also measured oxidative stress in the medial cortex using western blot, and calpain activity, thiobarbituric acid reactive substances (TBARS), glutathione (GSH)/GSH/glutathione disulfide (GSSG), superoxide dismutase (SOD) activity, catalase activity, and nitric oxide (NO) assays. RESULTS: We observed that rats treated with vitamin E while exposed to prenatal stress demonstrated reduced total number and frequency of spasms. Expression of glutamate decarboxylase 67 (GAD67) and K+/Cl- co-transporter (KCC2) were reduced after prenatal stress; this recovered in the vitamin E treated group. Further, expression of calpain 2 was decreased and various markers of oxidative stress (malondialdehyde (MDA), GSH/GSSG, SOD, catalase, and NO) were reduced in the vitamin E treated group. CONCLUSIONS: Our results provide evidence that vitamin E lowers oxidative stress and decreases seizure susceptibility in rat offspring exposed to prenatal stress. Given the well-known safety profile of vitamin E, these results indicate its potential as a strategy for preventing seizures.
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Calpaína , Vitamina E , Animales , Antioxidantes , Catalasa/metabolismo , Femenino , Glutatión/metabolismo , Estrés Oxidativo , Embarazo , Ratas , Ratas Sprague-Dawley , Espasmo , Superóxido Dismutasa/metabolismo , Vitamina E/uso terapéuticoRESUMEN
Because inflammation in osteoarthritis (OA) is related to the Toll-like receptor 4 (TLR4) signaling cascades, TLR4 is a reasonable target for developing therapeutics for OA. Thus, we investigated whether TAP2, a peptide antagonist of TLR4, reduces the monoiodoacetate (MIA)-induced arthritic pain and cartilage degradation in rats. TLR4 expression of human OA chondrocytes and synoviocytes and the knee joint tissue of MIA-induced arthritis were evaluated. MIA-induced arthritic model using Sprague-Dawley rats (6 week-old-male) were treated with TAP2, a TLR4 antagonist, and evaluated with behavioral test, immunohistochemistry, and quantitative PCR. TLR4 was highly expressed in the knee joints of patients with OA and the MIA-induced rat model. Further, a single intraarticular injection of TAP2 (25 nmol/rat) molecules targeting TLR4 on day 7 after MIA injection dramatically attenuated pain behavior for about 3 weeks and reduced cartilage loss in the knee joints and microglial activation in the spinal dorsal horns. Likewise, the mRNA levels of TNFα and IL-1ß, reactive oxygen species, and the expression of MMP13 in the knee joints of TAP2-treated rats was significantly decreased by TAP2 treatment compared with the control. Moreover, interestingly, the duration of OA pain relief by TAP2 was much longer than that of chemical TLR4 antagonists, such as C34 and M62812. In conclusion, TAP2 could effectively attenuate MIA-induced arthritis in rats by blocking TLR4 and its successive inflammatory cytokines and MMP13. Therefore, TAP2 could be a prospective therapeutic to treat patients with OA.
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Miembro 3 de la Subfamilia B de Transportadores de Casetes de Unión a ATP/química , Osteoartritis/tratamiento farmacológico , Dolor/tratamiento farmacológico , Receptor Toll-Like 4/antagonistas & inhibidores , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Cartílago Articular/citología , Células Cultivadas , Condrocitos/citología , Modelos Animales de Enfermedad , Humanos , Inflamación , Ácido Yodoacético , Masculino , Metaloproteinasa 13 de la Matriz/química , Inhibidores de la Metaloproteinasa de la Matriz/química , Osteoartritis/inducido químicamente , Manejo del Dolor , Péptidos/química , Ratas , Ratas Sprague-Dawley , Sinoviocitos/citologíaRESUMEN
The self-assembly of a cyclic AB copolymer system with relatively long A blocks and short B blocks in B-selective solvents is investigated using a simulated annealing method. By investigating the effect of the lengths and solubilities of A and B blocks (N A and N B, εAS and εBS), the incompatibility between A and B blocks (εAB), as well as the polymer concentration (C p) and the conditions for the formation of multicompartment vesicles in cyclic diblock copolymer solutions, is predicted. The phase diagrams in terms of N B, εAS, and C p are constructed. The mechanism of the morphological transition is elucidated. It is shown that for cyclic copolymers the change in the above factors relating to the polymer and solvent properties all can lead to the transition from simple vesicles to multicompartment vesicles, but two different transition mechanisms are revealed. In addition, our simulations demonstrate that the self-assembly of cyclic copolymers could provide a powerful strategy for regulating the compartment number and the wall thickness of the multicompartment vesicles by adjusting the block solubilities and block lengths, respectively. These findings will facilitate the application of multicompartment architectures in cell mimicry, drug delivery, and nanoreactors.
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Aims: We investigated whether miRNA (miR) 146a-5p-loaded nanoparticles (NPs) can attenuate neuropathic pain behaviors in the rat spinal nerve ligation-induced neuropathic pain model by inhibiting activation of the NF-κB and p38 MAPK pathways in spinal microglia. Materials & methods: After NP preparation, miR NPs were assessed for their physical characteristics and then injected intrathecally into the spinal cords of rat spinal nerve ligation rats to test their analgesic effects. Results: miR NPs reduced pain behaviors for 11 days by negatively regulating the inflammatory response in spinal microglia. Conclusion: The anti-inflammatory effects of miR 146a-5p along with nanoparticle-based materials make miR NPs promising tools for treating neuropathic pain.
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MicroARNs , Nanopartículas , Neuralgia , Animales , Glicolatos , Glicoles , Ácido Láctico , MicroARNs/genética , Microglía , Neuralgia/tratamiento farmacológico , Ratas , Ratas Sprague-DawleyRESUMEN
The effects of chain architecture and confinement on the structure and orientation of lamellae formed by incompressible and symmetric AB-type block copolymer melts confined between two parallel and identical surfaces are investigated using self-consistent field calculations on a simple cubic lattice. Five systems of various chain architectures (linear, ring, and star) and lengths are studied, with their bulk lamellar period L0 chosen such that they have comparable L0/Rg, where Rg denotes the ideal-chain radius of gyration. For thin films of thickness D = L0 confined between two neutral surfaces, we define the rescaled volume fraction profiles of A, B, chain end, and joint segments in the parallel and perpendicular lamellae such that these profiles can be directly compared among the five systems to quantitatively reveal the interplay between the chain-end enrichment near confining surfaces and the surface-induced A-B compatibilization, and how such interplay is affected by the chain architectures (for example, the chain-crowding effects in the star block copolymers). The effects of D and surface preference for one of the blocks are also investigated.
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BACKGROUND: Osteoarthritis (OA) is the most common type of joint disease associated with cartilage breakdown. However, the role played by mitochondrial dysfunction in OA remains inadequately understood. Therefore, we investigated the role played by p66shc during oxidative damage and mitochondrial dysfunction in OA and the effects of p66shc downregulation on OA progression. METHODS: Monosodium iodoacetate (MIA), which is commonly used to generate OA animal models, inhibits glycolysis and biosynthetic processes in chondrocytes, eventually causing cell death. To observe the effects of MIA and poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles, histological analysis, immunohistochemistry, micro-CT, mechanical paw withdrawal thresholds, quantitative PCR, and measurement of oxygen consumption rate and extracellular acidification rate were conducted. RESULTS: p-p66shc was highly expressed in cartilage from OA patients and rats with MIA-induced OA. MIA caused mitochondrial dysfunction and reactive oxygen species (ROS) production, and the inhibition of p66shc phosphorylation attenuated MIA-induced ROS production in human chondrocytes. Inhibition of p66shc by PLGA-based nanoparticles-delivered siRNA ameliorated pain behavior, cartilage damage, and inflammatory cytokine production in the knee joints of MIA-induced OA rats. CONCLUSION: p66shc is involved in cartilage degeneration in OA. By delivering p66shc-siRNA-loaded nanoparticles into the knee joints with OA, mitochondrial dysfunction-induced cartilage damage can be significantly decreased. Thus, p66shc siRNA PLGA nanoparticles may be a promising option for the treatment of OA.
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Mitocondrias/patología , Osteoartritis/tratamiento farmacológico , ARN Interferente Pequeño/farmacología , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/genética , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/metabolismo , Animales , Cartílago Articular/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Ácido Yodoacético/toxicidad , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/efectos de los fármacos , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Mitocondrias/metabolismo , Nanopartículas/administración & dosificación , Nanopartículas/química , Nanopartículas/uso terapéutico , Osteoartritis/inducido químicamente , Osteoartritis/patología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , ARN Interferente Pequeño/administración & dosificación , Ratas Sprague-DawleyRESUMEN
Osteoarthritis (OA) is the most common joint disorder that has had an increasing prevalence due to the aging of the population. Recent studies have concluded that OA progression is related to oxidative stress and reactive oxygen species (ROS). ROS are produced at low levels in articular chondrocytes, mainly by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and ROS production and oxidative stress have been found to be elevated in patients with OA. The cartilage of OA-affected rat exhibits a significant induction of p47phox, a cytosolic subunit of the NADPH oxidase, similarly to human osteoarthritis cartilage. Therefore, this study tested whether siRNA p47phox that is introduced with poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (p47phox si_NPs) can alleviate chondrocyte cell death by reducing ROS production. Here, we confirm that p47phox si_NPs significantly attenuated oxidative stress and decreased cartilage damage in mono-iodoacetate (MIA)-induced OA. In conclusion, these data suggest that p47phox si_NPs may be of therapeutic value in the treatment of osteoarthritis.
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The phase behavior of ABC cyclic terpolymer melts is investigated using a simulated annealing technique. A ternary phase diagram is constructed by tuning the volume fractions of the three blocks (fA, fB, and fC) in the case of symmetric interactions. 11 phases are predicted, including lamellae with spheres at the interfaces, lamellae with spheres inside a domain, lamellae with spheres inside domains, cylinders in perforated lamellae, [6.6.6] tiling patterns, lamella + cylinder, hierarchical double-gyroid, columnar piled disk, patched spheres, cylinders with spheres at the interfaces and double gyroid with spheres at the interfaces. In these structures, the end segments of the three blocks tend to distribute uniformly on the A/B, B/C, or A/C interfaces, which may result in superior mechanical properties of the structures in cyclic terpolymer systems than those of the same structures formed in star or linear terpolymer systems. The physical reason for the similarities and differences between the phases formed in ABC cyclic and star terpolymer systems is investigated. Our simulation results are compared with related experimental observations and theoretical calculations.
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Melatonin (MEL) has been demonstrated to exert a protective effect against subarachnoid hemorrhage (SAH), and nitric oxide (NO) has been shown to play an important role in the pathogenesis of vasospasm. This study aims to explore the underlying molecular mechanisms of MEL in the control of vasospasm following SAH. MEL administration attenuates SAH-induced vasospasm and neurobehavioral deficits. Expressions of H19, eNOS, and miR-675 are low in the SAH group, while expressions of miR-138 and HIF1α are high in the SAH group. Also, MEL treatment upon SAH rats completely restores the dysregulation of H19, eNOS, miR-675, miR-138, and HIF1α to their normal levels. Moreover, MEL dose dependently increases the luciferase activity of H19 promoter and hence the expression of H19. Additionally, H19 directly targets miR-675 and miR-138 to increase miR-675 expression and inhibit miR-138 expression. As virtual target genes of miR-675 and miR-138, respectively, HIF1α and eNOS are also regulated by the treatment with MEL. In particular, MEL treatment increases the expression of miR-675 and eNOS level while decreasing the expression of miR-138 and HIF1α in a dose dependent manner. Our study found that MEL ameliorates post-SAH vasospasm by regulating the expression of eNOS and HIF1α via the H19/miR-138/eNOS/NO and H19/miR-675/HIF1α signaling pathways.