ABSTRACT
OBJECTIVE: Many studies have found that miR-26a-5p plays an essential role in the progression of pathological cardiac hypertrophy, however, there is still no evidence on whether miR-26a-5p is related to the activation of autophagy and NLRP3 inflammasome. And the mechanism of miR-26a-5p and NLRP3 inflammasome aggravating pathological cardiac hypertrophy remain unclear. METHODS: Cardiomyocytes were treated with 200µM PE to induce cardiac hypertrophy and intervened with 10mM NLRP3 inhibitor INF39. In addition, we also used the MiR-26a-5p mimic and inhibitor to transfect PE-induced cardiac hypertrophy. RT-qPCR and western blotting were used to detect the expressions of miR-26a-5p, NLRP3, ASC and Caspase-1 in each group, and we used α-SMA immunofluorescence to detect the change of cardiomyocyte area. The expression levels of autophagy proteins LC3, beclin-1 and p62 were detected by western blotting. Finally, we induced the SD rat cardiac hypertrophy model through aortic constriction (TAC) surgery. In the experimental group, rats were intervened with MiR-26a-5p mimic, MiR-26a-5p inhibitor, autophagy inhibitor 3-MA, and autophagy activator Rapamycin. RESULTS: In cell experiments, we observed that the expression of miR-26a-5p was associated with cardiomyocyte hypertrophy and increased surface area. Furthermore, miR-26a-5p facilitated autophagy and activated the NLRP3 inflammasome pathway, which caused changes in the expression of genes and proteins including LC3, beclin-1, p62, ACS, NLRP3, and Caspase-1. We discovered similar outcomes in the TAC rat model, where miR-26a-5p expression corresponded with cardiomyocyte enlargement and fibrosis in the cardiac interstitial and perivascular regions. In conclusion, miR-26a-5p has the potential to regulate autophagy and activate the NLRP3 inflammasome, contributing to the development of cardiomyocyte hypertrophy. CONCLUSION: Our study found a relationship between the expression of miR-26a-5p and cardiomyocyte hypertrophy. The mechanism behind this relationship appears to involve the activation of the NLRP3 inflammasome pathway, which is caused by miR-26a-5p promoting autophagy. Targeting the expression of miR-26a-5p, as well as inhibiting the activation of autophagy and the NLRP3 inflammasome pathway, could offer additional treatments for pathological cardiac hypertrophy.
Subject(s)
Heart Defects, Congenital , MicroRNAs , Rats , Animals , Inflammasomes/genetics , Inflammasomes/metabolism , Myocytes, Cardiac/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Beclin-1/metabolism , Rats, Sprague-Dawley , MicroRNAs/genetics , MicroRNAs/metabolism , Heart Defects, Congenital/metabolism , Cardiomegaly/genetics , Autophagy , Caspases/metabolismABSTRACT
Soils developed in karst regions have naturally high background values of molybdenum (Mo) due to geological factors. However, the enrichment mechanism of Mo in these soils are not fully understood, making it challenging to assess their ecological risk and utilize Mo-rich land resources. To shed light on this issue, this study collected and analyzed data from the 1:50,000 geochemical survey in Guangxi, including 536,503 sets of soil data and 3043 sets of rock data, as well as 40 sets of carbonate rock-soil from typical karst regions. The results showed that soil Mo enrichment is highly correlated with the distribution of carbonate rocks in karst regions. The carbonate rocks in these regions contain Mo ranging from 0.03 to 1.06 mg·kg-1 (with a mean of 0.22 mg·kg-1). In comparison, the soil Mo derived from carbonate rocks can reach up to 6.00 mg·kg-1 (with a mean of 2.75 mg·kg-1), representing an average enrichment of soil Mo that is 24 times higher compared to the carbonate parent rock. The enrichment of soil Mo in karst regions is primarily controlled by secondary enrichment during the weathering process of carbonate. During the insoluble residue accumulation process, the dissolution of carbonate leads to a dramatic reduction in bedrock volume, and the adsorption of clay minerals and Fe minerals in insoluble residues plays an essential role in Mo enrichment during these stages. During the soil-forming stage of the insoluble residue, most Mo leaches into the water body due to the mineral transformation of insoluble residue. Consequently, as Fe-Mn nodules in soils become more enriched with increasing weathering intensity, some Mo is absorbed and passivated by iron and manganese oxides (hydroxides). Accordingly, the contribution of Fe-Mn nodules and the degree of leaching were closely related to the enrichment of soil Mo in karst regions. This study provides insights into the enrichment mechanisms of Mo in soils developed in karst regions, which will help to evaluate their ecological risk in these environments.
Subject(s)
Molybdenum , Soil , Soil/chemistry , China , Environmental Monitoring/methods , Minerals , Carbonates/analysisABSTRACT
With the growing concerns about the Earth's environment and human health, there has been a surge in research focused on the intersection of health and geology. This study quantitatively assesses the relationship between human health and geological factors using a new framework. The framework considers four key geological environment indicators related to health: soil, water, geological landform, and atmosphere. Results indicate that the atmospheric and water resource indicators in the study area were generally favorable, while the scores of geological landforms varied based on topography. The study also found that the selenium content in the soil greatly exceeded the local background value. Our research underscores the importance of geological factors on human health, establishes a new health-geological assessment model, and provides a scientific foundation for local spatial planning, water resource development, and land resource management. However, due to varying geological conditions worldwide, the framework and indicators for health geology may need to be adjusted accordingly.
Subject(s)
Geology , Selenium , Humans , Soil , Atmosphere , Geological PhenomenaABSTRACT
The androgen receptor (AR) poly-glutamine polymorphism (AR-Q) was reported to play role in endometrial cancer (EMCA) development, yet controversial. Environmental factors interact with genetic variation have been reported in EMCA. Aerosol toxins, polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), are EMCA facilitators. This report examined the interplay between AR-Qs and BaP in EMCA. During analysing patient AR-Q polymorphism and Aryl hydrocarbon Receptor (AhR) expressions, we found overall survival (OS) benefit is ascending with AR-Q lengths (5-year OS of 61.3% in Q length <20 and 88% in Q length >23). And AhR is higher expressed in short AR-Q tumour compared to that in long AR-Q patient. In vitro study found androgen-response element (ARE) activity descends with AR-Qs length (Q13 > Q25 > Q35), whereas BaP suppresses ARE activities in EMCA cells. Furthermore, AR-Q13 (but not AR-Q25, or -35) enhances BaP-induced dioxin-responsive element (DRE) activity. Lastly, AR-Q13 exerts higher colony-forming capacity than other AR-Qs, and knock-down AhR abolished AR-Q13-mediated colony numbers. This study demonstrated a possible interaction of gene (AR-Q polymorphism) and environmental toxins (e.g. BaP) to affect cancer progression. A large-scale epidemiology and public health survey on the interaction of environmental toxin and AR poly-Q in EMCA is suggested.
Subject(s)
Endometrial Neoplasms/genetics , Peptides/genetics , Receptors, Androgen/genetics , Receptors, Aryl Hydrocarbon/metabolism , Adult , Aged , Benzo(a)pyrene , Cell Line, Tumor , Cell Proliferation , Disease Progression , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Receptors, Androgen/metabolism , Tumor Stem Cell AssayABSTRACT
BACKGROUND: The purpose of this study was to investigate the therapeutic effects and mechanisms of hyperbaric oxygen (HBO) treatment on rats following spinal cord injury (SCI). METHODS: A total of 45 Sprague-Dawley (SD) rats were randomly divided into three groups. Sham-SCI group was surgically exposed but not subjected to the SCI procedure. SCI-control group was administered SCI and treated with regular air. SCI-HBO group was administered SCI and HBO treatment. Neuromotor functions were examined using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and the inclined plane assessment at before SCI (baseline) and after SCI. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured. RESULTS: Starting from Day 1 after SCI but except Day 2, the SCI-HBO group has significantly higher BBB scores than the SCI-control group. After SCI, the maximum inclination angles at which rats could maintain were significantly lower in both SCI groups. But the maximum angles were significantly bigger for the rats in the SCI-HBO group than those on the SCI-control group at 5, 10 and 20 days after SCI. SOD activities in SCI-HBO rats were significantly higher and MDA levels were significantly lower than in SCI-control rats, at two and five days after SCI. There was also less cystic degeneration of spinal cord in SCI-HBO rats, compared to SCI-control rats. CONCLUSIONS: These results suggest that HBO treatment has a therapeutic value in treating SCI. Increased oxygen free radical scavenging and reduced lipid oxidation may be one of the mechanisms.
Subject(s)
Hyperbaric Oxygenation/methods , Spinal Cord Injuries/therapy , Spinal Cord/pathology , Animals , Female , Rats , Rats, Sprague-DawleyABSTRACT
Previous studies have found that intravenous dexamethasone may produce perineal pruritus in some patients when administered as premedicant in the preoperative period. This randomized controlled, double-blind study evaluated the efficacy of pretreatment of lidocaine on the incidence and severity of dexamethasone-induced perineal pruritus. 400 patients were enrolled in this study and allocated randomly into four groups (n=100, in each). Then, patients received intravenously anesthesia induction as the following sequence of medications: injecting 0.9% sodium chloride (placebo) 10 mL in group I, lidocaine 0.5mg/kg in group II, lidocaine 1mg/kg in group III, and lidocaine 1.5mg/kg in group IV, 1 minute later, injecting 10mg dexamethasone in all groups. The severity of perineal pruritus was graded based on the VAS as none (VAS 0), mild (VAS 1-3), moderate (4-6), or severe (VAS 7 to 10), and recorded the occurrence, the severity and the duration of perineal pruritus. Occurrence of perineal pruritus was significantly reduced in group III and group IV (8%, 9% vs 40% and 33% in Groups I and II, respectively, p<0.05). The incidence of perineal pruritus of females was higher than males in groups I and II (P<0.05). The duration of perineal pruritus was shorter in group IV compared to groups I, II and III (p<0.05). We conclude that pretreatment 1mg/kg or 1.5mg/kg lidocaine may effectively reduce the incidence of perineal pruritus.
Subject(s)
Anesthetics, Local/therapeutic use , Dexamethasone/adverse effects , Lidocaine/therapeutic use , Pruritus/prevention & control , Adult , Anesthesia , Double-Blind Method , Female , Humans , Injections, Intravenous , Male , Middle Aged , Perineum , Pruritus/chemically induced , Sex CharacteristicsABSTRACT
NiO nanocones with good symmetry and highly ordered structure on NiO foil substrate have been successfully fabricated via a facile wet chemical approach combined with subsequent high temperature oxidation. These organized conical superstructures grow only along a certain direction and be controlled via the self-assembly and oriented attachment of a nucleus, which mainly rely on the similar surface energies and the extent of lattice matching of the oriented attached surfaces. During high temperature oxidation, the electric field created via the Ni(2+) and O(2-) facilitates Ni(2+) diffusion outward along the grain boundaries and O(2-) diffusion inward toward to meet the Ni(2+) ions, forming NiO. The as-grown NiO nanocones are 50-350 nm in diameter and 50-400 nm in height. The tip diameter of the nanocone is about 30 nm and the apex angle of the nanocone is about 40°. Meanwhile, we systematically investigated the gas sensing properties of the sensors based on the as-fabricated NiO foil covered with nanocone arrays for ammonia detection at room temperature. The results show that the gas sensing devices have outstanding sensitivity, reproducibility and selectivity, which are mainly because of the excellent connection between the NiO sensing materials and the Au electrodes, the strong electron donating ability of ammonia and the large active surface of selective physisorption for ammonia.
Subject(s)
Ammonia/analysis , Nanoparticles , Nickel/chemistry , Microscopy, Electron, Scanning , X-Ray DiffractionABSTRACT
PRIMARY OBJECTIVE: To determine whether propofol has a neuroprotective effect on hypoxic brain injury. RESEARCH DESIGN: A hippocampal slice, in artificial cerebrospinal fluid (ASCF) with glucose and oxygen deprivation (OGD), was used as an in vitro model for brain hypoxia. METHODS AND PROCEDURES: The orthodromic population spike (OPS) and hypoxic injury potentia1 (HIP) were recorded in the CA1 region when Schaffer collateral was stimulated in the CA3 region of the hippocampal slices during hypoxia. The concentrations of amino acid neurotransmitters in perfusion solution of hippocampal slices were directly measured using high performance liquid chromatography (HPLC). Morphological changes of neurons, astrocytes and mitochondria in CA1 region were observed using histology and electron microscopy. Neuronal apoptosis was evaluated with TUNEL assay. MAIN OUTCOME AND RESULTS: Propofol treatment delayed the elimination of OPS and improved the recovery of OPS; decreased frequency of HIP, postponed the onset of HIP and increased the duration of HIP. Propofol treatment also decreased the release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but elevated the release of γ-aminobutyric acid (GABA). Morphological studies showed that propofol treatment attenuated oedema of pyramid neurons in the CA1 region and reduced apoptosis. CONCLUSIONS: Propofol has a neuro-protective effect on hippocampal neuron injury induced by hypoxia.
Subject(s)
Glutamic Acid/metabolism , Hippocampus/drug effects , Hypoxia, Brain/drug therapy , Neuroprotective Agents/pharmacology , Propofol/pharmacology , gamma-Aminobutyric Acid/metabolism , Animals , Hippocampus/metabolism , Hypoxia, Brain/metabolism , In Vitro Techniques , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To explore the potential effect of ultrasound-guided stellate ganglion block (SGB) on lung protection for patients undergoing one-lung ventilation (OLV). METHODS: A total of 123 patients undergoing elective one-lung ventilation surgery were selected as research subjects in this prospective study. These patients were randomly divided into the SGB group, control group and blank group on average. Stellate ganglion block was carried out in the SGB and control groups. Patients in the SGB group were injected with 6 ml mixture of 0.25% ropivacaine hydrochloride and 1% lidocaine hydrochloride, while those in the control group were injected with 6 mL of 0.9% saline. Punctures weren't performed for patients in the blank group. The same induction and maintenance of general anesthesia was adopted for all three groups. Hemodynamics, respiratory parameters and arterial blood gas analysis were recorded after entering the operation room (T0), pre-OLV (T1), 30 min after OLV (T2), 60 min after OLV (T3), at the end of surgery (T4), and 30 min after extubation (T5). Oxygenation index (OI), pulmonary shunt fraction (Qs/Qt) and pH value were compared at different time points. Intravenous serum was collected at T0, T3 and T5 for the detection of surfactant proteins A (SP-A), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6) and interleukin-10 (IL-10) levels, respectively. The complications related to SGB after surgery and the postoperative pulmonary complications within 72 h were recorded. RESULTS: At T1, T2, and T3, MAP level in SGB group was lower than that in blank and control groups (P<0.05). At T2, and T3, SGB group had lower hear rate (HR), peak airway pressure (Ppeak) and tidal volume (TV) than blank and control groups (all P<0.05). From T2 to T5, SGB group had higher OI but lower Qs/Qt than blank and control groups (both P<0.05). At T3 and T5, SGB group had lower SP-A, IL-6, and MDA levels but higher IL-10 and SOD levels than blank and control groups (all P<0.05). There was one case of hypoxemia in the blank group within 72 h after surgery. CONCLUSION: Ultrasound-guided SGB has lung-protective effects on patients undergoing OLV, which significantly improves patients' OI, reduces intrapulmonary shunts, declines ventilator-induced lung damage, and inhibits inflammatory response as well as oxidative stress (China Clinical Trial Registry, registration number ChiCTR2000033385, https://www.chictr.org.cn).
ABSTRACT
The selenium (Se)-deficient soil belt in China has gained widespread attention. During large-scale soil surveys in China, Se-rich soils within low-Se belts have been identified. However, the sources of Se in those soils and the controlling factors for their enrichment remain unclear. Here we summarize Se concentrations and spatial distributions in the Yuanzhou district of the Loess Plateau. We evaluated Se variations in soil profiles, Se migration into water bodies, and considered soil indicators, topographic characteristics and the influence of land-use types on soil Se concentrations. The average Se concentration in the topsoil of the Yuanzhou district was 0.164 µg/g. High-Se soils (>0.222 µg/g) were found in the western valley plain and the southern red bed hilly area, as well as sporadically in higher elevation forestland and grassland areas in the east. Enrichment of Se in the topsoil in the eastern and southern areas was primarily due to Se adsorption and accumulation by soil organic matter as well as enrichment in gypsum, berlinite, and clay minerals during soil formation. Widespread enrichment in the southern area was linked to high Se concentrations in red Tertiary sedimentary rocks. In the western area, enrichment of Se in topsoil was found on both sides of the Qingshui River at low elevations with gentle slopes, with river water being the primary carrier of Se enrichment. These findings provide valuable insights into the epigenetic geochemical behavior of soil Se in China's low-Se belt that accounts for development of Se-rich soils in the region.
Subject(s)
Selenium , Soil , China , Forests , WaterABSTRACT
OBJECTIVE: To detect mRNA and protein expression of meiosis-specific genes in human umbilical cord mesenchymal stem cells (hUMSCs) in an in vitro co-culture microenvironment with mouse primordial germ cells (PGCs), and to further explore the effective potential of hUMSCs to differentiate into PGCs. METHODS: HUMSCs were obtained from human Wharton's jelly fragments by adherent culture. PGCs were derived from 12.5 days post-coitum (dpc) BalbC mice. Then hUMSCs were co-cultured with PGCs in Matrigel, inside or outside of a culture chamber, respectively. The changes in morphology and cytogenetic characteristics were observed. SCP3 and DDX4 expression in hUMSCs were detected and analyzed using immunofluorescence staining. Oct-4, Stra8, Zp3 and Dmc1 gene expressions in PGCs, hUMSCs, and hUMSCs after co-culture with PGCs were analyzed by real time reverse transcription-polymerase chain reaction. RESULTS: Both hUMSCs and PGCs expressed Oct-4 at different degrees. After co-culture with PGCs, hUMSCs became rounded and showed AKP activity. HUMSCs suspension-cultured in Matrigel or adherent cultured with cell chamber significantly expressed Stra8, DMC1, SCP3 and DDX4 genes. CONCLUSION: HUMSCs can be induced to express PGC-specific genes Stra8 and DMC1, spermatogonium/oogonium-specific genes SCP3 and DDX4 that predict directed differentiation potential into early germ cells at a molecular level.
ABSTRACT
The exact cause of complete endocardial cushion defect (ECD) is still unknown. This report describes a unique pair of monozygotic twins (MZ twins) discordant for ECD. The chromosome karyotyping analysis revealed normal karyotype of 46, XY, 16qh+ and mat in both MZ twins. A genome-wide analysis of DNA using the Affymetrix SNP 6.0 revealed identical genotyping of single nucleotide polymorphisms (SNPs) and copy number variations (CNVs). An extensive methylation assay was carried out by NimbleGen 3 × 720 K CpG Island Plus RefSeq Promoter Arrays to analyze the potential epigenetic differences. The DNA methylation profiles of the affected twin seemed increased compared with that of the unaffected twin. However, further validation of Notch1 promoter hypermethylation and six top-ranked differentially methylated CpG sites by sodium bisulfate modification and methylation-specific PCR, failed to reveal consistent methylation differences between the twins. Other relevant factors, such as heritability and penetrance of the condition that place the MZ twins near to a threshold for ECD or variations in local epigenetic events in the twins' heart tissues, are probably responsible for the phenotypic discordance.
ABSTRACT
As training high-performance object detectors requires expensive bounding box annotations, recent methods resort to free-available image captions. However, detectors trained on caption supervision perform poorly because captions are usually noisy and cannot provide precise location information. To tackle this issue, we present a visual analysis method, which tightly integrates caption supervision with object detection to mutually enhance each other. In particular, object labels are first extracted from captions, which are utilized to train the detectors. Then, the objects detected from images are fed into caption supervision for further improvement. To effectively loop users into the object detection process, a node-link-based set visualization supported by a multi-type relational co-clustering algorithm is developed to explain the relationships between the extracted labels and the images with detected objects. The co-clustering algorithm clusters labels and images simultaneously by utilizing both their representations and their relationships. Quantitative evaluations and a case study are conducted to demonstrate the efficiency and effectiveness of the developed method in improving the performance of object detectors.
ABSTRACT
Artificial intelligence (AI) based on the perspective of data elements is widely used in the healthcare informatics domain. Large amounts of clinical data from electronic medical records (EMRs), electronic health records (EHRs), and electroencephalography records (EEGs) have been generated and collected at an unprecedented speed and scale. For instance, the new generation of wearable technologies enables easy-collecting peoples' daily health data such as blood pressure, blood glucose, and physiological data, as well as the application of EHRs documenting large amounts of patient data. The cost of acquiring and processing health big data is expected to reduce dramatically with the help of AI technologies and open-source big data platforms such as Hadoop and Spark. The application of AI technologies in health big data presents new opportunities to discover the relationship among living habits, sports, inheritances, diseases, symptoms, and drugs. Meanwhile, with the development of fast-growing AI technologies, many promising methodologies are proposed in the healthcare field recently. In this paper, we review and discuss the application of machine learning (ML) methods in health big data in two major aspects: (1) Special features of health big data including multimodal, incompletion, time validation, redundancy, and privacy. (2) ML methodologies in the healthcare field including classification, regression, clustering, and association. Furthermore, we review the recent progress and breakthroughs of automatic diagnosis in health big data and summarize the challenges, gaps, and opportunities to improve and advance automatic diagnosis in the health big data field.
ABSTRACT
Black shale is rich in potentially toxic elements (PTEs) that migrate through rock weathering or rainfall, adversely affecting human health and the environment. In this study, simulated rainfall leaching experiments were used to investigate the migration patterns and leaching kinetics of PTEs in black shale from the Lower Cambrian Hetang Formation and to analyze the water quality index (WQI) of PTEs in the leachate. A comparison between the risk of PTEs in the leachate and those in the soil was also made to determine the risk sources, risk status, and distribution characteristics of PTEs in the study area. The WQI of the indoor column experimental leachate indicated the highest As contamination. The geo-accumulation index (Igeo) and potential ecological risk (Er) of soils in the entire region revealed that the risk of Cd was the highest. Furthermore, by mapping the distribution of Igeo and Er in soils, the risk level in the region where black shale is located was found to be significantly higher than that in other areas. Comparing the leaching rate of PTEs with the WQI from leaching experiments, the risk associated with As in soil can be inferred to originate mainly from the leaching of black shale. Previous studies on PTEs in black shale in the study area tended to focus on Cd; however, this study found that the risk of As was not negligible. The health risk assessment also showed that the risk at the location of black shale was beyond the accepted range. Overall, this study provided a new and important evaluation law for the level of pollution by PTEs and health risks in typical black shale regions.
Subject(s)
Metals, Heavy , Soil Pollutants , Cadmium , China , Environmental Monitoring , Humans , Metals, Heavy/analysis , Minerals , Risk Assessment , Soil , Soil Pollutants/analysisABSTRACT
In Location-Based Social Networks (LBSNs), registered users submit their reviews for visited point-of-interests (POIs) to the system providers (SPs). The SPs anonymously publish submitted reviews to build reputations for POIs. Unfortunately, the user profile and trajectory contained in reviews can be easily obtained by adversaries who SPs has compromised with. Even worse, existing techniques, such as cryptography and generalization, etc., are infeasible due to the necessity of public publication of reviews and the facticity of reviews. Inspired by pseudonym techniques, we propose an approach to exchanging reviews before users submit reviews to SPs. In our approach, we introduce two attacks, namely review-based location correlation attack (RLCA) and semantic-based long-term statistical attack (SLSA). RLCA can be exploited to link the real user by reconstructing the trajectory, and SLSA can be launched to establish a connection between locations and users through the difference of semantic frequency. To resist RLCA, we design a method named User Selection to Resist RLCA (USR-RLCA) to exchange reviews. We propose a metric to measure the correlation between a user and a trajectory. Based on the metric, USR-RLCA can select reviews resisting RLCA to exchange by suppressing the number of locations on each reconstructed trajectory below the correlation. However, USR-RLCA fails to resist SLSA because of ignoring the essential semantics. Hence, we design an enhanced USR-RLCA named User Selection to Resist SLSA (USR-SLSA). We first propose a metric to measure the indistinguishability of locations concerning the difference of semantic frequency in a long term. Then, USR-SLSA can select reviews resisting SLSA to exchange by allowing two reviews whose indistinguishability is below the probability difference after the exchange to be exchanged. Evaluation results verify the effectiveness of our approach in terms of privacy and utility.
Subject(s)
Algorithms , Computer Security , Privacy , Social Networking , HumansABSTRACT
BACKGROUND: It is believed that preemptive IV lornoxicam treatment can reduce the consumption of other analgesics, improve analgesic efficacy, and ameliorate immune function during patient-controlled IV analgesia. However, the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of patient-controlled epidural analgesia (PCEA) with morphine and on chemokine expression remain unknown. OBJECTIVE: The aim of this prospective, randomized, controlled study was to observe the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of PCEA with morphine and on the expression of monocyte chemotactic protein-1 (MCP-1) and stromal cell-derived factor-1α (SDF-1α) in women undergoing hysterectomy. METHODS: Patients undergoing elective hysterectomy with combined spinal and epidural anesthesia were randomized to 1 of 3 groups to receive IV lornoxicam 8 mg before anesthesia (group 1), lornoxicam 16-mg injection before anesthesia (group 2), or isotonic saline (control) before anesthesia. PCEA was used to treat postoperative pain, and a visual analog scale (VAS) and the Bruggemann Comfort Scale (BCS) were used to evaluate analgesic efficacy. Morphine consumption was recorded. To measure plasma concentrations of MCP-1 and SDF-1α via enzyme-linked immunosorbent assay, venous blood samples were obtained from patients at 4 separate times: before anesthesia (baseline); 0 (immediately after anesthesia administration); and 24 and 48 hours after surgery. RESULTS: Forty-five patients (mean [SD] age, 41 [5] years; mean [SD] weight, 54 [6] kg) undergoing elective hysterectomy were included in the study. There were no significant differences in VAS scores, BCS scores, or morphine consumption between the 3 groups. Compared with baseline values, MCP-1 and SDF-1α concentrations were increased significantly immediately after surgery in all 3 groups (all, P < 0.01) and returned to near-baseline values at 24 hours postsurgery in groups 1 and 2, and by 48 hours postsurgery in the control group. MCP-1 and SDF-1α concentrations in groups 1 and 2 were significantly lower than those in the control group immediately (all, P < 0.01) and 24 hours postsurgery (all, P < 0.05). CONCLUSION: Preemptive IV lornoxicam treatment was associated with attenuation of the plasma concentrations of MCP-1 and SDF-1α immediately after and 24 hours after hysterectomy and was associated with more rapid resolution to near-baseline concentrations of both cytokines in these patients compared with controls; however, it was not associated with significantly reducing epidural morphine consumption.
ABSTRACT
Glucocorticoid-induced osteoporosis (GIOP) is a serious clinical bone disease that results from the long-term consumption of glucocorticoids or glucocorticoid-like drugs. Although many studies have attempted to determine the mechanisms of GIOP, they are still unclear. In this study, we established a zebrafish model of glucocorticoid-like drug-induced osteoporosis by treating larvae with prednisolone. We then quantified the expression of a selection of extracellular matrix (ECM)-, osteoblast-, and osteoclast-related genes. Our results showed that at 15 days post fertilization, zebrafish larvae treated with 25⯵M prednisolone are a suitable model for GIOP, not only owing to the decrease in robust bone mass but also because of significant alterations in gene expression. The quantification of the expression of ECM-, osteoblast-, and osteoclast- related genes revealed that mmp9 and mmp13 were significantly upregulated and entpd5a, acp5a, and sost were significantly downregulated. These genes may be a target for future research into GIOP. Our study thus provides new insights into GIOP.
Subject(s)
Osteoporosis/chemically induced , Osteoporosis/pathology , Prednisolone/adverse effects , Zebrafish/metabolism , Animals , Extracellular Matrix/genetics , Extracellular Matrix/metabolism , Gene Expression Regulation/drug effects , Larva/drug effects , Osteoblasts/drug effects , Osteoblasts/metabolism , PhenotypeABSTRACT
Estrogen can affect the cartilage development of zebrafish; however, the mechanism underlying its effects is not completely understood. Four-day-old zebrafish larvae were treated with 0.8⯵M estrogen, the 5â¯days post fertilization (dpf) zebrafish larvae did not demonstrate obvious abnormalities during development; however, the 6 dpf and 7 dpf larvae exhibited abnormal craniofacial bone development along with craniofacial bone degradation. RNA deep sequencing was performed to elucidate the mechanism involved. Gene Ontology functional and KEGG pathway enrichment analysis of differentially expressed genes (DEGs) showed that the extracellular matrix (ECM), extracellular region, ECM-interaction receptor, focal adhesion, cell cycle, apoptosis, and bone-related signaling pathways were disrupted. In these signaling pathways, the expressions of key genes, such as collagen encoded (col19a1a, col7a1, col7al, col18a1, and col9a3), MAPK signaling pathway (fgf19, fgf6a), TGF-beta signaling pathway (tgfbr1), and cell cycle (cdnk1a) genes were altered. The qRT-PCR results showed that after treatment with 0.8⯵M 17-ß estradiol (E2), col19a1a, col7a1, col7al, col18a1, col9a3, fgf6a, cdkn1a were downregulated, and fgf19, tgfr1 were upregulated, which were consistent with deep sequencing analysis. Therefore, the effect of estrogen on cartilage development might occur via multiple mechanisms. The study results demonstrate the mechanism underlying the effect of estrogen on cartilage development.
Subject(s)
Cartilage/drug effects , Chondrogenesis/drug effects , Craniofacial Abnormalities/chemically induced , Estrogens/adverse effects , Gene Expression Regulation, Developmental/drug effects , Models, Biological , Teratogens/toxicity , Animals , Apoptosis/drug effects , Bone Development/drug effects , Bone Resorption/chemically induced , Bone Resorption/metabolism , Cartilage/abnormalities , Cartilage/metabolism , Cell Cycle/drug effects , Collagen/genetics , Collagen/metabolism , Craniofacial Abnormalities/metabolism , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Gene Expression Profiling , Gene Ontology , High-Throughput Nucleotide Sequencing , Larva , Signal Transduction/drug effects , Zebrafish , Zebrafish Proteins/chemistry , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolismABSTRACT
Acute lung injury (ALI) is a disturbance caused by infectious or non-infectious inflammation and lipopolysaccharide (LPS) could induce an artificial pathological ALI process. Sevoflurane has been demonstrated to be an inhaled anesthetic having anti-inflammatory and protective effects on inflammatory injury. To study the protective effects and mechanisms of sevoflurane on LPS-induced acute lung injury in mice. By assessing W/D ratio, sevofluranecan counteract the edema induced by LPS. The ELISA results showed that sevoflurane reduced IFN-γ production and increased IL-10 level. Elevation of PGE2 induced by sevofluraneand LPS in peritoneal macrophages was inhibited by NS-398, an inhibitor of the PGE2 regulator COX-2, indicating that NS-398 blocked COX-2 mediated PGE2 synthesis. NS-398 itself did not cause lung inflammation and mitigated the protective effect of sevoflurane on LPS-induced ALI in mice. LPS changes immune homeostasis, resulting in acute lung inflammatory injury. Inhaled sevoflurane regulates immune homeostasis, thereby playing a protective role in alleviating LPS-induced ALI.