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In this work, we constructed theoretical models by embedding Fe-TCPP and Fe-(mIM)n (n = 2,3,4) active sites into hole-graphene, and the structural stability was evaluated using molecular dynamics simulations. Based on the theoretical models, we systematically studied the oxygen reduction reaction (ORR) mechanism and the effect of spatial confinement and ligands with DFT calculations. The analysis of the ORR reaction pathway shows that Fe-TCPP and Fe-(mIM)4 have good catalytic activity. Subsequently, the confinement effect (5-14 Å) was introduced to investigate its influence on the catalytic activity. The Fe-TCPP and Fe-(mIM)4 active sites have the lowest overpotential at an axial space of 8 Å and 9 Å, respectively. We select four ligands (bpy, pya, CH3, and bIm) to explore their effect on the catalytic activity of the Fe-TCPP active site. With the modification of bpy, pya, and bIm_N (Fe-N4 sites become Fe-N5 active sites), the overpotential decreases by 26-31%. In the present work, the best catalytic system is Fe-TCPP_pya, which is on the top of the volcano plot.
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BACKGROUND: Granulosa cell (GC) proliferation and apoptosis are critical events of the ovum energy supply, which lead to follicular growth retardation or atresia, and various ovulatory obstacles, eventually resulting in the development of ovarian disorders such as polycystic ovarian syndrome (PCOS). Apoptosis and dysregulated miRNA expression in GCs are manifestations of PCOS. miR-4433a-3p has been reported to be involved in apoptosis. However, there is no study reporting the roles of miR-4433a-3p in GC apoptosis and PCOS progression. METHODS: miR-4433a-3p and peroxisome proliferator-activated receptor alpha (PPAR-α) levels in GCs of PCOS patients or in tissues of a PCOS rat model were examined by quantitative polymerase chain reaction and immunohistochemistry. Bioinformatics analyses and luciferase assays were used to examine the association between miR-4433a-3p and PPAR-α, as well as PPAR-α and immune cell infiltration, in PCOS patients. RESULTS: miR-4433a-3p expression in GCs of PCOS patients was increased. miR-4433a-3p overexpression inhibited the growth of the human granulosa-like tumor cell line (KGN) and promoted apoptosis, while co-treatment with PPAR-α and miR-4433a-3p mimic rescued miR-4433a-3p-induced apoptosis. PPAR-α was a direct target of miR-4433a-3p and its expression was decreased in PCOS patients. PPAR-α expression was also positively correlated with the infiltration of activated CD4+ T cells, eosinophils, B cells, gamma delta T cells, macrophages, and mast cells, but negatively correlated with the infiltration of activated CD8+ T cells, CD56+ bright natural killer cells, immature dendritic cells, monocytes, plasmacytoid dendritic cells, neutrophils, and type 1 T helper cells in PCOS patients. CONCLUSION: The miR-4433a-3p/PPAR-α/immune cell infiltration axis may function as a novel cascade to alter GC apoptosis in PCOS.
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MicroRNAs , Síndrome do Ovário Policístico , Feminino , Humanos , Ratos , Animais , PPAR alfa/genética , PPAR alfa/metabolismo , Síndrome do Ovário Policístico/patologia , Células da Granulosa/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genética , Proliferação de Células/genéticaRESUMO
Osteoporosis (OP) is one of the most common bone disorders among the elderly, characterized by abnormally elevated bone resorption caused by formation and activation of osteoblast (OC). Excessive reactive oxygen species (ROS) accumulation might contribute to the formation process of OC as an essential role. Although accumulated advanced treatment target on OP have been proposed in recent years, clinical outcomes remain unexcellence attributed to severe side effects. The purpose of present study was to explore the underlying mechanisms of GSK 650394 (GSK) on inhibiting formation and activation of OC and bone resorption in vitro and in vivo. GSK could inhibit receptor activator of nuclear-κB ligand (RANKL-)-mediated Oc formation via suppressing the activation of NF-κB and MAPK signaling pathways, regulating intracellular redox status, and downregulate the expression of nuclear factor of activated T cells c1 (NFATc1). In addition, quantitative RT-PCR results show that GSK could suppress the expression of OC marker gene and antioxidant enzyme genes. Consistent with in vitro cellular results, GSK treatment improved bone density in the mouse with ovariectomized-induced bone loss according to the results of CT parameters, HE staining, and Trap staining. Furthermore, GSK treatment could enhance the capacity of antioxidant enzymes in vivo. In conclusion, this study suggested that GSK could suppress the activation of osteoclasts and therefore maybe a potential therapeutic reagent for osteoclast activation-related osteoporosis.
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Benzoatos , Reabsorção Óssea , Compostos Bicíclicos Heterocíclicos com Pontes , Osteoclastos , Osteoporose , Animais , Benzoatos/farmacologia , Benzoatos/uso terapêutico , Reabsorção Óssea/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Ligante RANK/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Objective: Hounsfield Unit (HU) has been used to investigate the asymmetrical vertebral bone mass in patients associated with adult degenerative scoliosis (ADS). Therefore, there is an inevitable need to evaluate the performance of HU values in ADS subjects. Methods: A total of 162 patients (81 ADS patients and 81 non-ADS patients) aged ≥50 years undergoing the CT examination were reviewed. The HU values of the lumbar vertebral body (including total, convex side, and concave side) at bilateral pedicle plane were obtained and compared. The paired t-test, chi-squared test, independent samples t-test, and interclass correlation coefficient (ICC) were used for statistical analyses. Results: The HU values were significantly different between the convex and concave sides of the lumbar vertebral body (P < 0.01). The total prevalence of osteoporosis (OP) in ADS patients was higher than that of non-ADS patients. The prevalence of OP in female or male of ADS patients was higher than that of non-ADS patients, respectively. Intra- and inter-rater reliability were very strong (both >0.8) for measuring asymmetrical vertebral bone mass in ADS patients. Conclusion: HU value was a high reproducibility method for evaluating the vertebral bone mass in ADS patients. The HU values at the concave sides were significantly higher than that of convex sides at the lumbar vertebral body on the pedicle plane. The prevalence of OP in ADS patients was higher than that of non-ADS patients, especially for females associated with ADS. Moreover, the static asymmetric load did not enhance the bone mass at the concave side compared with the left/right side of non-ADS patients.
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Osteoporosis occurs in astronauts after long-term space flight owing to the lack of gravity. The mechanical microenvironment of osteocytes in load-bearing bone are changed during resistance exercise, which prevents massive bone loss in the human body. A cylindrical fluid-structure coupling finite element model for osteons with a two-stage pore structure (i.e., Haversian canal, lacunar-canalicular system) was established with the software COMSOL. In the Earth's gravity field and in microgravity, considering the effects of pulsating pressure of arterioles, a comparative study was performed on the changes in hydrodynamic microenvironment of osteocytes during human body high-intensity exercise at different frequencies (defined as causing bone to produce 3000 µÎµ) and the body is at rest. Positive and negative liquid pressure (with respect to one atmosphere pressure) alternately acted on osteocytes during human exercising, but only positive pressure acted on osteocytes during human resting. The variation range of liquid pressure acted on osteocytes during human exercising was significantly higher than that during resting. The liquid flow velocity around osteocytes during body exercise was about four orders of magnitude higher than that during resting. In microgravity, moderate physical exercise can obviously improve the hydrodynamic microenvironment of osteocytes in load-bearing bone, which could compensate for the lack of mechanical stimulation to osteocytes caused by the lack of gravity, thereby promoting the normal physiological function of osteocytes. To a certain extent, these results revealed the biomechanical mechanism by which exercise has an effect in fighting osteoporosis in astronauts.
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Osteoporose , Treinamento Resistido , Ausência de Peso , Humanos , Osteócitos/fisiologia , Hidrodinâmica , Exercício FísicoRESUMO
STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the effects of percutaneous transforaminal endoscopic decompression (PTED) for lumbar stenosis associated with adult degenerative scoliosis and to analyze the correlation between preoperative radiological parameters and postoperative surgical outcomes. METHODS: Two years of retrospective data was collected from 46 patients with lumbar stenosis associated with adult degenerative scoliosis who underwent PTED. The visual analog scale (VAS), Oswestry Disability Index, and modified MacNab criteria were used to evaluate the clinical outcomes. Multiple linear regression analysis was used to analyze the correlation between radiological parameters and surgical outcomes. RESULTS: The mean age of the 33 female and 13 male patients was 73.5 ± 8.1 years. The mean follow-up was 27.6 ± 3.5 months (range from 24 to 36). The average coronal Cobb angle was 24.5 ± 8.2°. There were better outcomes of the VAS for leg pain and Oswestry Disability Index after surgery. Based on the MacNab criteria, excellent or good outcomes were noted in 84.78% of patients. Multiple linear regression analysis showed that Cobb angle and lateral olisthy may be the predictors for low back pain. CONCLUSION: Transforaminal endoscopic surgery may be an effective and safe method for geriatric patients with lumbar stenosis associated with degenerative scoliosis. The predictive factors of clinical outcomes were severe Cobb angle and high degree lateral subluxation. Transforaminal endoscopic surgery may not be recommended for patients with Cobb angle larger than 30° combined with lateral subluxation.
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The absence of leptin results in contrasting growth pattern of appendicular and axial bone growth in ob/ob mice. Endochondral bone formation is an important procedure of growth plate determining the bone growth, where this procedure is also regulated by estrogen and its receptor (ER) signaling pathway. The present study is undertaken to explore the roles of ERs in regulating the different growth patterns in ob/ob mice. In this study, C57BL/6 female mice were used as wild-type (WT) mice; ob/ob mice and WT mice were age-matched fed, and bone length is analyzed by X-ray plain film at the 12 weeks old. We confirm that ob/ob mice have shorter femoral length and longer spine length than WT mice (p < 0.05). The contrasting expression patterns of chondrocyte proliferation proteins and hypertrophic marker proteins are also observed from the femur and spinal growth plate of ob/ob mice compared with WT mice (p < 0.01). Spearman's analysis showed that body length (axial and appendicular length) is positively related to the expression level of ERα in growth plate. Three-week-old female ob/ob mice are randomized divided into three groups: 1) ob/ob + ctrl, 2) ob/ob + ERα antagonist (MPP), and 3) ob/ob + ERß antagonist (PHTPP). Age-matched C57BL/6 mice were also divided into three groups, same as the groups of ob/ob mice. MPP and PHTPP were administered by intraperitoneal injection for 6 weeks. However, the results of X-ray and H&E staining demonstrate that leptin deficiency seems to disturb the regulating effects of ER antagonists on longitudinal bone growth. These findings suggested that region-specific expression of ERα might be associated with contrasting phenotypes of axial and appendicular bone growth in ob/ob mice. However, ER signaling on longitudinal bone growth was blunted by leptin deficiency in ob/ob mice, and the underlying association between ERs and leptin needs to be explored in future work.
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Desenvolvimento Ósseo/efeitos dos fármacos , Receptor alfa de Estrogênio/antagonistas & inibidores , Fêmur/efeitos dos fármacos , Piperidinas/farmacologia , Pirazóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Moduladores de Receptor Estrogênico/farmacologia , Camundongos , Camundongos Obesos , Pirimidinas/farmacologiaRESUMO
BACKGROUND: Gestational diabetes mellitus (GDM) is associated with a heightened level of oxidative stress, which is characterized by the overproduction of reactive oxygen species (ROS) from mitochondria. Previous studies showed that mitochondrial dysfunction is regulated by dynamin-related protein 1 (Drp1) and p66Shc in GDM. AIM: The aim was to investigate the expression of Drp1 and p66Shc and their possible mechanisms in the pathogenesis of GDM. METHODS: A total of 30 pregnant women, 15 with GDM and 15 without GDM, were enrolled. Peripheral blood mononuclear cells and placental tissue were collected. The human JEG3 trophoblast cell line was cultivated in 5.5 mmol/L or 30 mmol/L glucose and transfected with wild-type (wt)-p66Shc and p66Shc siRNA. P66Shc and Drp1 mRNA levels were detected by quantitative real-time polymerase chain reaction. The expression of p66Shc and Drp1 was assayed by immunohistochemistry and western blotting. ROS was assayed by dihydroethidium staining. RESULTS: The p66Shc mRNA level was increased in the serum (P < 0.01) and placentas (P < 0.01) of women with GDM, and the expression of Drp1 mRNA and protein were also increased in placentas (P < 0.05). In JEG3 cells treated with 30 mmol/L glucose, the mRNA and protein expression of p66Shc and Drp1 were increased at 24 h (both P < 0.05), 48 h (both P < 0.01) and 72 h (both P < 0.001). ROS expression was also increased. High levels of Drp1 and ROS expression were detected in JEG3 cells transfected with wt-p66Shc (P < 0.01), and low levels were detected in JEG3 cells transfected with p66Shc siRNA (P < 0.05). CONCLUSION: The upregulated expression of Drp1 and p66shc may contribute to the occurrence and development of GDM. Regulation of the mitochondrial fusion-fission balance could be a novel strategy for GDM treatment.
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BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine-related follicular developmental disorder that affects 50 %-70 % of reproductive-aged women diagnosed with ovulation-related infertility. Abnormal proliferation and apoptosis of granulosa cells (GCs) are thought to be the critical factors leading to abnormal maturation of follicles. It has been shown that microRNAs (miRNAs) exert a significant influence in the pathogenesis of PCOS; however, the relationship between miRNA, PCOS, and GC apoptosis is not entirely understood. METHODS: To clarify the effect of miR-194 in PCOS, CCK-8, Ki67 staining, AO/EB, and flow cytometry assays were used to assess cell growth, proliferation, and apoptosis in KGN cells, which were artificially stimulated to overexpress miR-194. Luciferase reporter assays and rescue experiments were used to elucidate the mechanism underlying miR-194 in PCOS. RESULTS: miR-194 expression was significantly up-regulated in rat models of PCOS and the ovarian GCs of PCOS patients. miR-194 suppression promoted KGN cell growth and proliferation. miR-194 overexpression also induced cell apoptosis, while miR-194 downregulation had an opposite effect. Furthermore, up-regulating heparin-binding EGF-like growth factor (HB-EGF) expression rescued the pro-apoptotic effects of miR-194 upregulation on KGN cells. CONCLUSIONS: miR-194 is increased in PCOS granulosa cell and may function as a novel biomarker and therapeutic target for KGN cells via HB-EGF regulation.
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Apoptose/fisiologia , Tumor de Células da Granulosa/metabolismo , Células da Granulosa/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/biossíntese , MicroRNAs/biossíntese , Síndrome do Ovário Policístico/metabolismo , Adulto , Animais , Linhagem Celular , Proliferação de Células/fisiologia , Feminino , Tumor de Células da Granulosa/patologia , Células da Granulosa/patologia , Humanos , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Sprague-Dawley , Adulto JovemRESUMO
OBJECTIVE: Publications on hidden blood loss (HBL) after posterior lumbar interbody fusion (PLIF) for lumbar spine stenosis syndrome (LSS) have been reported, but the modified HBL (mHBL) was different from HBL obtained by classical formula and there are few studies on lumbar spine hemorrhage with rheumatoid arthritis (RA). Therefore, the aim of our study is to respectively evaluate the importance of hidden blood loss (HBL) and modified HBL (mHBL) after posterior lumbar interbody fusion (PLIF) in patients diagnosed with LSS and RA, to explore the correlation between RA activity and HBL as well as mHBL. METHODS: A total of 61 patients (nine males and 52 females) diagnosed with LSS and RA who underwent PLIF were included. Data contained demographics, RA-related parameters such as duration of RA, Steinbrocker classification (used to evaluated RA activity), the disease-modifying anti-rheumatic drugs (DMARDs), osteoporosis and total knee arthroplasty; operation and hemorrhage parameters. Then HBL and mHBL were calculated by Gross formula and modified formula, respectively. Subgroup analysis on HBL and mHBL was performed based on gender, age (≤60 years and Ë60 years), different number of surgical segments (single segment, double segment, and ≥3 segments), and taking DMARDs or not. ANOVA analysis was performed on HBL and mHBL in different surgery segment number and Steinbrocker classification of RA. Independent sample t-test was used in comparison of gender and age, as well as in comparison between HBL and mHBL based on whether the patient took DMARDs or not. Furthermore, paired t-test was used to compare the volume between HBL and mHBL. RESULTS: The mean age and duration of RA was 65.2 ± 9.3 years and 14.3 ± 10.7 years, respectively. There were 13 grade I cases, 34 grade II cases, and 14 grade III cases as assessed by Steinbrocker classification and the most common anti-RA drugs were DMARDs (57.4%). The mean intraoperative bleeding, drainage, and blood loss in drainage (DBL) was 453.3 ± 377.8 mL, 489.1 ± 253.8 mL, and 304.6 ± 156.3 mL, respectively. There was no difference on HBL and mHBL in gender. HBL and mHBL was larger in patients over 60 years (P = 0.040 and P = 0.023). There were differences in intraoperative blood loss, drainage, and DBL based on different number of segments but not in HBL and mHBL, or on Steinbrocker classification. DBL was lower in DMARDs group than non-drugged group (P = 0.03), while HBL and mHBL were both of no significance. The comparison of HBL and mHBL showed statistical difference (P < 0.001), suggesting that mHBL volume is larger than HBL. CONCLUSIONS: Patients diagnosed as LSS with RA have amounts of HBL or mHBL after PLIF. HBL or mHBL is not associated with RA activity, which may not increase in RA patients compared with common ones. Taking DMARDs may reduce postoperative DBL. The fact that mHBL is larger than HBL provides an all-round basis for measuring factual HBL.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Perda Sanguínea Cirúrgica , Vértebras Lombares/cirurgia , Hemorragia Pós-Operatória , Fusão Vertebral/métodos , Estenose Espinal/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Estrogen receptors (ERs) regulate the development of the growth plate (GP) by binding to estrogen, a phenomenon that determines the growth of skeletal bone. However, the exact mechanisms underlying the regulatory effects of ERs on axial and appendicular growth plates during puberty remain unclear. In the present study, the strategy of ERß blocking resulted in increased longitudinal elongation of the appendicular bone (P < 0.01), whereas ERα blocking suppressed appendicular elongation (P < 0.05). Blocking both ERs did not have opposite effects on axial longitudinal growth. The expression of chondrocyte proliferation genes including collagen II, aggrecan, and Sox9 and hypertrophic marker genes including collagen X, MMP13, and Runx2 was significantly increased in the growth plate of female mice treated with ERß antagonist compared with that in the GP of control mice (P < 0.05). There were no significant differences in local insulin-like growth factor 1 (IGF-1) expression among these groups (P > 0.05), and Indian hedgehog protein (Ihh) and parathyroid-related protein (PTHrP) expressions differed among these groups (P < 0.05). ERs appeared not to affect axial bone growth during puberty in female mice (P > 0.05). Our data show that the blocking of different ER subtypes might have a region-specific influence on longitudinal appendicular and axial growth.
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Desenvolvimento Ósseo , Receptores de Estrogênio/metabolismo , Animais , Condrócitos/fisiologia , Feminino , Camundongos Endogâmicos C57BL , Piperidinas , Pirazóis , Pirimidinas , Distribuição Aleatória , Maturidade SexualRESUMO
Aviation medical research shows that disuse osteoporosis will occur after long-term space flight. Even with countermeasures such as exercise and drug treatments, this outcome cannot be avoided in flight. In recent years, the application of artificial gravity devices that change the mechanical microenvironment of bone in microgravity have shown promise in mitigating the risk of disuse osteoporosis. Considering the existence of osteocytes, a fluid-solid coupling finite element model for osteons with two-stage pore structure (Haversian canal, lacunar-canalicular system) was established. In order to study the changes in the mechanical behavior of osteocytes under the action of various artificial gravity (AG) devices, including long-arm centrifuge (LAC), short-arm centrifuge (SAC), and a lower body negative pressure (LBNP) chamber. In addition, the difference in pulsating pressure and static pressure stress caused by the gravity gradient under the AG devices was examined. The simulation results showed that the AG devices could effectively improve the stress level of osteocytes in microgravity. The mechanical microenvironment of osteocytes that was provided by the LAC was closest to that of the Earth's gravitational field. The mechanical stimulation on osteocytes was not significantly improved by the SAC, but from a practical viewpoint, it occupied less space than the LAC. The LBNP chamber created a higher level of stress for osteocytes. Therefore, the LAC was an ideal device for replacing Earth's gravitational field, except for the practical limitations of its physical size. In contrast, the LBNP device had the greatest application potential in training for its expansibility and convenience.
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Gravidade Alterada , Ausência de Peso , Simulação por Computador , Ósteon , OsteócitosRESUMO
In this work, combining first-principles calculations with kinetic Monte Carlo (KMC) simulations, we constructed an irregular carbon bridge on the graphene surface and explored the process of H migration from the Pt catalyst to carbon bridge, and further migration to the graphene surface. The calculated reaction diagrams show that the hydrogen atoms can easily migrate from the Pt cluster to the carbon bridge with a low barrier of 0.22-0.86 eV, and KMC simulations indicate that the migration reactions can take place at intermediate temperatures (91.9-329.5 K). Our research clarified the role of the carbon bridge: (1) the close combination of Pt clusters and carbon bridges reduces H2 adsorption enthalpy, which facilitates the spillover of H atoms from the Pt cluster to the carbon bridges and (2) the unsaturated carbon atoms on the carbon bridges have radical character and tend to bind radical H atoms. The subsequent study shows that the F atoms decorated on graphene can greatly reduce the migration barrier of H atoms from the carbon bridge to graphene. With F atoms decorated, the carbon atoms are in an electron-deficient state, which have a strong ability to bind the hydrogen atoms, and it promotes the migration of H atoms to the graphene surface. The migration barrier and reaction temperature are reduced to 0.72 eV and 279 K, respectively.
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The blood-spinal cord barrier (BSCB), a physical barrier between the blood and spinal cord parenchyma, prevents the toxins, blood cells, and pathogens from entering the spinal cord and maintains a tightly controlled chemical balance in the spinal environment, which is necessary for proper neural function. A BSCB disruption, however, plays an important role in primary and secondary injury processes related to spinal cord injury (SCI). After SCI, the structure of the BSCB is broken down, which leads directly to leakage of blood components. At the same time, the permeability of the BSCB is also increased. Repairing the disruption of the BSCB could alleviate the SCI pathology. We review the morphology and pathology of the BSCB and progression of therapeutic methods targeting BSCB in SCI.
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Barreira Hematoencefálica/metabolismo , Endotélio Vascular/metabolismo , Células-Tronco Neurais/metabolismo , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Animais , Barreira Hematoencefálica/patologia , Movimento Celular/fisiologia , Endotélio Vascular/patologia , Humanos , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapiaRESUMO
Cerebral ischemia-reperfusion injury (CIRI) is the observed continuation and deterioration of ischemic injury, and currently, there are no effective treatment strategies for the condition. It has been reported that microRNAs (miRNAs) serve an important role in CIRI by regulating pyroptosis. The present study demonstrated that miRNA-124 regulated CIRI by regulating STAT3. To explore the relationship between miRNA-124/STAT3 and pyroptosis in CIRI, CIRI was simulated using a middle cerebral artery occlusion model. Subsequently, miRNA-124 expression levels were altered via the intracerebroventricular injection of miRNA-124 agonist or antagonist. The degree of brain tissue injury was assessed by conducting TTC staining and neurological function scoring. Relative miRNA-124 expression levels were determined via reverse transcription-quantitative PCR. A luciferase reporter gene system verified the targeted binding of miRNA-124 to STAT3. The expression levels of key proteins and proinflammatory cytokines associated with pyroptosis [caspase-1, gasdermin D, interleukin (IL)-18 and IL-1ß] were detected via western blotting and immunohistochemistry. The increased expression levels of pyroptosis-associated proteins and proinflammatory cytokines in the I/R groups compared with the control group, indicated that pyroptosis intensified over time during CIRI, and miRNA-124 agonist significantly abrogated pyroptosis and improved neurological function compared with the control group. Furthermore, miRNA-124 inhibited STAT3 activation in a targeted manner, which also decreased the extent of pyroptosis. However, miRNA-124 antagonist reversed miR-124 agonist-mediated effects. Therefore, the present study indicated that miRNA-124 may provide neuroprotection against pyroptosis during CIRI, potentially via inhibition of the STAT3 signaling pathway.
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The study examines the association between exposure to sub-micrometric Particulate Matter (PM1) and allergic response in a group of sensitive young children (age: 2-10 years) from Ploiesti city, Romania. The city is the only urban agglomeration in Europe surrounded by four oil refineries. A panel study was conducted by collecting medical information from children with respiratory illnesses and atopy (n = 135). Hot Spot Analysis revealed the areas of the city that are susceptible to high levels of PM1. We found a close interaction between exposure to PM1 outdoor concentrations and various physiological changes and clinical symptoms in children including triggering of allergic reactions, rhinitis, alteration of lung function, upper and lower respiratory tract symptoms, and bronchial asthma. During the 2-year study period, the incidence of hospitalizations was 40.7%. Strong correlations (p < 0.001) were observed between the PM1 exposure and hospitalizations, and exposure and Immunoglobulin E (IgE). PM1 exposure was also correlated with eosinophils (p < 0.05). Another positive correlation was observed between hospitalizations and IgE levels (p < 0.05). The mean results of tested indicators were as follows: wheezing (5.3, 95% CI (1.4-1.8); Coeff. of var. (CV) = 30%), IgE (382, 95% CI (349-445); CV = 102%), and EO% (5.3, 95% CI (3.3-4.2); CV = 69.5%). We can conclude that exposure to PM1 influenced the frequency of wheezing episodes, increased hospitalizations, and the levels of allergic blood indicators in children, especially in infants and pre-schoolers. CAPSULE: Exposure to sub-micrometric particles (PM1) influences the frequency of wheezing episodes, hospitalizations, and the levels of allergic blood indicators in children, especially in infants and pre-schoolers.
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Hipersensibilidade , Material Particulado/efeitos adversos , Material Particulado/análise , Criança , Pré-Escolar , Cidades/epidemiologia , Europa (Continente) , Humanos , Lactente , Sons Respiratórios/etiologia , Romênia/epidemiologiaRESUMO
BACKGROUND: This study will investigate the clinical efficacy of Duyiwei capsule (DYWC) for the treatment of gingivitis. METHODS: Relevant studies will be searched in PUBMED, EMBASE, Cochrane Library, WANGFANG, VIP, CBM, and CNKI from inception to the March 31, 2020 without limitations of language and publication time. All potential randomized controlled trials on the clinical efficacy of DYWC for the treatment of gingivitis will be considered. Two authors will independently perform literature selection, data collection, and study quality assessment. Any disagreements will be solved by a third author through discussion. We will utilize RevMan 5.3 software for statistical analysis. RESULTS: This study will summarize present randomized controlled trials on the efficacy and safety of DYWC for the treatment of gingivitis. CONCLUSION: The findings of this study will provide evidence to show whether DYWC is effective and safety for gingivitis.Systematic review registration: INPLASY202040199.
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Gengivite/tratamento farmacológico , Gengivite/patologia , Medicina Tradicional Chinesa/métodos , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Resultado do Tratamento , Metanálise como AssuntoRESUMO
Effects of dietary supplemental stachyose on caecal skatole concentration, hepatic cytochrome P450 (CYP450, CYP) mRNA expressions and enzymatic activities in broilers were evaluated. Arbor Acre commercial mixed male and female chicks were assigned randomly into six treatments. The positive control (PC) diet was based on maize-soyabean meal, and the negative control (NC) diet was based on maize-non-soyabean meal. The NC diet was then supplemented with 4, 5, 6 and 7 g/kg stachyose to create experimental diets, named S-4, S-5, S-6 and S-7, respectively. Each diet was fed to six replicates of ten birds from days 1 to 49. On day 49, the caecal skatole concentrations in the PC, S-4, S-5, S-6 and S-7 groups were lower than those in the NC group by 42·28, 23·68, 46·09, 15·31 and 45·14 % (P < 0·01), respectively. The lowest pH value was observed in the S-5 group (P < 0·05). The stachyose-fed groups of broilers had higher caecal acetate and propionate levels compared with control groups, and propionate levels in the S-6 and S-7 groups were higher than those in the S-4 and S-5 groups (P < 0·001). The highest CYP3A4 expression was found in the S-7 group (P < 0·05), but this was not different from PC, S-4, S-5 and S-6 treatments. There was no significant difference in CYP450 (1A2, 2D6 and 3A4) enzymatic activities among the groups (P > 0·05). In conclusion, caecal skatole levels can be influenced by dietary stachyose levels, and 5 g/kg of stachyose in the diet was suggested.
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Ceco/química , Sistema Enzimático do Citocromo P-450/genética , Dieta/veterinária , Fígado/enzimologia , Oligossacarídeos/administração & dosagem , Escatol/análise , Acetatos/análise , Ração Animal , Animais , Galinhas/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Concentração de Íons de Hidrogênio , Masculino , Propionatos/análise , RNA Mensageiro/análise , Glycine max , Zea maysRESUMO
Species of the genus Retiboletus in China were investigated based on morphology and phylogenetic analysis of DNA sequences from the nuclear ribosomal large subunit (nrLSU) and the translation elongation factor 1-α gene (TEF1-α). Nine species were recovered from China, including two new and seven known species. The new species, namely Retiboletus ater and R. sinogriseus, from southwestern and northeastern China respectively, are documented and illustrated in this paper. Retiboletus ater is morphologically characterized by its black to grayish black pileus, white to grayish hymenophore, black to blackish stipe and white to grayish white context. Retiboletus sinogriseus is morphologically characterized by its brown to grayish-brown pileus, yellow to grayish-yellow hymenophore, pale yellow to brownish stipe and yellow to brownish-yellow context. Descriptions and line drawings of these two novel species and their comparisons with allied taxa are presented.