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Boron is especially required for the growth of meristem and reproductive organs, but the molecular mechanisms underlying the preferential distribution of B to these developing tissues are poorly understood. Here, we show evidence that a member of nodulin 26-like intrinsic protein (NIP), OsNIP3;1, is involved in this preferential distribution in rice (Oryza sativa). OsNIP3;1 was highly expressed in the nodes and its expression was up-regulated by B deficiency, but down-regulated by high B. OsNIP3;1 was polarly localized at the xylem parenchyma cells of enlarged vascular bundles of nodes facing toward the xylem vessels. Furthermore, this protein was rapidly degraded within a few hours in response to high B. Knockout of this gene hardly affected the uptake and root-to-shoot translocation of B, but altered B distribution in different organs in the above-ground parts, decreased distribution of B to the new leaves, and increased distribution to the old leaves. These results indicate that OsNIP3;1 located in the nodes is involved in the preferential distribution of B to the developing tissues by unloading B from the xylem in rice and that it is regulated at both transcriptional and protein level in response to external B level.
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Boro/metabolismo , Proteínas de la Membrana/metabolismo , Oryza/genética , Proteínas de Plantas/metabolismo , Transporte Biológico , Proteínas de la Membrana/genética , Meristema/citología , Meristema/genética , Meristema/metabolismo , Oryza/citología , Oryza/metabolismo , Hojas de la Planta/citología , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Xilema/citología , Xilema/genética , Xilema/metabolismoRESUMEN
Terpene lactones are a class of bioactive constituents of standardized preparations of Ginkgo biloba leaf extract, extensively used as add-on therapies in patients with ischemic cardiovascular and cerebrovascular diseases. This investigation evaluated human pharmacokinetics of ginkgo terpene lactones and impact of their carboxylation in blood. Human subjects received oral YinXing-TongZhi tablet or intravenous ShuXueNing, two standardized ginkgo preparations. Their plasma protein-binding and platelet-activating factor antagonistic activity were assessed in vitro. Their carboxylation was assessed in phosphate-buffered saline (pH 7.4) and in human plasma. After dosing YinXing-TongZhi tablet, ginkgolides A and B and bilobalide exhibited significantly higher systemic exposure levels than ginkgolides C and J; after dosing ShuXueNing, ginkgolides A, B, C, and J exhibited high exposure levels. The compounds' unbound fractions in plasma were 45-92%. Apparent oral bioavailability of ginkgolides A and B was mostly >100%, while that of ginkgolides C and J was 6-15%. Bilobalide's bioavailability was probably high but lower than that of ginkgolides A/B. Terminal half-lives of ginkgolides A, B, and C (4-7 h) after dosing ShuXueNing were shorter than their respective values (6-13 h) after dosing YinXing-TongZhi tablet. Half-life of bilobalide after dosing the tablet was around 5 h. Terpene lactones were roughly evenly distributed in various body fluids and tissues; glomerular-filtration-based renal excretion was the predominant elimination route for the ginkgolides and a major route for bilobalide. Terpene lactones circulated as trilactones and monocarboxylates. Carboxylation reduced platelet-activating factor antagonistic activity of ginkgolides A, B, and C. Ginkgolide J, bilobalide, and ginkgo flavonoids exhibited no such bioactivity. Collectively, differences in terpene lactones' exposure between the two preparations and influence of their carboxylation in blood should be considered in investigating the relative contributions of terpene lactones to ginkgo preparations' therapeutic effects. The results here will inform rational clinical use of ginkgo preparations.
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Medicamentos Herbarios Chinos/farmacocinética , Ginkgólidos/farmacocinética , Lactonas/farmacocinética , Factor de Activación Plaquetaria/antagonistas & inhibidores , Adulto , Animales , Fenómenos Bioquímicos/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Femenino , Ginkgo biloba/química , Ginkgólidos/sangre , Ginkgólidos/química , Ginkgólidos/orina , Células HEK293 , Humanos , Lactonas/sangre , Lactonas/química , Lactonas/orina , Masculino , Conejos , Adulto JovenRESUMEN
pH variation could cause a stress response in euryhaline penaeids, we evaluated the mortality, growth performance, osmoregulation gene expression, digestive enzyme activity, histology, and resistance against Vibrio parahemolyticus of white shrimp Litopenaeus vannamei reared under conditions of gradual changes to a low-pH environment (gradual-low pH, 6.65-8.20) or a high-pH environment (gradual-high pH, 8.20-9.81) versus a normal pH environment (8.14-8.31) during a 28-d experiment. Consequently, under gradual-high pH, the cumulative mortality rate (CMR) rose with time until 39.9% on days 28; the weight gain percentage (WGP) and length gain percentage (LGP) decreased continuously. However, under gradual-low pH, the CMR of shrimp stabilized at 6.67% during 7-28 d; the WGP and LGP decreased first and then returned to normal. These results indicated that L. vannamei displayed a moderate tolerance to gradual-low pH, compared with gradual-high pH. Under gradual-low pH, the Na+/K+-ATPase, cytoplasmic carbonic anydrase (CAc), and glycosyl-phosphatidylinositol-linked carbonic anhydrase (CAg) transcripts of shrimp increased continuously or then back to normal; the amylase, lipase, and trypsin activities decreased first and then returned to normal or increased; the hepatopancreases and midguts showed histopathological lesions first and then got remission. Thus, the major adaptation mechanism of shrimp to gradual-low pH might be its high osmoregulation ability, which made shrimp achieve a new, balanced steady-state, then promoted longer intestinal villi and recuperative hepatopancreases of shrimp with enhanced digestive enzyme activities to increase nutrient absorption after long-term exposure. Meanwhile, the enhanced resistance against V. parahemolyticus under gradual-low pH would probably inhibit disease outbreak in the shrimp farming.
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Aclimatación/fisiología , Penaeidae/crecimiento & desarrollo , Aclimatación/genética , Animales , Anhidrasas Carbónicas/metabolismo , China , Explotaciones Pesqueras , Expresión Génica , Hepatopáncreas/enzimología , Concentración de Iones de Hidrógeno , Osmorregulación/genética , Penaeidae/genética , Penaeidae/microbiología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Vibrio parahaemolyticus/patogenicidadRESUMEN
Evidence was controversial about whether nerve stimulation (NS) can optimize ultrasound guidance (US)-guided nerve blockade for peripheral nerve block. This review aims to explore the effects of the two combined techniques. We searched EMBASE (from 1974 to March 2015), PubMed (from 1966 to Mar 2015), Medline (from 1966 to Mar 2015), the Cochrane Central Register of Controlled Trials and clinicaltrials.gov. Finally, 15 randomized trials were included into analysis involving 1,019 lower limb and 696 upper limb surgery cases. Meta-analysis indicated that, compared with US alone, USNS combination had favorable effects on overall block success rate (risk ratio [RR] 1.17; confidence interval [CI] 1.05 to 1.30, P = 0.004), sensory block success rate (RR 1.56; CI 1.29 to 1.89, P < 0.00001), and block onset time (mean difference [MD] -3.84; CI -5.59 to -2.08, P < 0.0001). USNS guidance had a longer procedure time in both upper and lower limb nerve block (MD 1.67; CI 1.32 to 2.02, P < 0.00001; MD 1.17; CI 0.95 to 1.39, P < 0.00001) and more patients with anesthesia supplementation (RR 2.5; CI 1.02 to 6.13, P = 0.05). USNS guidance trends to result in a shorter block onset time than US alone as well as higher block success rate, but no statistical difference was demonstrated, as more data are required. © 2017 IUBMB Life, 69(9):720-734, 2017.
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Bloqueo Nervioso/métodos , Dolor/tratamiento farmacológico , Nervios Periféricos/efectos de los fármacos , Ultrasonografía/métodos , Anestesia/métodos , Anestésicos/uso terapéutico , Humanos , Extremidad Inferior/inervación , Extremidad Inferior/cirugía , Dolor/fisiopatología , Nervios Periféricos/fisiopatología , Nervios Periféricos/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Extremidad Superior/inervación , Extremidad Superior/cirugíaRESUMEN
AIM: Tanshinol is an important catechol in the antianginal herb Salvia miltiorrhiza roots (Danshen). This study aimed to characterize tanshinol methylation. METHODS: Metabolites of tanshinol were analyzed by liquid chromatography/mass spectrometry. Metabolism was assessed in vitro with rat and human enzymes. The major metabolites were synthesized for studying their interactions with drug metabolizing enzymes and transporters and their vasodilatory properties. Dose-related tanshinol methylation and its influences on tanshinol pharmacokinetics were also studied in rats. RESULTS: Methylation, preferentially in the 3-hydroxyl group, was the major metabolic pathway of tanshinol. In rats, tanshinol also underwent considerable 3-O-sulfation, which appeared to be poor in human liver. These metabolites were mainly eliminated via renal excretion, which involved tubular secretion mainly by organic anion transporter (OAT) 1. The methylated metabolites had no vasodilatory activity. Entacapone-impaired methylation did not considerably increase systemic exposure to tanshinol in rats. The saturation of tanshinol methylation in rat liver could be predicted from the Michaelis constant of tanshinol for catechol-O-methyltransferase (COMT). Tanshinol had low affinity for human COMT and OATs; its methylated metabolites also had low affinity for the transporters. Tanshinol and its major human metabolite (3-O-methyltanshinol) exhibited negligible inhibitory activities against human cytochrome P450 enzymes, organic anion transporting polypeptides 1B1/1B3, multidrug resistance protein 1, multidrug resistance-associated protein 2, and breast cancer resistance protein. CONCLUSION: Tanshinol is mainly metabolized via methylation. Tanshinol and its major human metabolite have low potential for pharmacokinetic interactions with synthetic antianginal agents. This study will help define the risk of hyperhomocysteinemia related to tanshinol methylation.
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Ácidos Cafeicos/farmacocinética , Fármacos Cardiovasculares/farmacocinética , Medicamentos Herbarios Chinos/farmacocinética , Hígado/enzimología , Salvia miltiorrhiza/química , Administración Oral , Animales , Biotransformación , Ácidos Cafeicos/administración & dosificación , Ácidos Cafeicos/aislamiento & purificación , Ácidos Cafeicos/toxicidad , Fármacos Cardiovasculares/administración & dosificación , Fármacos Cardiovasculares/aislamiento & purificación , Fármacos Cardiovasculares/toxicidad , Catecol O-Metiltransferasa/metabolismo , Cromatografía Liquida , Sistema Enzimático del Citocromo P-450/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/toxicidad , Interacciones de Hierba-Droga , Humanos , Inyecciones Intravenosas , Túbulos Renales/metabolismo , Masculino , Espectrometría de Masas , Proteínas de Transporte de Membrana/metabolismo , Metilación , Microsomas Hepáticos/enzimología , Proteína 1 de Transporte de Anión Orgánico/metabolismo , Fitoterapia , Raíces de Plantas , Plantas Medicinales , Ratas Sprague-Dawley , Eliminación Renal , Sulfatos/metabolismoRESUMEN
Mesenchymal stem cells derived from adipose tissue have the capacity to differentiate into endodermal, mesoderm and ectodermal cell lineages in vitro, which are an ideal engraft in tissue-engineered repair. In this study, mouse adipose-derived stem cells (ADSCs) were isolated from subcutaneous fat. The markers of ADSCs, CD13, CD29, CD44, CD71, CD73, CD90, CD105, CD166, Nestin, GFAP and MAP-2 were detected by immunofluorescence assays. The ADSCs were cultured in cocktail factors (including ATRA, GGF-2, bFGF, PDGF and forskolin) for neurogenic differentiation. The neurogenic cells markers, Nestin, GFAP and MAP-2 were analyzed using immunofluorescence and real-time PCR after dramatic changes in morphology. Neurogenic cells from ADSCs were autologous transplanted into the mouse of spinal cord injury for observation neurogenic cells colonization in spinal cord. The result demonstrated that the mouse ADSCs were positive for the CD13, CD29, CD44, CD71, CD73, CD90, CD105 and CD166 but negative for neurogenic cell markers, MAP-2, GFAP and Nestin. After neurogenic differentiation, the neurogenic cells were positive for neurogenic cell special markers, gene expression level showed a time-lapse increase, and the cells were successful colonized into spinal cord. In conclusion, our research shows that a population of neuronal cells can be specifically generated from ADSCs and that induced cells may allow for participation in tissue-repair.
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Adipocitos/citología , Células-Madre Neurales/citología , Células-Madre Neurales/trasplante , Neurogénesis , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/terapia , Adipocitos/metabolismo , Animales , Diferenciación Celular , Supervivencia Celular , Células Cultivadas , Ratones , Regeneración Nerviosa , Células-Madre Neurales/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Trasplante Autólogo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the efficacy and clinical results of total internal protection technique in anterior cruciate ligament reconstruction. METHODS: A total of 56 patients undergoing anterior cruciate ligament reconstruction treated from January 2018 to December 2019 were selected. According to the different surgical methods, they were divided into total internal reconstruction group and standard bone tunnel group. There were 21 patients in the total internal reconstruction group, including 15 males and 6 females, aged from 20 to 48 with an average of (35.6±6.7) years old, and 35 patients in the standard tibial tunnel group, including 26 males and 9 females, aged 22 to 51 years old with an average of (33.7±9.6) years old. Preoperative examination of Lachman test was positive, magnetic resonance indicated anterior cruciate ligament rupture. There were no significant differences between the two groups in age, sex, body mass index, time from injury to ACL reconstruction, combined meniscus injury and operation method, operation time, ligament diameter, ligament length and other general information. Postoperative evaluation included operation duration, length and diameter of transplanted tendon after braid. International Knee Documentation Committee (IKDC) score, Lysholm score, Tegner score and perioperative complications 2 years after surgery. RESULTS: Both groups were followed up, ranging from 24 to 30 months with an average of (26.9±3.4) months. Postoperative incision healing was good, and no failure or joint infection occurred at the last follow-up. There was no statistically significant difference between the two groups in IKDC score, Lysholm score and Tegner score before, 1 year and 2 years after surgery. However, IKDC score, Lysholm score and Tegner score at 1 year and 2 years after surgery. CONCLUSION: The same postoperative function and stability of knee joint can be obtained by both the residual whole technique and the standardized reconstruction technique. In the residual whole group, only the semitendinosus muscle is taken, and the femoral thin muscle is retained, with greater tibial bone mass preserved, which is safe and effective in clinical practice.
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Lesiones del Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Masculino , Femenino , Humanos , Adulto , Adulto Joven , Persona de Mediana Edad , Ligamento Cruzado Anterior/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Artroscopía/métodos , Articulación de la Rodilla/cirugía , Lesiones del Ligamento Cruzado Anterior/cirugíaRESUMEN
OBJECTIVE: To explore the clinical efficacy of double beam double tunnel enhanced reconstruction technique in the treatment of knee anterior cruciate ligament(ACL) training injuries. METHODS: Twenty-nine cases of ACL injury of knee joint from January 2021 to December 2021 were retrospectively analyzed. All the cases were underwent ligament reconstruction surgery. Cases were grouped by surgical technique:there were 14 patients in conventional reconstruction group, including 13 males and 1 female, aged from 22 to 31 years old with an average of (27.07±7.28) years old, autogenous hamstring tendon was used for ligament reconstruction. There were 15 patients in the enhanced reconstruction group, including 13 males and 2 females, aged from 25 to 34 years old with an average of (29.06±4.23) years old, double tunnel ligament reconstruction, the autogenous hamstring muscle was used as the anteromedial bundle, and the posterolateral bundle was replaced by a high-strength line. The difference between knee tibial anterior distance, Lysholm score, International Knee Literature Committee (IKDC) subjective score, Tegner motor level score and visual analog scale (VAS) at 6th and 12th months after the surgery, limb symmetry index (LSI) were recorded at the last follow-up and surgery-related adverse effects during follow-up. RESULTS: All patients were followed up, ranged from 13 to 15 months with an average of (13.7±0.8) months. There were no serious adverse reactions related to surgery during the period. There was no statistical difference between the preoperative general data and the observation index of the two groups (P>0.05). The difference in tibial anterior distance at 6 and 12 months in the enhanced reconstruction group (1.45±0.62) mm and (1.74±0.78) mm which were lower those that in the conventional reconstruction group (2.42±0.60) mm and (2.51±0.63) mm(P<0.05). There was no significant difference in postoperative Lysholm score, Tegner motor level score, IKDC score, VAS, and limb symmetry index at the last follow-up(P>0.05). CONCLUSION: The enhanced reconstruction technique can more effectively maintain the stability of the knee joint and has no significant effect on the postoperative knee joint function compared with the traditional ligament reconstruction technique. The short-term curative effect is satisfactory, and it is suitable for the group with high sports demand.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Humanos , Masculino , Femenino , Adulto , Reconstrucción del Ligamento Cruzado Anterior/métodos , Lesiones del Ligamento Cruzado Anterior/cirugía , Adulto Joven , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Water ecological restoration zoning, which involves articulating goals for restoring water ecosystems upwards and guiding the spatial layout of restoration projects downwards, is key to achieving systematic restoration of water resource elements. There are many challenges in water ecological restoration zoning, including disparate hierarchical systems, incomplete indicators, and vague boundaries. With Guangxi Hechi, a karst ecologically fragile region, as a case, we developed a multidimensional zoning system framework based on "watershed natural unit-dominant ecological function-ecological stress risk". The first-level zoning employed river systems and geomorphic types as indicators and delineated the sub-watershed unit as the boundary. The second-level zoning adopted a "top-down" division method to clarify the goal of water ecological restoration based on watershed natural geography and select three indicators (water conservation, biodiversity, and landscape cultural services) for evaluation. We used the K-means clustering method to identify dominant ecological functions in spatial units, with the sub-watershed unit demarcating second-level zoning boundaries. The third-level zoning was the specific implementation unit for ecological restoration projects. We used three indicators (soil erosion, flooding risk, and human interference) to characterize water ecosystem risk from external coercion, and defined the third-level zoning. We delineated 11 primary water ecological zones, four secondary zones, and three tertiary zones. Synthesizing tertiary zoning results accounted for spatial differentiation characteristics of watershed natural geography, dominant ecological functions, and ecological coercion risks, and combining sub-watershed and township administrative units determined zoning boundaries, water ecological restoration zoning was comprehensively classified into five categories and 32 sub-ecological zones. Corresponding ecological restoration strategies were proposed based on zoning and classification.
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Conservación de los Recursos Hídricos , Ecosistema , Ríos , China , Conservación de los Recursos Hídricos/métodos , Conservación de los Recursos Naturales/métodos , Restauración y Remediación Ambiental/métodos , Ecología , Monitoreo del Ambiente/métodosRESUMEN
AIM: Both Borneolum (Chinese name Bingpian; dextrorotatory borneol) and Borneolum syntheticum (synthetic Bingpian; a mixture of optically inactive borneol and isoborneol) have been used for medicinal purposes in Chinese traditional medicine. The aim of this study was to develop a sensitive assay for measuring volatile ingredients borneol, isoborneol, and their metabolite camphor in pharmacokinetic study of Bingpian. METHODS: Rat plasma samples were prepared using liquid-liquid microextraction: 70 µL of plasma sample (containing 125 nmol/L naphthalene as the internal standard) was extracted with 35 µL of n-hexane. The resulting n-hexane extract (20 µL) was introduced into a gas chromatography/mass spectrometry system using programmable temperature vaporizing-based large-volume injection. The assay was validated to demonstrate its reliability for the intended use. Using this assay, pharmacokinetic studies of Bingpian, synthetic Bingpian, and Fufang-Danshen tablets (containing synthetic Bingpian) were conducted in rats. RESULTS: The extraction efficiency for the analytes and the internal standard from plasma was almost constant with decrease in n-hexane-to-plasma volume ratio, thus enabling a small volume of extracting solvent to be used for sample preparation, and enhancing the assay sensitivity. The lower quantification limit for measuring borneol, isoborneol, and camphor in plasma was 0.98 nmol/L, which was 33-330 times more sensitive than those reported earlier for Bingpian and synthetic Bingpian. The applicability of the miniaturized liquid-liquid extraction technique could be extended to measure other volatile and nonvolatile medicinal compounds in biomatrices, which can be predicted according to the analytes' octanol/water distribution coefficient (logD) and acid dissociation constant (pKa). CONCLUSION: This assay is sensitive, accurate and free of matrix effects, and can be applied to pharmacokinetic studies of Bingpian, synthetic Bingpian, and Bingpian-containing herbal products.
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Canfanos/farmacocinética , Alcanfor/farmacocinética , Cromatografía de Gases y Espectrometría de Masas/métodos , Animales , Medicamentos Herbarios Chinos/farmacocinética , Límite de Detección , Microextracción en Fase Líquida , Masculino , Ratas , Ratas Sprague-Dawley , Sensibilidad y Especificidad , Solventes/química , ComprimidosRESUMEN
We focus on the fixed-time convergence and robustness of gradient-based dynamic networks for solving convex optimization. Most of the existing gradient-based dynamic networks with fixed-time convergence have limited ability to resist interferences of noises. To improve the convergence of the gradient-based dynamic networks, we design a new activation function and propose a gradient-based dynamic network with fixed-time convergence. The proposed dynamic network has a smaller upper bound of the convergence time than the existing dynamic networks with fixed-time convergence. A time-varying scaling parameter is employed to speed up the convergence. Our gradient-based dynamic network is proved to be robust against bounded noises and is able to resist the interference of unbounded noises. The numerical tests illustrate the effectiveness and superiority of the proposed network.
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Redes Neurales de la ComputaciónRESUMEN
Ischemic stroke is the most common cerebrovascular disease, and vascular obstruction is an important cause of this disease. As the main method for the management of carotid artery stenosis, carotid endarterectomy (CEA) is an effective and preventive treatment measure in ischemic cerebrovascular disease. This study aims to propose the application of a new enhanced recovery after surgery (ERAS) nutritional support regimen in CEA, which can significantly improve the perioperative nutritional status of patients. A total of 74 patients who underwent CEA were included and randomly divided into two groups: 39 patients received nutritional therapy with the ERAS protocol (ERAS group) and 35 patients received routine perioperative nutritional support (control group). Our results showed that the levels of major clinical and biochemical parameters (albumin, hemoglobin, creatinine, calcium and magnesium levels, etc.) in the ERAS group were significantly higher than those in the control group after surgery (p < 0.05). Additionally, patients in the ERAS group had dramatically shorter postoperative length of stay and reflected higher mean satisfaction at discharge (p < 0.001). Moreover, no statistically significant differences were observed in postoperative complication rates and Mini-mental State Examination scores at discharge. The emergence of this neurosurgical ERAS nutritional support program can effectively intervene in perioperative nutritional status, and notably reduce postoperative hospital stays.
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OBJECTIVE: To explore the effects of propofol on the PI3K/Akt signaling pathway and the endoplasmic reticulum stress pathway of apoptosis induced by ischemia-reperfusion in isolated rat hearts. METHODS: Forty isolated rat hearts were completely randomly assigned into 5 different groups: control (C), ischemia/reperfusion (I/R), propofol (P), propofol plus Wortmannin (P + Wort) and Wortmannin (W). The isolated hearts were perfused on a Langendorff apparatus. Except for group C, all hearts were subjected to 30 min global ischemia and 120 min reperfusion. In the P, P + W and W groups, 50 µmol/L propofol or 50 µmol/L propofol + 100 nmol/L Wortmannin or 100 nmol/L Wortmannin were respectively added in the K-H buffer to perfuse for 10 min at pre-ischemia and 20 min at the beginning of reperfusion. The parameters of cardiac function were recorded at pre-ischemia and at the 120 min of reperfusion. The apoptotic index was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (Tunel). The expressions of caspase-12 and CCAAT/C/EBP homologous protein (chop) were measured by immunohistochemistry while those of Akt and p-Akt (Ser473) detected by Western blot. RESULTS: Compared with the I/R group, LVEDP significantly deceased and +dp/dtmax significantly increased, the apoptotic index [(27.89 ± 1.04)% vs (33.70 ± 2.20)%], the expressions of caspase-12 [(0.1728 ± 0.0096) vs (0.2332 ± 0.0114)] and chop [(0.1889 ± 0.0078) vs (0.2407 ± 0.0123)] significantly deceased while that of p-Akt (Ser473) significantly increased in Group P (P < 0.05). Wortmannin abolished the partial protective effects of propofol postconditioning (P < 0.05). CONCLUSION: Propofol perfusion may attenuate the endoplasmic reticulum stress pathway of apoptosis induced by ischemia/reperfusion in isolated rat hearts partly through the PI3K/Akt signal pathway.
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Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Propofol/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Corazón/efectos de los fármacos , Técnicas In Vitro , Masculino , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Ischemic stroke is one of the leading causes of mortality worldwide. The available treatments are not effective. Phosphodiesterase 9A (PDE9A) is an intracellular cyclic guanosine monophosphate (cGMP) hydrolase considered to be a promising therapeutic target for brain diseases. This study explored neuroprotective effects and the underlying mechanism of LW33, a novel PDE9A inhibitor, on ischemic stroke in vitro and in vivo. METHODS: A middle cerebral artery occlusion (MCAO) model was established in adult male Sprague-Dawley rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) model was established in human SH-SY5Y cells to mimic ischemia-reperfusion injury in vitro. RESULTS: LW33 increased cell viability, reduced lactate dehydrogenase activity, and OGD/R-induced apoptosis of SH-SY5Y cells. The protective effects of LW33 against stroke occurred in the recovery phase. LW33 administration significantly reduced cerebral infarction volume in MCAO rats, without causing significant deformation or necrosis of neurons in the cortex. LW33 also improved learning and cognitive dysfunction and reduced other pathological changes in MCAO rats in the recovery period. Moreover, LW33 stimulated the cGMP/PKG/CREB pathway and up-regulated the expression of the apoptosis-related proteins, and this effect was reversed by KT5823 treatment. CONCLUSION: LW33 inhibited cell apoptosis and promoted neuronal repair to alleviate OGD/R and MCAO induced pathological alterations via the cGMP/PKG/CREB pathway, indicating that LW33 may be a promising therapeutic target for ischemic stroke.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Fármacos Neuroprotectores , Daño por Reperfusión , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevención & control , GMP Cíclico , Glucosa/farmacología , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Oxígeno/metabolismo , Inhibidores de Fosfodiesterasa/farmacología , Hidrolasas Diéster Fosfóricas/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Transducción de SeñalRESUMEN
We consider the problem of minimizing the sum of an average of a large number of smooth convex component functions and a possibly nonsmooth convex function that admits a simple proximal mapping. This class of problems arises frequently in machine learning, known as regularized empirical risk minimization (ERM). In this article, we propose mSRGTR-BB, a minibatch proximal stochastic recursive gradient algorithm, which employs a trust-region-like scheme to select stepsizes that are automatically computed by the Barzilai-Borwein method. We prove that mSRGTR-BB converges linearly in expectation for strongly and nonstrongly convex objective functions. With proper parameters, mSRGTR-BB enjoys a faster convergence rate than the state-of-the-art minibatch proximal variant of the semistochastic gradient method (mS2GD). Numerical experiments on standard data sets show that the performance of mSRGTR-BB is comparable to and sometimes even better than mS2GD with best-tuned stepsizes and is superior to some modern proximal stochastic gradient methods.
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OBJECTIVE: To observe the clinical efficacy of allogeneic peripheral blood stem cell transplantationï¼allo-HSCTï¼ on the treatment of adult acute leukemia patients, moreover, to establish and evaluate a Logistic model to predict the risk of relapse in adult acute leukemia patients after allo-HSCT. METHODS: The clinical data of 145 adult acute leukemia patients treated by peripheral blood stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 was enrolled and analyzed retrospectively. Complications and survival of patients were observed. The relationship between patients' age, diagnosis, leukocyte count at onset, risk stratification, time of diagnosis to transplantation, HCT-CI, minimal residual disease pre-transplantation, donor-recipient sex relationship, HLA match degree, prophylaxis of graft versus host disease(GVHD), donor age, number of transfused mononuclear cells, CD34 positive cells, engraftment time, acute and chronic GVHD, CMV, EBV infection, and hemorrhagic cystitis and recurrence after transplantation were analyzed by logistic regression. Relapse prediction model was established and evaluated according to the results. RESULTS: Among 145 acute leukemia patients, 81 with acute myeloid leukemia, 64 with acute lymphocytic leukemia, 18 with EBV infection, 2 with post-transplant lymphoproliferative disorder(PTLD), 85 with CMV, 26 with hemorrhagic cystitis, 65 patients developed acute GVHD, 51 patients developed chronic GVHD and 45 patients relapsed. The overall survival ï¼OSï¼ rates in one and three years were 86.4% and 61.8%, and the progress-free survival ï¼PFSï¼ rates in one and three years were 67.5% and 62.4%, respectively. There were significant differences in OS and PFS between relapsed and non-relapsed patients, as well as AML and ALL patients. Univariate analysis revealed that patient's age, risk stratification, time to transplantation, HCT-CI index, ATG based GVHD prophylaxis, minimal residual disease pre-transplantation, GVHD prophylaxis, and acute and chronic GVHD were associated with the relapse of disease, multivariate logistic regression analysis showed that pre-transplantation minimal residual disease showed positively correlation with relapse of the disease, while chronic GVHD showed negatively correlation. CONCLUSION: The relapse rate of adult acute leukemia patients treated with allo-HSCT in our hospital is 31.0%, and OS of AML patients is better than ALL patients'. OS of relapsed patients is significantly lower than non-relapsed patients'. Pre-transplantation minimal residual disease is a risk factor of relapse. The risk of relapse is reduced in patients with chronic GVHD.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trasplante de Células Madre de Sangre Periférica , Adulto , Humanos , Leucemia Mieloide Aguda/terapia , Recurrencia , Estudios Retrospectivos , Acondicionamiento PretrasplanteRESUMEN
As a flavonoid, rutin has been found to have a wide range of biological functions, such as resisting inflammation and oxidation, and preventing cerebral hemorrhage and hypertension. It has been found to play an important role in osteoporosis and other orthopedic diseases in recent years. MC3T3-E1 cells were randomly divided into a control group, a rutin-1 group (0.01 mmol/L), a rutin-2 group (0.05 mmol/L) and a rutin-3 group (0.1 mmol/L). Osteogenic differentiation of cells was induced by osteogenic induction fluid. The control group was treated with the maximum dose of drug solvent. 2~3 days later, the solvent was replaced with fresh osteogenic induction fluid containing rutin. After a certain period of routine culture, the cells were collected for subsequent experiments. The expression of Runx2 gene in cells in all groups was detected by Real-time PCR; the expression of Runx2 protein was detected by Western blot and immunocytochemistry; the activity of ALP was detected by reagent kit method; osteogenic differentiation was analyzed by alizarin red staining. The results of Real-time PCR showed that, compared with the control group, the treatment of cells with rutin can significantly increase the expression of Runx2 gene (p<0.05); the higher the concentration, the higher the expression of Runx2 gene, and significant differences were found among groups in which different concentrations were used (p<0.05); the results of Western blot and IHC showed that the expression trend of Runx2 protein in each group was consistent with PCR results. In drug treatment groups, the activity of ALP was significantly higher than that in the control group (p<0.05); there were significant differences among groups in which different concentrations were used (p<0.05). The results of alizarin red staining showed that calcified nodules were formed in all groups and that the area of calcified nodules formed in groups treated with rutin was greater than that in the control group; the greater the concentration, the larger the area. Rutin can promote osteoblastic differentiation; and the greater the concentration, the more effective it is.
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Fosfatasa Alcalina/metabolismo , Diferenciación Celular/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Osteoblastos/efectos de los fármacos , Rutina/farmacología , Animales , Línea Celular Tumoral , RatonesRESUMEN
Dimethylated sulfur compounds play an important role in global sulfur cycle. We investigated the seasonality of dimethylsulfoniopropionate (DMSP), dimethylsulfoxide (DMSO), dimethylsulfide (DMS) and associated processes in two north China marginal seas during 2014 and 2016. High concentrations of DMS, DMSP and DMSO occurred in summer/spring, while the lowest were observed in winter. This clear seasonality was primarily driven by biomass abundance and phytoplankton communities, reflected in chlorophyll a concentrations and the composition/ratios of diatoms and dinoflagellates. The spring maximum was attributed to the annual occurrence of algal bloom. The sea-to-air fluxes of DMS also varied largely between seasons, with an average of 8.84, 11.87, 10.50 and 2.14 µmol m-2 day-1 in spring, summer, autumn and winter, respectively. Given the seasonal uncertainty of sea-to-air flux, the seasonality or situations where specific blooms occur regularly should be considered for accurate estimation of annual global DMS emission.
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Agua de Mar , Compuestos de Azufre , China , Clorofila A , Océanos y Mares , Fitoplancton , Estaciones del AñoRESUMEN
From August 1990 to December 2007, 156 patients with humeral shaft nonunion were treated with our patented Ni-Ti shape memory alloy swan-like memory pressure connector (SMC). The SMC device cooled with ice before implantation was warmed to 40-50 degrees C after implantation to produce balanced axial and compression forces to stabilise the fracture three-dimensionally. This combined with autologous bone grafting achieved bone tissue regeneration in the fracture and promoted smooth recovery of joint function, with a nonunion healing rate of 98.7% after a single SMC implantation. Failure of nonunion healing occurred in only two cases but was successfully managed by a further operation. Complications were not found in any of these patients apart from four with pre-existing radial nerve injuries. These results demonstrate the effectiveness of the SMC device for the management of humeral shaft nonunion. The device provides continuous compression of the fracture with minimal trauma to the local blood supply.