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1.
Spinal Cord ; 60(4): 332-338, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34628476

RESUMEN

STUDY DESIGN: Experimental animal study. OBJECTIVES: To assess the feasibility of a custom-designed parallel-moving (PM) clip, compared with a single-axle-lever (SAL) clip, for the development of a compressional spinal cord injury (SCI) model in rats. SETTING: Hospital laboratory in China. METHODS: We used a PM clip and a SAL clip with same compression rate, to develop a SCI model in rats, and set a sham group as a blank control. Within 3 weeks, each group of rats was evaluated for behavioral (Basso-Beattie-Bresnahan locomotor rating score, BBB), and electrophysiological changes (somatosensory evoked potential), and historical staining to observe the differences between the three groups. In particular, the mechanical results of the PM group were calculated. RESULTS: The BBB scores for the SAL and PM groups were significantly lower than those for the sham group (P < 0.05), no significant difference between the two methods (P > 0.05), but the values corresponding to the PM group had smaller standard deviations. The interpeak-latency (IPL) was significantly prolonged (P < 0.0001) and the peak-peak amplitude (PPA) was significantly reduced (P < 0.01) in SAL and PM groups than those in the sham group, but there was no statistical difference in both IPL and PPA between the two SCI groups (P > 0.05). Histological staining showed obvious pathological changes in two SCI groups, and the shape of the lesion zone in the PM group was more symmetrical than that in the SAL groups. CONCLUSIONS: The use of a compressional SCI model in rats with the PM clip we designed is an appropriate method to quantify the injury. The degree of the injury caused by this clip is more stable and uniform than those with classical methods.


Asunto(s)
Compresión de la Médula Espinal , Traumatismos de la Médula Espinal , Animales , Modelos Animales de Enfermedad , Potenciales Evocados Somatosensoriales , Humanos , Ratas , Ratas Sprague-Dawley , Médula Espinal/patología , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/patología , Traumatismos de la Médula Espinal/patología , Instrumentos Quirúrgicos
2.
Ecotoxicol Environ Saf ; 241: 113756, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35691196

RESUMEN

Zearalenone (ZEN) is a potent oestrogenic mycotoxin that is mainly produced by Fusarium species and is a serious environmental pollutant in animal feeds. Apiotrichum mycotoxinivorans has been widely used as a feed additive to detoxify ZEN. However, the effects of ZEN on A. mycotoxinivorans and its detoxification mechanisms remain unclear. In this study, transcriptomic and bioinformatic analyses were used to investigate the molecular responses of A. mycotoxinivorans to ZEN exposure and the genetic basis of ZEN detoxification. We detected 1424 significantly differentially expressed genes (DEGs), of which 446 were upregulated and 978 were downregulated. Functional and enrichment analyses showed that ZEN-induced genes were significantly associated with xenobiotic metabolism, oxidative stress response, and active transport systems. However, ZEN-inhibited genes were mainly related to cell division, cell cycle, and fungal development. Subsequently, bioinformatic analysis identified candidate ZEN-detoxification enzymes. The Baeyer-Villiger monooxygenases and carboxylesterases, which are responsible for the formation and subsequent hydrolysis of a new ZEN lactone, respectively, were significantly upregulated. In addition, the expression levels of genes related to conjugation and transport involved in the xenobiotic detoxification pathway were significantly upregulated. Moreover, the expression levels of genes encoding enzymatic antioxidants and those related to growth and apoptosis were significantly upregulated and downregulated, respectively, which made it possible for A. mycotoxinivorans to survive in a highly toxic environment and efficiently detoxify ZEN. This is the first systematic report of ZEN tolerance and detoxification in A. mycotoxinivorans. We identified the metabolic enzymes that were potentially involved in detoxifying ZEN in the GMU1709 strain and found that ZEN-induced transcriptional regulation of genes is key to withstanding highly toxic environments. Hence, our results provide valuable information for developing enzymatic detoxification systems or engineering this detoxification pathway in other species.


Asunto(s)
Zearalenona , Animales , Saccharomyces cerevisiae/metabolismo , Transcriptoma , Trichosporon , Xenobióticos , Zearalenona/toxicidad
3.
Angew Chem Int Ed Engl ; 61(35): e202205626, 2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-35672885

RESUMEN

Atomically precise copper clusters are highly desirable catalysts for electrocatalytic CO2 reduction reaction (CO2 RR) and provide an ideal platform for elaborating structure-activity relationships. However, systematic comparative studies of Cu cluster isomers for electrocatalytic CO2 RR are lacking because they are challenging to synthesize. A group of structurally precise Cu8 cluster isomers with different core structures (cube- and ditetrahedron-shaped) were developed and investigated for highly active and selective CO2 reduction. Electrocatalytic measurements showed that the ditetrahedron-shaped Cu8 cluster exhibited a higher FEHCOOH (≈92 %) at -1.0 V and higher selectivity than the cube-shaped cluster. Theoretical investigations revealed different levels of competitiveness with the hydrogen evolution reaction on the respective core-shaped Cu8 clusters and decreased free energies for the adsorbed HCOO* intermediates on the ditetrahedron-shaped Cu8 clusters.

4.
Metab Brain Dis ; 36(8): 2243-2253, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34529220

RESUMEN

Nociceptin opioid peptide (NOP) receptor modulates pain transmission and is considered a prospective target for pain management. Under acute pain conditions in rodents, however, no definitive conclusions about effects of systemically intervening NOP receptors on nociception, classical opioid-induced antinociception, tolerance and physical dependence have been drawn. Given that opioid analgesia has sex differences, and females experience greater pain and consume more opioids, clarifying these issues in females will help develop novel analgesics. To clarify the role of NOP receptors on the pharmacological profiles of µ-opioid receptor agonists, in this study, a selective agonist (SCH221510) and antagonist (SB612111) of the NOP receptor were subcutaneously administered in female mice in multiple animal models. In hot-plate test, neither SCH221510 (3 and 10 mg/kg, sc) nor SB612111 (10 mg/kg, sc) produced significant antinociception. SCH221510 (3 mg/kg, sc) attenuated but SB612111 (10 mg/kg, sc) enhanced morphine-induced antinociception, with rightward and leftward shift of morphine dose-response curves, respectively. SCH221510 (3 mg/kg, sc) combined with morphine (10 mg/kg, sc) accelerated the development of morphine antinociceptive tolerance. Conversely, SB612111 (10 mg/kg, sc) delayed morphine tolerance development. Neither SCH221510 (3 mg/kg, sc) nor SB612111 (10 mg/kg, sc) statistically significantly altered the development of morphine-induced physical dependence. Therefore, systemic activation of NOP receptors attenuated morphine antinociception to acute thermal stimuli, facilitated morphine-induced antinociceptive tolerance but did not robustly alter physical dependence in female mice. Systemic blockade of NOP receptors produced opposite actions. These findings demonstrate that N/OFQ-NOP receptor system plays diverse roles in modulating pharmacological profiles of µ-opioid receptor agonists.


Asunto(s)
Analgésicos Opioides , Morfina , Analgésicos Opioides/farmacología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Ratones , Morfina/farmacología , Péptidos Opioides/farmacología , Estudios Prospectivos , Receptores Opioides/agonistas , Nociceptina
5.
Prep Biochem Biotechnol ; 51(9): 860-870, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33439089

RESUMEN

Crude glycerol, a by-product of biodiesel production, was employed as the carbon source to produce lipase using Pichia pastoris. Under identical fermentation conditions, cell growth and lipase activity were improved using crude glycerol instead of pure glycerol. The impacts of crude glycerol impurities (methyl ester, grease, glycerol, methanol, and metal ions Na+, Ca2+, and Fe3+) on lipase production were investigated. Impurities accelerated P. pastoris entering the stationary phase. Na+, Ca2+, and grease in waste crude glycerol were the main factors influencing higher lipase activity. Through response surface optimization of Ca2+, Na+, and grease concentrations, lipase activity reached 1437 U/mL (15,977 U/mg), which was 2.5 times that of the control. This study highlights the economical and highly efficient valorization of crude glycerol, demonstrating its possible utilization as a carbon source to produce lipase by P. pastoris without pretreatment.


Asunto(s)
Medios de Cultivo/farmacología , Proteínas Fúngicas , Glicerol/farmacología , Lipasa , Rhizomucor/genética , Saccharomycetales/crecimiento & desarrollo , Medios de Cultivo/química , Proteínas Fúngicas/biosíntesis , Proteínas Fúngicas/genética , Glicerol/química , Lipasa/biosíntesis , Lipasa/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Rhizomucor/enzimología , Saccharomycetales/genética
6.
Echocardiography ; 37(10): 1627-1633, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32969521

RESUMEN

OBJECTIVE: This study sought to investigate the variation of right heart structure pre- and post-operation as risk factors for moderate to severe pulmonary regurgitation (PR) after repaired Tetralogy of Fallot and the best "cutoff" values for the transannular patch (TAP). METHODS: We collected surgical, echocardiographic, and computed tomographic data of Teralogy of Fallot (TOF) patients over two years and calculated z-score values based on the echocardiographic data. Based on the PR level after follow-up, the patients were divided into two groups, trivial to mild PR and moderate to severe PR. A multivariate logistic regression analysis was performed, and the receiver operating characteristic curve analysis was used to find the best "cutoff" value for risk factors. RESULTS: A total of 104 TOF patients were included in our cohort study. From the multivariate analysis, correction strategy (P = .002), difference in zRVOT (OR 1.974, 95% CI 1.354 to 2.878, P < .0001), and zPVA (OR 3.605, 95% CI 1.980 to 6.562, P < .0001) were the significant risk factors for moderate to severe PR. The "cutoff" value for the difference in zPVA that could predict moderate to severe PR in the TAP group was 3, and the optimal "cutoff" value for TAP was -1.4. CONCLUSIONS: The TAP is a risk factor for significant PR after surgery. We recommend the optimal "cutoff" value for TAP is -1.4 calculated using Shan-Shan Wang's data set. During the procedure, to limit the RVOT resection and restrict the enlargement of pulmonary annulus within a variation of z-score as 3 would reduce significant PR.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Insuficiencia de la Válvula Pulmonar , Válvula Pulmonar , Tetralogía de Fallot , Estudios de Cohortes , Humanos , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/cirugía , Insuficiencia de la Válvula Pulmonar/diagnóstico por imagen , Insuficiencia de la Válvula Pulmonar/etiología , Insuficiencia de la Válvula Pulmonar/cirugía , Estudios Retrospectivos , Tetralogía de Fallot/diagnóstico por imagen , Tetralogía de Fallot/cirugía , Resultado del Tratamiento
7.
ORL J Otorhinolaryngol Relat Spec ; 82(5): 257-267, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32726776

RESUMEN

OBJECTIVE: To investigate the expression of interleukin-17A (IL-17A) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and to analyze its effect on prognosis and to explore the role and mechanism of anti-IL-17A effect in vivo by establishing a murine nasal polyps (NP) model. METHODS: Patients with CRSwNP who underwent endoscopic sinus surgery and matched control subjects were collected. We investigated IL-17A expression in human NP tissues using immunohistochemistry and analyzed their clinical features, including Lund-Mackay computed tomography scoring (LMCS) before surgery, Lund-Kennedy endoscopic scoring (LKES) before surgery (LKES B), LKES 6 months after surgery (LKES A), and reduction of LKES (LKES R). Then, after establishing the murine NP model to detect the expression and correlation of IL-17A and matrix metalloproteinase-9 (MMP-9) in nasal tissue, we studied nasal lavage fluid and serum by PCR and enzyme-linked immunosorbent assay in vivo. Anti-IL-17A treatment was administered in the murine NP model to confirm the function of IL-17A during the pathogenic processes. RESULTS: IL-17A expression was upregulated in NP tissues from patients with CRSwNP compared with control subjects (p < 0.001). The number of IL-17A+ cells was significantly negatively correlated with LKES R in patients with CRSwNP (p < 0.01). However, there was no significant correlation between IL-17A and LMCS or LKES B (all p < 0.05). Further, IL-17A and MMP-9 were more abundant in nasal mucosa of the murine NP model compared with that of control mice (all p < 0.05), and severe polypoid lesions were apparently observed in murine NP models. Anti-IL-17A treatment downregulated the mRNA and protein expression of MMP-9 in nasal mucosa and reduced the number of polypoid lesions in the murine NP model (all p < 0.05). CONCLUSION: Our results suggest that IL-17A plays a crucial role and may affect the prognosis of CRSwNP. Anti-IL-17A treatment may reduce the formation of polypoid lesions through inhibition of MMP-9 expression.


Asunto(s)
Pólipos Nasales , Rinitis , Sinusitis , Animales , Enfermedad Crónica , Humanos , Interleucina-17 , Ratones , Pólipos Nasales/complicaciones , Pronóstico , Rinitis/complicaciones , Sinusitis/complicaciones
8.
Biochem Biophys Res Commun ; 512(3): 460-466, 2019 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-30902386

RESUMEN

Morphine is a potent opioid analgesic used to alleviate moderate or severe pain, but the development of drug tolerance and dependence limits its use in pain management. Our previous studies showed that the candidate protein for I1 imidazoline receptor, imidazoline receptor antisera-selected (IRAS)/Nischarin, interacts with µ opioid receptor (MOR) and modulates its trafficking. However, there is no report of the effect of IRAS on morphine tolerance and physical dependence. In the present study, we found that IRAS knockout (KO) mice showed exacerbated analgesic tolerance and physical dependence compared to wild-type (WT) mice by chronic morphine treatment. Chronic morphine treatment down-regulated the expression of MOR in spinal cord of IRAS KO mice, while had no significant effect on MOR expression in WT mice. We observed the compensatory increase of cAMP accumulation in spinal cord after morphine tolerance, and this change was more significant in KO mice than WT mice. Furthermore, KO mice showed more elevation in the phosphorylation of AMPA receptor GluR1-S845 than WT mice, while the total expression of GluR1 remained unchanged after morphine dependence. Altogether, these data suggest that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo through modulating MOR expression, as well as AMPA GluR1-S845 phosphorylation, which might be one of the mechanisms underlying the development of opiate addiction.


Asunto(s)
Analgésicos Opioides/farmacología , Tolerancia a Medicamentos , Receptores de Imidazolina/metabolismo , Dependencia de Morfina/metabolismo , Morfina/farmacología , Animales , AMP Cíclico/metabolismo , Receptores de Imidazolina/genética , Ratones , Ratones Noqueados , Dependencia de Morfina/genética
9.
Metab Brain Dis ; 34(5): 1421-1430, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31313126

RESUMEN

The precise contributions of ventral tegmental area (VTA) dopaminergic (DAergic) neurons to reward-related behaviors are a longstanding hot topic of debate. Whether the activity of VTA DAergic neurons directly modulates rewarding behaviors remains uncertain. In the present study, we investigated the fundamental role of VTA DAergic neurons in reward-related movement and reinforcement by employing dopamine transporter (DAT)-Cre transgenic mice expressing hM3Dq, hM4Di or channelrhodopsin 2 (ChR2) in VTA DAergic neurons through Cre-inducible adeno-associated viral vector transfection. On the one hand, locomotion was tested in an open field to examine motor activity when VTA DAergic neurons were stimulated or inhibited by injection of the hM3Dq or hM4Di ligand clozapine-N-oxide (CNO), respectively. CNO injection to selectively activate or inhibit VTA DAergic neurons significantly increased or decreased locomotor activity, respectively, compared with vehicle injection, indicating that VTA DAergic neuron stimulation is directly involved in the regulation of motor activity. On the other hand, we used the optical intracranial self-stimulation (oICSS) model to investigate the causal link between reinforcement and VTA DAergic neurons. Active poking behavior but not inactive poking behavior was significantly escalated in a frequency- and pulse duration-dependent manner. In addition, microdialysis revealed that the concentration of dopamine (DA) in the nucleus accumbens (NAc) was enhanced by selective optogenetic activation of VTA DAergic neurons. Furthermore, systemic administration of a DA D1 receptor antagonist significantly decreased oICSS reinforcement. Our research profoundly demonstrates a direct regulatory role of VTA DAergic neurons in movement and reinforcement and provides meaningful guidance for the development of novel treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.


Asunto(s)
Neuronas Dopaminérgicas/metabolismo , Actividad Motora/fisiología , Área Tegmental Ventral/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Clozapina/análogos & derivados , Clozapina/farmacología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Ratones , Ratones Transgénicos , Actividad Motora/efectos de los fármacos , Optogenética , Recompensa , Autoestimulación , Área Tegmental Ventral/efectos de los fármacos
10.
Metab Brain Dis ; 34(4): 1029-1041, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31152340

RESUMEN

Increasing evidence indicates that excessive drug consumption is sufficient for the transition from recreational and controlled drug use to uncontrolled use and addiction. However, the underlying mechanisms are debated. Some neurobehavioral and neuroimaging evidence indicates that dorsolateral striatum (dlStr)-dependent habit learning plays a key role in excessive drug intake and the transition to addiction, but little is known about the molecular events. The present study investigated whether dlStr miR-134, an important regulator of synaptic transmission and plasticity, is involved in excessive methamphetamine intake. We established excessive and uncontrolled methamphetamine self-administration model in rats by permitting animals extended access to drug (6 h/session/d, LgA group), whereas animals that were limited to access to drug (2 h/session/d, ShA group) exhibited low and controlled self-administration. miR-134 expression in dlStr was significantly increased and its target LIMK1 expression was decreased in the LgA group, but not in the ShA group, compared with the saline control group. However, passive methamphetamine exposure did not alter miR-134 and LIMK1 levels in dlStr. We also found that down-regulation of miR-134 in dlStr through local microinjection of a lentivirus carrying miR-134 sponge (LV-miR-134-Sil) significantly reduced methamphetamine infusions and excessive consumption in LgA group, rather than ShA group. These results indicated that dlStr miR-134, perhaps via its target LIMK1, contributed to excessive and uncontrolled methamphetamine intake, supporting the hypothesis that stimulus-response habit formation is an important mechanism underlying the transition from controlled drug use to uncontrolled drug use and addiction.


Asunto(s)
Conducta Adictiva/metabolismo , Estimulantes del Sistema Nervioso Central/administración & dosificación , Cuerpo Estriado/metabolismo , Metanfetamina/administración & dosificación , MicroARNs/metabolismo , Animales , Cuerpo Estriado/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , MicroARNs/genética , Ratas , Ratas Sprague-Dawley , Autoadministración
11.
Eur Arch Otorhinolaryngol ; 276(5): 1397-1403, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30788581

RESUMEN

PURPOSE: Budesonide improves the prognosis of chronic rhinosinusitis (CRS). However, few reports have examined whether its use for nasal irrigation, compared to normal saline, improves the prognosis of patients after endoscopic sinus surgery (ESS). We compared the effects of nasal irrigation with budesonide and normal saline in CRS patients after ESS. METHODS: Sixty CRS patients who had undergone ESS were randomly divided into an experimental group (30 patients), which used budesonide nasal irrigation, and a control group (30 patients), which used normal saline nasal irrigation. All patients received regular follow-up evaluations and were assessed via questionnaires, including the Lund-Kennedy endoscopic score (LKES), the symptom visual analog scale (VAS), the 22-item Sino-Nasal Outcome Test (SNOT-22), the Short-Form 36-Item Questionnaire (SF-36), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS) and a side effects scale. RESULTS: Scores of polyposis, mucosal edema, secretions and total score of LKES; VAS scores of nasal blockage, hyposmia and rhinorrhea; and SNOT-22 results in both groups were significantly improved 3 months after ESS. Scores of polyposis, mucosal edema, secretions and scarring and total score of LKES in experimental group were significantly better than in control group 3 months after ESS. No significant differences were observed in SF-36, SAS or SDS before or 3 months after ESS within or between the two groups. The side effects of the two groups were not significantly different. CONCLUSIONS: Nasal irrigation improved the prognosis of CRS patients after ESS. Budesonide nasal irrigation had a better effect than normal saline nasal irrigation.


Asunto(s)
Budesonida/administración & dosificación , Endoscopía , Lavado Nasal (Proceso)/métodos , Obstrucción Nasal , Senos Paranasales , Rinitis , Sinusitis , Adulto , Antiinflamatorios/administración & dosificación , Enfermedad Crónica , Endoscopía/efectos adversos , Endoscopía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obstrucción Nasal/diagnóstico , Obstrucción Nasal/etiología , Obstrucción Nasal/prevención & control , Senos Paranasales/diagnóstico por imagen , Senos Paranasales/efectos de los fármacos , Senos Paranasales/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/prevención & control , Pronóstico , Rinitis/diagnóstico , Rinitis/cirugía , Sinusitis/diagnóstico , Sinusitis/cirugía , Resultado del Tratamiento
13.
Metab Brain Dis ; 33(5): 1721-1731, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30019267

RESUMEN

Previous studies have shown that agmatine, a potential neuromodulator or co-transmitter, exhibited antidepressant-like action in animal models, yet its mechanism, especially the receptor mechanism, remains unclear. In the present study, using efaroxan, a preferential antagonist of I1 imidazoline receptor (I1R) and yohimbine, an antagonist of α2 adrenergic receptor (α2AR), we investigated the roles of I1R and α2AR in agmatine's antidepressant-like effect in acute and sub-acute depression models in mice. We found that in the tail-suspension test (TST) and the forced swimming test (FST), acute administration of agmatine (20 and 40 mg/kg, p.o.) significantly shortened the immobility time. Concurrent administration of efaroxan (1 mg/kg, i.p.) completely abolished the antidepressant-like effects of agmatine (40 mg/kg, p.o.) whereas yohimbine (5 mg/kg, i.p.) failed to exert similar effects, suggesting that the acute antidepressant-like effects of agmatine was mainly mediated by I1R but not α2AR. Additionally, in the learned helplessness (LH) test, repeated administration of agmatine (20 mg/kg, p.o., q.d.) for 5 days significantly decreased the escape latency and the number of escape failure, and these effects were respectively abolished by concurrent administration of efaroxan (0.5 mg/kg,i.p., q.d.) and yohimbine (3 mg/kg, i.p., q.d.) for 5 days, suggesting that the antidepressant-like action of agmatine in the LH test was achieved via the activation of both I1R and α2AR. In summary, we found that the antidepressant-like effects of agmatine in the TST and the FST were mediated by activating I1R and in the sub-acute LH test were mediated by activating both I1R and α2AR.


Asunto(s)
Agmatina/uso terapéutico , Antidepresivos/uso terapéutico , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Actividad Motora/efectos de los fármacos , Antagonistas Adrenérgicos alfa/farmacología , Agmatina/farmacología , Animales , Antidepresivos/farmacología , Benzofuranos/farmacología , Modelos Animales de Enfermedad , Suspensión Trasera , Imidazoles/farmacología , Receptores de Imidazolina/antagonistas & inhibidores , Masculino , Ratones , Natación , Yohimbina/farmacología
14.
Drug Dev Ind Pharm ; 43(2): 190-203, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27599027

RESUMEN

The interaction between copovidone and Carbopol 907 is pH dependent. When the pH of an aqueous solution fell below pH 4.5, a water-insoluble complex began to form and precipitate. This complex resulted from a hydrogen-bond-induced interaction between the carboxylic groups in Carbopol 907 and the carbonyl groups of N-vinylpyrrolidone repeat units in copovidone. Consisting of these two polymers at an approximate 1:1 weight ratio, the complex was an amorphous material with a glass transition temperature of 157 °C. The interpolymer complexation in situ was applied to modify drug release properties of Carbopol 907-based theophylline matrix tablets. The effect of copovidone on drug release was dependent on the pH of the dissolution medium. In a 0.1 N hydrochloride acid solution at pH 1.2 and 50 mM acetate buffer at pH 4.0, an insoluble tablet matrix was formed as a result of the in situ interpolymer complexation, and theophylline was released therefore via Fickian diffusion. In a 50 mM phosphate buffer at pH 6.8, drug release from the matrix tablets was still impacted by the in situ interpolymer complexation because of the low-pH microenvironment induced by Carbopol 907. As a result, drug release rate of the matrix tablet containing both polymers at pH 6.8 was slower than that of the matrix tablets containing individual polymers. We observed similar drug release rates at both pH 1.2 and pH 6.8 between tablets containing the physical blend of these two polymers and tablets containing preformed interpolymer complexes.


Asunto(s)
Resinas Acrílicas/química , Preparaciones de Acción Retardada/química , Pirrolidinas/química , Comprimidos/química , Teofilina/química , Compuestos de Vinilo/química , Preparaciones de Acción Retardada/farmacocinética , Liberación de Fármacos , Excipientes/química , Concentración de Iones de Hidrógeno , Cinética , Pirrolidinonas , Solubilidad
15.
Yi Chuan ; 39(5): 423-429, 2017 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-28487274

RESUMEN

The ABO blood type is one of the most common and widely used genetic traits in humans. Three glycosyltransferase-encoding gene alleles, IA, IB and i, produce three red blood cell surface antigens, by which the ABO blood type is classified. By using the ABO blood type experiment as an ideal case for genetics teaching, we can easily introduce to the students several genetic concepts, including multiple alleles, gene interaction, single nucleotide polymorphism (SNP) and gene evolution. Herein we have innovated and integrated our ABO blood type genetics experiments. First, in the section of Molecular Genetics, a new method of ABO blood genotyping was established: specific primers based on SNP sites were designed to distinguish three alleles through quantitative real-time PCR. Next, the experimental teaching method of Gene Evolution was innovated in the Population Genetics section: a gene-evolution software was developed to simulate the evolutionary tendency of the ABO genotype encoding alleles under diverse conditions. Our reform aims to extend the contents of genetics experiments, to provide additional teaching approaches, and to improve the learning efficiency of our students eventually.


Asunto(s)
Sistema del Grupo Sanguíneo ABO/genética , Técnicas de Genotipaje/métodos , Alelos , Cartilla de ADN/genética , Genética de Población/métodos , Genotipo , Humanos , Polimorfismo de Nucleótido Simple/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estudiantes
16.
Chem Rec ; 16(3): 1531-48, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27218806

RESUMEN

Much progress has been made in the field of research on organic near-infrared materials for potential applications in photonics, communications, energy, and biophotonics. This account mainly describes our research work on organic near-infrared materials; in particular, donor-acceptor small molecules, organometallics, and donor-acceptor polymers with the bandgaps less than 1.2 eV. The molecular designs, structure-property relationships, unique near-infrared absorption, emission and color/wavelength-changing properties, and some emerging applications are discussed.

17.
J Neuroinflammation ; 11: 112, 2014 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-24946684

RESUMEN

BACKGROUND: Inflammation plays a key role in the pathophysiology of ischemic stroke. Some proinflammatory mediators, such as cytokines and chemokines, are produced in stroke. Chemokine-like factor 1 (CKLF1), as a novel C-C chemokine, displays chemotactic activities in a wide spectrum of leukocytes and plays an important role in brain development. In previous studies, we have found that the expression of CKLF1 increased in rats after focal cerebral ischemia and treatment with the CKLF1 antagonist C19 peptide decreased the infarct size and water content. However, the role of CKLF1 in stroke is still unclear. The objective of the present study was to ascertain the possible roles and mechanism of CKLF1 in ischemic brain injury by applying anti-CKLF1 antibody. METHODS: Male Sprague-Dawley rats were subjected to one-hour middle cerebral artery occlusion. Antibody to CKLF1 was applied to the right cerebral ventricle immediately after reperfusion; infarct volume and neurological score were measured at 24 and 72 hours after cerebral ischemia. RT-PCR, Western blotting and ELISA were utilized to characterize the expression of adhesion molecules, inflammatory factors and MAPK signal pathways. Immunohistochemical staining and myeloperoxidase activity was used to determine the extent of neutrophil infiltration. RESULTS: Treatment with anti-CKLF1 antibody significantly decreased neurological score and infarct volume in a dose-dependent manner at 24 and 72 hours after cerebral ischemia. Administration with anti-CKLF1 antibody lowered the level of inflammatory factors TNF-α, IL-1ß, MIP-2 and IL-8, the expression of adhesion molecules ICAM-1 and VCAM-1 in a dose-dependent manner. The results of immunohistochemical staining and detection of MPO activity indicated that anti-CKLF1 antibody inhibited neutrophil infiltration. Further studies suggested MAPK pathways associated with neutrophil infiltration in cerebral ischemia. CONCLUSIONS: Selective inhibition of CKLF1 activity significantly protects against ischemia/reperfusion injury by decreasing production of inflammatory mediators and expression of adhesion molecules, thereby reducing neutrophils recruitment to the ischemic area, possibly via inhibiting MAPK pathways. Therefore, CKLF1 may be a novel target for the treatment of stroke.


Asunto(s)
Anticuerpos/uso terapéutico , Quimiocinas/inmunología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Proteínas con Dominio MARVEL/inmunología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Infarto Encefálico/etiología , Infarto Encefálico/prevención & control , Quimiocinas/antagonistas & inhibidores , Citocinas/metabolismo , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/complicaciones , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Proteínas con Dominio MARVEL/antagonistas & inhibidores , Masculino , Examen Neurológico , Infiltración Neutrófila/fisiología , Péptidos/uso terapéutico , Ratas , Ratas Sprague-Dawley , Estadísticas no Paramétricas , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo
18.
Exp Mol Pathol ; 97(2): 266-72, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25036405

RESUMEN

This study aims to evaluate the genetic basis and activity of lecithin cholesterol acyltransferase (LCAT) in a novel Mongolian gerbil model for hyperlipidemia. Gerbils may be susceptible to high fat and cholesterol (HF/HC) diets, which can rapidly lead to the development of hyperlipidemia. Approximately 10-30% of gerbils that are over 8months old and fed controlled diets spontaneously develop hyperlipidemia. Using the HF/HC diet model, we detected triglycerides (TG), total cholesterol (TC), HDL (high density lipoprotein)-C, LDL (low density lipoprotein)-C and LCAT in both old (>8months) and young gerbils. The TC and HDL-C levels were two times higher in old gerbils compared with young gerbils (P<0.01). However, in the old group the LCAT activity fell slightly compared with the normal lipidemia group. It is reasonable to hypothesize that this may be associated with single nucleotide polymorphisms of the LCAT gene. We cloned this gene to investigate the sensitivity of the gerbil to the HF/HC diet and spontaneous hyperlipidemia. The entire LCAT gene was cloned by splicing sequences of RACE (rapid amplification of cDNA ends) and nest-PCR products (AN: KC533867.1). The results showed that the 3683base pair gene consists of six exons and five introns. The LCAT protein consists of 444 amino acid (AA) residues, which are analogous to the human LCAT gene, and includes 24 signal peptide AA and 420 mature protein AA. Expression of LCAT was detected in the kidney, spleen and adrenal tissue, apart from the liver, by immunohistochemistry. The abundance of the protein was greater in the older group compared with the control group. Polymorphisms were analyzed by PCR-SSCP (PCR-single-strand conformation polymorphism) but none were found in 444 animals of the ZCLA closed population (a Chinese cultured laboratory gerbil population).


Asunto(s)
Hiperlipidemias/genética , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Polimorfismo de Nucleótido Simple , Animales , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Exones , Gerbillinae , Hiperlipidemias/etiología , Hiperlipidemias/metabolismo , Intrones , Masculino , Especificidad de Órganos , Fosfatidilcolina-Esterol O-Aciltransferasa/química , Fosfatidilcolina-Esterol O-Aciltransferasa/metabolismo
19.
Macromol Rapid Commun ; 35(18): 1592-7, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25078781

RESUMEN

A series of fluorene-based conjugated polymers containing the aggregation-induced emissive (AIE)-active tetraphenylethene and dicarboxylate pseudocrown as a receptor exhibits a unique dual-mode sensing ability for selective detection of lead ion in water. Fluorescence turn-off and turn-on detections are realized in 80%-90% and 20% water in tetrahydrofuran (THF), respectively, for lead ion with a concentration as low as 10(-8) m.


Asunto(s)
Fluorescencia , Plomo/análisis , Polímeros/química , Espectrometría de Fluorescencia/métodos , Contaminantes Químicos del Agua/análisis , Furanos/química , Iones/análisis , Iones/química , Plomo/química , Espectroscopía de Resonancia Magnética , Modelos Químicos , Estructura Molecular , Reproducibilidad de los Resultados , Contaminantes Químicos del Agua/química
20.
World J Surg Oncol ; 12: 1, 2014 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-24387189

RESUMEN

BACKGROUND: Pelvic reconstruction after hemipelvectomy can greatly improve the weight-bearing stability of the supporting skeleton and improve patients' quality of life. Although an autograft can be used to reconstruct pelvic defects, the most suitable choice of autograft, i.e., the use of either femur or tibia, has not been determined. We aimed to analyze the mechanical stresses of a pelvic ring reconstructed using femur or tibia after hemipelvectomy using finite element (FE) analysis. METHODS: FE models of normal and reconstructed pelvis were established based on computed tomography images, and the stress distributions were analyzed under physiological loading from 0 to 500 N in both intact and restored pelvic models using femur or tibia. RESULTS: The vertical displacement of the intact pelvis was less than that of reconstructed pelvis, but there was no significant difference between the two reconstructed models. In FE analysis, the stress distribution of the intact pelvic model was bilaterally symmetric and the maximum stresses were located at the sacroiliac joint, arcuate line, ischiatic ramus, and ischial tuberosity. The maximum stress in each part of the reconstructed pelvis greatly exceeded that of the intact model. The maximum von Mises stress of the femur was 13.9 MPa, and that of the tibia was 6.41 MPa. However, the stress distribution was different in the two types of reconstructed pelvises. The tibial reconstruction model induced concentrated stress on the tibia shaft making it more vulnerable to fracture. The maximum stress on the femur was concentrated on the connections between the femur and the screws. CONCLUSIONS: From a biomechanical point of view, the reconstruction of hemipelvic defects with femur is a better choice.


Asunto(s)
Fémur/cirugía , Procedimientos Ortopédicos , Huesos Pélvicos/cirugía , Procedimientos de Cirugía Plástica , Prótesis e Implantes , Tibia/cirugía , Anciano , Femenino , Análisis de Elementos Finitos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estrés Mecánico , Trasplante Autólogo , Soporte de Peso/fisiología
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