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PURPOSE: Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods. METHODS: This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Non-normally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher's exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. RESULTS: A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time (p < 0.001), less blood loss (p < 0.001), better hematoma evacuation (p = 0.003), and a shorter stay in the intensive care unit (p = 0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group (p = 0.014). CONCLUSIONS: Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.
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Polygala tenuifolia Wild is an ancient traditional Chinese medicine. Its main component, tenuifolin (TEN), has been proven to improve cognitive impairment caused by neurodegenerative diseases and ovariectomy. However, there was hardly any pharmacological research about TEN and its potential gender differences. Considering the reduction of TEN on learning and memory dysfunction in ovariectomized animals, therefore, we focused on the impact of TEN in different mice genders in the current study. Spontaneous alternation behavior (SAB), light-dark discrimination, and Morris water maze (MWM) tests were used to evaluate the mice's learning and memory abilities. The field excitatory postsynaptic potential (fEPSP) of the hippocampal CA1 region was recorded using an electrophysiological method, and the morphology of the dendritic structure was examined using Golgi staining. In the behavioral experiments, TEN improved the correct rate in female mice in the SAB test, the correct rate in the light-dark discrimination test, and the number of crossing platforms in the MWM test. Additionally, TEN reduced the latency of female mice rather than male mice in light-dark discrimination and MWM tests. Moreover, TEN could significantly increase the slope of fEPSP in hippocampal Schaffer-CA1 and enhance the total length and the number of intersections of dendrites in the hippocampal CA1 area in female mice but not in male mice. Collectively, the results of the current study showed that TEN improved learning and memory by regulating long-term potentiation (LTP) and dendritic structure of hippocampal CA1 area in female mice but not in males. These findings would help to explore the improvement mechanism of TEN on cognition and expand the knowledge of the potential therapeutic value of TEN in the treatment of cognitive impairment.
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Región CA1 Hipocampal , Dendritas , Diterpenos de Tipo Kaurano , Potenciación a Largo Plazo , Animales , Femenino , Masculino , Región CA1 Hipocampal/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Potenciación a Largo Plazo/fisiología , Ratones , Dendritas/efectos de los fármacos , Memoria/efectos de los fármacos , Factores Sexuales , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiologíaRESUMEN
Ischemic stroke is a neurological disease that leads to brain damage and severe cognitive impairment. In this study, extracellular vesicles(Ev) derived from mouse hippocampal cells (HT22) were used as carriers, and adenosine (Ad) was encapsulated to construct Ev-Ad to target the damaged hippocampus. The results showed that, Ev-Ad had significant antioxidant effect and inhibited apoptosis. In vivo, Ev-Ad reduced cell death and reversed inflammation in hippocampus of ischemic mice, and improved long-term memory and learning impairment by regulating the expression of the A1 receptor and the A2A receptor in the CA1 region. Thus, the developmental approach based on natural carriers that encapsulating Ad not only successfully restored nerves after ischemic stroke, but also improved cognitive impairment in the later stage of ischemic stroke convalescence. The development and design of therapeutic drugs provides a new concept and method for the treatment of cognitive impairment in the convalescent phase after ischemic stroke.
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Vesículas Extracelulares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Ratones , Adenosina/farmacología , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismo , Hipocampo , Vesículas Extracelulares/metabolismo , Cognición , Accidente Cerebrovascular Isquémico/metabolismoRESUMEN
Objective@#To construct a prediction model for preeclampsia (PE) risk in twin-pregnant women, so as to provide the basis for early screening and prevention of PE.@*Methods@#A total of 467 twin-pregnant women who underwent prenatal examination and delivered at Huzhou Maternal and Child Health Hospital were selected. Sixty cases with preeclampsia (PE) were included in the case group, and 60 women without PE were included in the control group. General information, blood biochemical indicators and uterine artery resistance index (UtA-RI) were collected. A logistic regression model was used to screen predictive factors and establish a nomogram. The Bootstrap method was performed for the internal validation; the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively.@*Results@#In the case group, there were 47 individuals (78.33%) aged younger than 35 years, 21 individuals (35.00%) with pre-pregnancy body mass index (BMI) of 25 kg/m2 and above, and 33 individuals (55.00%) with in vitro fertilization. In the control group, there were 57 individuals (95.00%) aged younger than 35 years, 8 individuals (13.33%) with pre-pregnancy BMI of 25 kg/m2 and above, and 39 individuals (65.00%) with natural pregnancy. Multivariable logistic regression analysis identified age, pre-pregnancy BMI, method of conception, placental growth factor (PLGF) and UtA-RI as risk prediction factors for PE in twin-pregnant women. The established nomogram had an area under the ROC curve of 0.827 (95%CI: 0.755-0.899), a sensitivity of 0.767, a specificity of 0.733, a good discrimination and calibration, and a relatively high clinical net benefit.@*Conclusion@#The nomogram established by age, pre-pregnancy BMI, method of conception, PLGF and UtA-RI has a good predictive value for the risk of PE in twin-pregnant women.
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BACKGROUND: Parkinson's disease (PD), the most common neurodegenerative disorder, primarily affects dopaminergic neurons in the substantia nigra (SN). In addition to severe motor dysfunction, PD patients appear apparent cognitive impairments in the late stage. Cognitive dysfunction is accompanied by synaptic transmission damage in the hippocampus. Cordycepin has been reported to alleviate cognitive impairments in neurodegenerative diseases. PURPOSE: The study aimed to estimate the protection roles of cordycepin on cognitive dysfunction in PD model and explore the potential mechanisms. METHODS: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the PD model in vivo and in vitro experiments. In the in vivo experiments, the C57BL / 6 mice were intraperitoneally injected with MPTP and intragastric administration with cordycepin. Open field test (OFT) was used to estimate the exercise ability. Spontaneous alternation behavioral (SAB) and morris water maze (MWM) tests were used to evaluate the learning and memory abilities. The hippocampal slices from C57BL / 6 and Kunming mice in the in vitro experiments were used to record field excitatory postsynaptic potential (fEPSP) by electrophysiological methods. Western blotting was used to examine the level of tyrosine hydroxylase (TH) in the in vivo experiments and the levels of adenosine A1 and A2A receptors (A1R and A2AR) in the in vitro experiments, respectively. The drugs of MPTP, cordycepin, DPCPX and SCH58261 were perfused through dissolving in artificial cerebrospinal fluid. RESULTS: Cordycepin could significantly reduce the impairments on motor, exploration, spatial learning and memory induce by MPTP. MPTP reduced the amplitude of LTP in hippocampal CA1 area but cordycepin could improve LTP amplitudes. Cordycepin at dosage of 20 mg/kg also increased the TH level in SN. In the in vitro experiments, MPTP inhibited synaptic transmission in hippocampal Schaffer-CA1 pathway with a dose-dependent relationship, while cordycepin could reverse the inhibition of synaptic transmission. Furthermore, the roles of cordycepin on synaptic transmission could been attenuated in the presence of the antagonists of A1R and A2AR, DPCPX and SCH58261, respectively. Interestingly, the level of A2AR rather than A1R in hippocampus was significantly decreased in the cordycepin group as compared to the control. CONCLUSION: The present study has showed that cordycepin could improve cognitive function in the PD model induced by MPTP through regulating the adenosine A2A receptors. These findings were helpful to provide a new strategy for the dementia caused by Parkinson's disease.
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Enfermedad de Parkinson , Animales , Ratones , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Adenosina , Cognición , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Enfermedad de Parkinson/tratamiento farmacológicoRESUMEN
AIMS: To determine the effect of design thinking approach in interprofessional education programme of human sexuality course. DESIGN: A pre-test and post-test of single-group quasi-experimental study. METHODS: The 35 nursing students and seven psychology students in their third year were selected by the computer randomly sampling through the lottery method. The course proceeded between September 2019 and January 2020. The participants had received an 8-week, 16-hr design thinking approach in interprofessional education programme of human sexuality course (one section per week, 2 hr per section). We used the nursing attitude toward sexual healthcare scale, nursing intervention toward sexual healthcare scale to assess students' attitude and behaviour intention toward sexual health care and competence of interprofessional education scale to assess students' competence of cooperation before and after the teaching programme. Data analysis used descriptive statistics and t-tests. A qualitative reflection log was also provided and analysed for themes. The SQUIRE-EDU checklist was followed. RESULTS: The students' attitude and behavioural intention dimension score in the post-test is higher than those in the pre-test and reach statistically significant differences both in total and subscale. Interprofessional core competence score of Observation Experience, Reflective Feedback, Interprofessional Cooperation, Innovative Design, and Applied Technology score in the post-test is higher than those in the pre-test and reach statistically significant differences both in total and subscale. Design thinking in interprofessional education programme of human sexuality course could significantly improve both nursing and psychology students' attitude, behaviour intention of providing sexual health care and competence of interprofessional cooperation.
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Educación Interprofesional , Estudiantes de Enfermería , Humanos , Proyectos de Investigación , Actitud del Personal de Salud , Estudiantes de Enfermería/psicología , SexualidadRESUMEN
Polysaccharide of Balanophora involucrata Hook. f. (BPS), the major component of Balanophora involucrata Hook. f., was confirmed the protective effect on liver injury in our previous study. This research aimed to investigate the protective mechanism of BPS on experimental liver injury by attenuating cell ferroptosis through modulating solute carrier family 7 member 11/glutathione peroxidase 4 (SLC7A11/GPX4) pathway. The animal experiment was approved by the Experimental Animal Ethical Committee of Hubei Minzu University and all rats had received human care in compliance with the institutional animal care guidelines. Rats were given intraperitoneal injection of (D-galactosamine, D-GalN) solution (800 mg·kg-1) one time to establish the acute liver injury model. The results showed aspartate amino transferase (AST), alanine aminotransferase (ALT) and 4-hydroxynonenal (4-HNE) levels in serum were decreased, and the contents of reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA) and lipid peroxide (LPO) in liver tissues also decreased and glutathione (GSH) level increased after BPS administration with 200 mg·kg-1. Besides, BPS reduced iron deposition and increased the expression of SLC7A11 and GPX4 proteins in liver tissue. In conclusion, BPS ameliorated experimental liver injury by alleviating cell ferroptosis through SLC7A11/GPX4 pathway. The present study pointed to the possibility of utilizing BPS for protection against liver injury in clinic.
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INTRODUCTION: Slow colon transit and visceral hypersensitivity are recognized as major pathophysiological mechanisms in irritable bowel syndrome with constipation (IBS-C). However, there is a lack of therapies targeting both abdominal pain and colonic motility. This study was designed to investigate the long-term effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) in patients with IBS-C. METHODS: Fifty-two patients with IBS-C were randomized into 2 groups: daily TEA for 4 weeks (n = 26) and daily sham-TEA for 4 weeks (n = 26). The number of complete spontaneous bowel movements per week (CSBMs/week, primary outcome), Irritable Bowel Syndrome Severity Scoring System, Patient Assessment of Constipation Quality of Life, visual analog scale (VAS) pain score, colonic transit time, and anorectal physiology were evaluated before treatment and at the end of the treatment. Colonic transit was assessed with radiopaque markers. Electrocardiograms were recorded for assessing autonomic functions. RESULTS: (i) TEA improved constipation and abdominal pain. After the treatment, the number of CSBMs/week during the last week in the TEA group was higher than that in the sham-TEA group (3.5 ± 1.6 vs 2.3 ± 0.6, P = 0.002). Similar effects were also noted in the visual analog scale pain score ( P = 0.002) and Irritable Bowel Syndrome Severity Scoring System score ( P = 0.025). In addition, there was a significant improvement in the quality of life of patients with constipation. The Patient Assessment of Constipation Quality of Life total score was significantly decreased in the TEA group ( P = 0.004). (ii) Compared with sham-TEA, TEA improved colon transit ( P = 0.002) and increased the threshold of rectal sensation (desire to defecate, P = 0.004; maximum tolerability, P < 0.001). (iii) TEA increased vagal activity, compared with sham-TEA ( P < 0.05); at the end of the treatment, the vagal activity was significantly correlated with colon transit and the CSBMs/week. DISCUSSION: TEA improves constipation and symptoms of IBS by accelerating colon transit and reducing rectal sensation, possibly mediated by using the autonomic mechanisms.
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Síndrome del Colon Irritable , Dolor Abdominal/etiología , Dolor Abdominal/terapia , Colon , Estreñimiento/etiología , Estreñimiento/terapia , Tránsito Gastrointestinal , Humanos , Síndrome del Colon Irritable/complicaciones , Síndrome del Colon Irritable/terapia , Calidad de Vida , SensaciónRESUMEN
Considering the staggering global prevalence of local pain affecting hundreds of million individuals, it is of great significance to develop advanced dosage forms or delivery systems for analgesic therapy to fulfill clinical applicability. In this study, a hydrogel microneedles (MNs) system made out of gelatin-methacryloyl (GelMA) was designed to deliver lidocaine hydrochloride (LiH) in a sustained manner, and the drug loading capacity of the GelMA MNs was increased considerably by using the backing layer reservoir. The in vitro and in vivo tests showed that the fabricated GelMA MNs are strong enough for reliable skin application, and achieve high drug delivery efficiency as compared with the commercial lidocaine patches. The Spared-nerve injury (SNI) model of rats was also prepared to test behavioral pain sensitivity in response to mechanical stimuli, which proved that the LiH/GelMA MNs can enhance and prolong the anesthetic effect of LiH. In addition, with biosafety evaluation in rats, the MNs treated site restored to normal appearance within several hours of application and no dermatosis-related side effects or behavior disorders were observed during the experiment. Together these results indicated that the use of GelMA MNs for transdermal delivery of LiH is an effective, safe and simple treatment method to provide a better choice for local long-lasting analgesia.
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Analgesia , Lidocaína , Administración Cutánea , Animales , Lidocaína/farmacología , Agujas , Dolor/tratamiento farmacológico , RatasRESUMEN
Parkinson's disease (PD) always causes dyskinesia and cognitive impairments. The alpha-synuclein (α-syn) accumulation, one of the main pathological characteristics of PD, may impair synaptic structural and synaptic functions. Nano-MgO composites has been reported to interfere α-syn expression. The present study is aim to investigate the roles of nano-MgO composites on cognitive impairments in PD rats. PD rats were formed by 6-hydroxydopamine (6-OH DA) and α-syn expression were evaluated by Western blot. Hippocampal dendritic morphology was examined by Golgi staining. Morris water maze (MWM) test was applied to evaluate learning and memory abilities and population spike was recorded by electrophysiological records in vivo. The results showed that: 6-OH DA-treated up-regulated α-syn levels in striatum and hippocampus and increased the rotational times by APO, but nano-MgO composites could down-regulated α-syn levels. The overall length of dendritic and the total number of intersections were reduced by 6-OH DA, accompanied by the decrease of the dendritic spine density in hippocampal CA1, CA3 and DG regions. Interestingly, nano-MgO composites could alleviate the morphological damages of dendrites. In the MWM test, the escape latencies and the swimming distances in PD rats were increased as compared to the sham group, and nano-MgO composites could reduce the escapes latencies and the swimming distances. Furthermore, 6-OH DA reduced the amplitudes of long-term potentiation (LTP) in hippocampal CA1 region, and 6 mg/kg nano-MgO composites could improve LTP amplitudes. In conclusion, the current findings would be helpful to explore the roles of nano-MgO composites on neuroprotection in PD.
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Fármacos Neuroprotectores , Enfermedad de Parkinson , Animales , ADN , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Oxidopamina , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , Plásmidos , Ratas , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMEN
OBJECTIVE: This study aimed to find new biomarkers of prognosis and metabolomic therapy for gastric carcinoma (GC) treated with chemotherapy and investigate the metabolic mechanism of the Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction in the treatment of GC. METHODS: First, 36 patients with GC were randomly assigned to the treatment (chemotherapy plus JPYZXZ) and control (chemotherapy alone) groups. The clinical efficacy, side effects, and quality of life of patients in the two groups were evaluated after treatment. Then, the serum samples taken from 16 randomly selected patients (eight treatment cases and eight control cases with no evident pattern characters) and eight healthy volunteers were tested to identify the differential metabolite under the gas chromatography-time-of-fight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. RESULTS: JPYZXZ combined with chemotherapy resulted in a lower risk of leucopenia, thrombocytopenia, and gastrointestinal reaction (P < 0.05). Additionally, patients in the treatment group showed a higher Karnofsky (KPS) scale (P < 0.05). Compared with healthy persons, patients with GC were found to have 26 significant differential metabolites after chemotherapy; these metabolites are mainly involved in 12 metabolic pathways, such as valine, leucine, and isoleucine biosynthesis. JPYZXZ primarily influences the pentose phosphate pathway; glutathione metabolism; glyoxylate and dicarboxylate metabolism; porphyrin and chlorophyll metabolism; and glycine, serine, and threonine metabolism of patients with GC treated with chemotherapy. CONCLUSIONS: The metabolic characteristics of patients with GC after chemotherapy are mainly various amino acid metabolic defects, especially L-glutamine, L-leucine, L-alloisoleucine, and L-valine. These defects lead to a series of problems, such as decreased tolerance and effectiveness of chemotherapy, increased side effects, decreased immunity, and shortened survival time. In addition, the remarkable upregulation of the gluconolactone level in patients with GC suggests the high proliferative activity of GC cells. Thus, gluconolactone may be used as a potential prognostic and diagnostic evaluation index. Moreover, JPYZXZ can reduce the incidence of ADRs and improve the life quality of patients by the correction of L-glutamine, L-leucine, L-alloisoleucine, and L-valine metabolism deficiency. In addition, gluconolactone metabolism is inhibited by JPYZXZ. Such inhibition may be one of the antitumor mechanisms of JPYZXZ.
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BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. METHODS: The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. RESULTS: WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in-silico softwares. CONCLUSION: Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.
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Síndrome de Bardet-Biedl/metabolismo , Homocigoto , Mutación Missense , Linaje , Proteínas/genética , Adulto , Sustitución de Aminoácidos , Síndrome de Bardet-Biedl/patología , Femenino , Humanos , India , MasculinoRESUMEN
Although gene therapy targeting the α-synuclein gene (SNCA) has achieved outstanding results in the treatment of Parkinson's disease (PD), the lack of a suitable gene delivery system and inadequate therapeutic effects remains a tremendous obstacle for RNAi therapy. Here, a degradable nano-MgO micelle composite (MgO(pDNA)-INS-Plu-mRNA-NGF) with double interference (mediated by RNAi and α-synuclein (α-syn)-targeted mRNA) was constructed. Binding mRNA treatment significantly increased the inhibitory effect compared to the reduction of α-syn expression by RNAi alone. Moreover, the cell experiments demonstrated that the viability of the PD cell model can be significantly improved by nano-MgO micelle composite treatment. More importantly, the composite has the ability to penetrate the blood brain barrier and deliver genes and mRNA to neurons through endocytosis mediated by the nerve growth factor and its receptors, thus significantly downregulating the expression of α-syn in the PD mice model without causing damage to other major organs. Overall, this work provides a novel insight into the design of biomaterials for gene therapy for PD.
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Enfermedad de Parkinson , Animales , Ratones , Micelas , Neuronas/metabolismo , Enfermedad de Parkinson/terapia , Interferencia de ARN , alfa-Sinucleína/genéticaRESUMEN
Metaplasticity is referred to adjustment in the requirements for induction of synaptic plasticity based on the prior history of activity. Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), has been considered to be the neural processes underlying learning and memory. Previous observations that cordycepin (an adenosine derivative) improved learning and memory seemed to be contradictory to the findings that cordycepin inhibited LTP. Therefore, we speculated that the conflicting reports of cordycepin might be related to metaplasticity. In the current study, population spike (PS) in hippocampal CA1 area of rats was recorded by using electrophysiological method in vivo. The results showed that cordycepin reduced PS amplitude in hippocampal CA1 with a concentration-dependent relationship, and high frequency stimulation (HFS) failed to induce LTP when cordycepin was intrahippocampally administrated but improved LTP magnitude when cordycepin was pre-treated. Cordycepin increased LTD induced by activating N-Methyl-D-aspartate (NMDA) receptors and subsequently facilitated LTP induced by HFS. Furthermore, we found that 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A1 receptors antagonist, could block the roles of cordycepin on LTD and LTP. Collectively, cordycepin was able to modulate metaplasticity in hippocampal CA1 area of rats through adenosine A1 receptors. These findings would be helpful to reconcile the conflicting reports in the literatures and provided new insights into the mechanisms underlying cognitive function promotions with cordycepin treatment.
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Agonistas del Receptor de Adenosina A1/farmacología , Región CA1 Hipocampal/efectos de los fármacos , Desoxiadenosinas/farmacología , Plasticidad Neuronal/efectos de los fármacos , Receptor de Adenosina A1/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Región CA1 Hipocampal/metabolismo , Potenciación a Largo Plazo/efectos de los fármacos , Depresión Sináptica a Largo Plazo/efectos de los fármacos , Masculino , Ratas Sprague-Dawley , Receptor de Adenosina A1/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Factores de TiempoRESUMEN
Cordycepin exerted significant neuroprotective effects and protected against cerebral ischemic damage. Learning and memory impairments after cerebral ischemia are common. Cordycepin has been proved to improve memory impairments induced by cerebral ischemia, but its underlying mechanism has not been revealed yet. The plasticity of synaptic structure and function is considered to be one of the neural mechanisms of learning and memory. Therefore, we investigated how cordycepin benefits dendritic morphology and synaptic transmission after cerebral ischemia and traced the related molecular mechanisms. The effects of cordycepin on the protection against ischemia were studied by using global cerebral ischemia (GCI) and oxygen-glucose deprivation (OGD) models. Behavioral long-term potentiation (LTP) and synaptic transmission were observed with electrophysiological recordings. The dendritic morphology and histological assessment were assessed by Golgi staining and hematoxylin-eosin (HE) staining, respectively. Adenosine A1 receptors (A1R) and adenosine A2A receptors (A2AR) were evaluated with western blotting. The results showed that cordycepin reduced the GCI-induced dendritic morphology scathing and behavioral LTP impairment in the hippocampal CA1 area, improved the learning and memory abilities, and up-regulated the level of A1R but not A2AR. In the in vitro experiments, cordycepin pre-perfusion could alleviate the hippocampal slices injury and synaptic transmission cripple induced by OGD, accompanied by increased adenosine content. In addition, the protective effect of cordycepin on OGD-induced synaptic transmission damage was eliminated by using an A1R antagonist instead of A2AR. These findings revealed that cordycepin alleviated synaptic dysfunction and dendritic injury in ischemic models by modulating A1R, which provides new insights into the pharmacological mechanisms of cordycepin for ameliorating cognitive impairment induced by cerebral ischemia.
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Parkinson's disease (PD) is characterized by motor and non-motor symptoms, primarily affecting dopaminergic neurons (DAergic neurons) in substantia nigra (SN). However, it is still very challenging to identify new drugs that not only inhibit motor dysfunction but also improve non-motor dysfunction. It has been identified as a potential PD treatment that the inhibition of α-syn aggregation could decrease the death of DAergic neurons in SN. In this study, we synthesized gold nanoparticle composites (NPs) that were loaded with plasmid DNA (pDNA) to inhibit α-syn expression. In vivo, our results showed that NPs improved tyrosine hydroxylase (TH) levels and decreased aggregation of α-syn in the SN. Additionally, NPs attenuated motor dysfunction and exploration ability declined. Moreover, NPs reversed the inhibition of long-term potentiation (LTP) and improved non-motor dysfunction in PD mice. These results indicated that NPs had significantly neuroprotective effects not only in motor, but also in non-motor dysfunction to PD mice, providing a new strategy for gene therapy in PD.
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Disfunción Cognitiva , Nanopartículas del Metal , Enfermedad de Parkinson , Animales , Modelos Animales de Enfermedad , Oro , Ratones , Ratones Endogámicos C57BL , Enfermedad de Parkinson/tratamiento farmacológico , Sustancia NegraRESUMEN
BACKGROUND: Congenital atrichia (CA) is a rare form of irreversible alopecia with an autosomal recessive mode of inheritance. This form of hair loss is mainly associated with mutations in the human hairless (HR) gene located at chromosome 8p21.3. An additional unique feature atrichia with papular lesions (APL) comprises keratin-filled cysts known as papules. The present study aimed to uncover the underlying genetic causes of APL in two consanguineous Kashmiri families. METHODS: In the present study, two consanguineous families of Kashmiri origin with APL displaying an autosomal recessive mode of inheritance were investigated. Whole exome and Sanger sequencing followed by bioinformatic studies, variant prioritization, Sanger validation and segregation analysis was performed to find the mutation. RESULTS: A recurrent nonsense (NM_005144: c.2818C > T:p.Arg940*) mutation was detected in exon 13 of the human HR gene. CONCLUSIONS: Whole exome sequencing analysis has widely been used in the screening of single gene disorders mutations, both in research and diagnostic laboratories. Sanger sequencing alone for genes such as HR becomes expensive and time consuming. Instead, it is recommended that a patient is to screen by whole exome sequencing and then special attention first focuses on known genes of the APL phenotype. This is helpful for intime diagnosis, being more efficient and economic. The results obtained in the present study may contribute to prenatal diagnosis, carrier secreening and the genetic counseling of families with the APL phenotype in Kashmiri poplution.
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Alopecia/diagnóstico , Alopecia/genética , Exones/genética , Folículo Piloso/anomalías , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/genética , Factores de Transcripción/genética , Alelos , Alopecia/sangre , Alopecia/patología , Codón sin Sentido , Familia , Femenino , Humanos , Masculino , Mutación , Pakistán , Linaje , Fenotipo , Enfermedades Cutáneas Vesiculoampollosas/sangre , Secuenciación del ExomaRESUMEN
PURPOSE: Thalamic hemorrhage breaking into ventricles (THBIV) is a devastating disease with high morbidity and mortality rates. Endoscopic surgery (ES) may improve outcomes, although there is no consensus on its superiority. We investigated the efficacy and safety of ES and compared the outcomes of different management strategies by ES, hematoma puncture and drainage (HPD), and external ventricular drainage (EVD) in patients with THBIV. METHODS: We retrospectively analyzed patients with THBIV treated by ES, HPD, or EVD at our hospital from June 2015 to June 2018. Patients were categorized into anteromedial and posterolateral groups based on THBIV location, and then the two groups were further divided into ES, HPD, and EVD subgroups. Individualized surgical approach was adopted according to the location of the hematoma in the ES subgroups. Patient characteristics and surgical outcomes were investigated. RESULTS: We analyzed 211 consecutive patients. There were no significant differences in clinical characteristics or incidence of perioperative procedure-related complications (postoperative rebleeding and intracranial infection) in either anteromedial or posterolateral groups. Compared with other therapeutic methods, the ES subgroups had the highest hematoma evacuation rate, shortest drainage time, and lowest incidence of chronic ventricular dilatation (all p < 0.05). Among the three anteromedial subgroups, ES subgroup had the best clinical outcomes which was assessed by the modified Rankin Scale, followed by HPD and EVD subgroups (p < 0.01); while in the posterolateral subgroups, clinical outcomes in the ES and HPD subgroups were similar and better than that in the EVD subgroup (p = 0.037). CONCLUSION: Individualized surgical ES approach for removal of thalamic and ventricular hematomas is a minimally invasive, safe, and effective strategy for the treatment of THBIV with a thalamic hematoma volume of 10-30 mL.
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Hemorragia Cerebral/cirugía , Ventrículos Cerebrales/cirugía , Endoscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Paracentesis/métodos , Tálamo/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Cordycepin, an adenosine analog, has been reported to improve cognitive function, but which seems to be inconsistent with the reports showing that cordycepin inhibited long-term potentiation (LTP). Behavioral-LTP is usually used to study long-term synaptic plasticity induced by learning tasks in freely moving animals. In order to investigate simultaneously the effects of cordycepin on LTP and behavior in rats, we applied the model of behavioral-LTP induced by Y-maze learning task through recording population spikes in hippocampal CA1 region. Golgi staining and Sholl analysis were employed to assess the morphological structure of dendrites in pyramidal cells of hippocampal CA1 area, and western blotting was used to examine the level of adenosine A1 receptors and A2A receptors (A2AR). We found that cordycepin significantly improved behavioral-LTP magnitude, accompanied by increases in the total length of dendrites, the number of intersections and spine density but did not affect Y-maze learning task. Furthermore, cordycepin obviously reduced A2AR level without altering adenosine A1 receptors level; and the agonist of A2AR (CGS 21680) rather than antagonist (SCH 58261) could reverse the potentiation of behavioral-LTP induced by cordycepin. These results suggested that cordycepin improved behavioral-LTP and morphological structure of dendrite in hippocampal CA1 but did not contribute to the improvement of learning and memory. And cordycepin improved behavioral-LTP may be through reducing the level of A2AR in hippocampus. Collectively, the effects of cordycepin on cognitive function and LTP were complex and involved multiple mechanisms.
Asunto(s)
Región CA1 Hipocampal/efectos de los fármacos , Dendritas/efectos de los fármacos , Desoxiadenosinas/farmacología , Potenciación a Largo Plazo/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Animales , Masculino , Células Piramidales/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Cerebral ischemia impairs physiological form of synaptic plasticity such as long-term potentiation (LTP). Clinical symptoms of cognitive dysfunction resulting from cerebral ischemia are associated with neuron loss and synaptic function impairment in hippocampus. It has been widely reported that cordycepin displays neuroprotective effect on ameliorating cognitive dysfunction induced by cerebral ischemia. Therefore, it is necessary to study whether cordycepin recovers cognitive function after brain ischemia through improving LTP induction. However, there has been very little discussion about the effects of cordycepin on LTP of cerebral ischemia so far. In the present study, we investigated the effects of cordycepin on LTP impairment and neuron loss induced by cerebral ischemia and excitotoxicity, using electrophysiological recording and Nissl staining techniques. The models were obtained by bilateral common carotid artery occlusion (BCCAO) and intrahippocampal NMDA microinjection. We also explored whether adenosine A1 receptors involve in the neuroprotection of cordycepin by using western blot. We found that cordycepin remarkably alleviated LTP impairment and protected pyramidal cell of hippocampal CA1 region against cerebral ischemia and excitotoxicity. Meanwhile, cordycepin prevented the reduction on adenosine A1 receptor level caused by ischemia but did not alter the adenosine A2A receptor level in hippocampal CA1 area. The improvement of LTP in the excitotoxic rats after cordycepin treatment could be blocked by DPCPX, a selective antagonist of adenosine A1 receptor. In summary, our findings provided new insights into the mechanisms of cordycepin neuroprotection in excitotoxic diseases, which is through regulating adenosine A1 receptor to improve LTP formation and neuronal survival.