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Alzheimer's disease (AD), the most common cause of dementia worldwide, is mainly characterized by the aggregated ß-amyloid (Aß) and hyperphosphorylated tau. Safflower yellow (SY) is a novel water extract of natural safflower and has been suggested to ameliorate memory deficits in several animal models of dementia. In this study, we aimed to investigate the effect and mechanism of SY on deficits of learning and memory and hyperphosphorylation of tau in APP/PS1 double transgenic mice. APP/PS1 mice were administered with SY (10, 30, 100 mg/kg) by oral gavage for three months at the age of six months. The ability of learning and memory was investigated using the step-down test and Morris water maze test, and protein level in the brain was evaluated using western blot. Here, we found that SY treatment can improve spatial learning and memory ability, and reduce tau hyperphosphorylation at Ser199, Thr205, Ser396, Ser404 sites in APP/PS1 mice. In addition, the activity the of cyclin-dependent kinase 5 (CDK-5) and glycogen synthase kinase 3ß (GSK-3ß), major kinases involved in tau phosphorylation, was siginificantly decreased in APP/PS1 mice by SY treatment. These results support SY can serve as a promising multitarget neuronal therapeutic agent for the treatment of AD.
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Precursor de Proteína beta-Amiloide/genética , Chalcona/análogos & derivados , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/genética , Presenilina-1/genética , Proteínas tau/metabolismo , Animales , Chalcona/farmacología , Chalcona/uso terapéutico , Trastornos del Conocimiento/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Fosforilación/efectos de los fármacos , Fosforilación/fisiología , Proteínas tau/antagonistas & inhibidoresRESUMEN
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common disorders in child and adolescent psychiatry, with a prevalence of more than 5%. Despite extensive research on ADHD in the last 10 to 20 years, effective treat-ments are still lacking. Instead, the concept of ADHD seems to have become broader and more heterogeneous. Therefore, the diagnosis and treatment of ADHD remains challenging for clinicians. AIM: To investigate the effects of a multimodal integrated intervention for children with ADHD. METHODS: Between March 2019 and September 2020, a total of 100 children with ADHD who were diagnosed and treated at our hospital were assessed for eligibility, two of whom revoked their consent. A case-control study was conducted in which the children were equally assigned, using a randomized number table, to either a medication group (methylphenidate hydrochloride extended-release tablets and atomoxetine hydrochloride tablets) or a multimodal integrated intervention group (medication + parent training + behavior modification + sensory integration therapy + sand tray therapy), with 49 patients in each group. The clinical endpoint was the efficacy of the different intervention modalities. RESULTS: The two groups of children with ADHD had comparable patient characteristics (P > 0.05). Multimodal integrated intervention resulted in a significantly higher treatment efficacy (91.84%) than medication alone (75.51%) (P < 0.05). Children who received the multimodal integrated intervention showed lower scores in the Conners Parent Symptom Questionnaire and the Weiss Functional Impairment Rating Scale than those treated with medication alone (P < 0.05). The Sensory Integration Scale scores of children in the multimodal integrated intervention group were higher than those of children in the medication group (P < 0.05). Children who received the multimodal integrated intervention had higher compliance and family satisfaction and a lower incidence of adverse events than those treated with medication alone (P < 0.05). CONCLUSION: Multimodal integrated intervention effectively alleviated symptoms associated with ADHD in children. It enhanced their memory and attention with high safety and parental satisfaction, demonstrating good potential for clinical promotion.
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BACKGROUND: Long-term treatment of attention deficit/hyperactivity disorder (ADHD) is associated with adverse events, such as nausea and vomiting, dizziness, and sleep disturbances, and poor maintenance of late ADHD medication compromises treatment outcomes and prolongs the recovery of patients' social functioning. AIM: To evaluate the effect of non-pharmacological treatment on the full recovery of social functioning in patients with ADHD. METHODS: A total of 90 patients diagnosed with ADHD between May 2019 and August 2020 were included in the study and randomly assigned to either the pharmacological group (methylphenidate hydrochloride and tomoxetine hydrochloride) or the non-pharmacological group (parental training, behavior modification, sensory integration therapy, and sand tray therapy), with 45 cases in each group. Outcome measures included treatment compliance, Swanson, Nolan, and Pelham, Version IV (SNAP-IV) scores, Conners Parent Symptom Questionnaire (PSQ) scores, and Weiss Functional Impairment Rating Scale (WFIRS) scores. RESULTS: The non-pharmacological interventions resulted in significantly higher compliance in patients (95.56%) compared with medication (71.11%) (P < 0.05). However, no significant differences in SNAP-IV and PSQ scores, in addition to the learning/school, social activities, and adventure activities of the WFIRS scores were observed between the two groups (P > 0.05). Patients with non-pharmacological interventions showed higher WFIRS scores for family, daily life skills, and self-concept than those in the pharmacological group (P < 0.05). CONCLUSION: Non-pharmacological interventions, in contrast to the potential risks of adverse events after long-term medication, improve patient treatment compliance, alleviate patients' behavioral symptoms of attention, impulsivity, and hyperactivity, and improve their cognitive ability, thereby improving family relationships and patient self-evaluation.
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Adults and larvae of the family Philopotamidae from Zhejiang Province, China, were examined and mtCOI gene sequences were extracted and analyzed, males and larvae of 3 species were successfully associated. The larvae of Chimarra sadayu Malicky 1993, Dolophilodes bellatula Sun Malicky 2002, Wormaldia unispina Sun 1998 are described in detail and their diagnostic photographs and illustrations are presented. Diagnostic characters for genera and species are discussed.
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Holometabola , Insectos , Animales , China , Larva , MasculinoRESUMEN
The adult male and larva of a new species in the genus Chimarra Stephens, Chimarra paramonorum n. sp., are described, diagnosed, and illustrated based on the specimens collected in Zhejiang Province, China. The larva and adult male were associated by mtCOI gene sequences. The male can be separated from C. monorum and C. thienemanni mainly by small preanal appendages and by wrinkled, hairless endotheca. The larva of the new species can be separated from other congeners by a combination of characters including the notch on the anterior margin of the frontoclypeus, the teeth of the mandibles, and the length of the seta-bearing process of each forecoxa. The larval description is the first for Chimarra in China.
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Insectos , Animales , China , Larva , MasculinoRESUMEN
Safflower yellow (SY), one of traditional Chinese medicine extracted from safflower, has been shown to have neuroprotective effects on animal models of vascular dementia and Alzheimer's diseases (AD), by inhibiting oxidative injury, neuronal apoptosis and tau hyperphosphorylation. In this study, we investigated whether safflower yellow (SY) can improve cognitive function, decrease Amyloid ß (Aß) accumulation and overactivation of astrocytes in AD mouse model. We found that SY treatment significantly ameliorated the learning and memory deficits of APP/PS1 mice. By hematoxylin-eosin staining, we found that the neuronal loss and death in APP/PS1 mice was decreased by SY treatment. Immunohistochemical staining showed that SY treatment dramatically down-regulated Aß1-42 deposition and glial fibrillary acidic protein (GFAP) level in APP/PS1 mice. Biochemical analysis also showed that SY treatment reduced soluble and insoluble Aß1-42 level in the cortex and soluble Aß1-42 level in the hippocampus of APP/PS1 mice. Moreover, we found that SY treatment decreased the expression of proteins related to generation of Aß, and markedly increased expression of enzymes associated with clearance of Aß in the brain of APP/PS1 mice. These results indicate that the SY can serve as a promising therapeutic approach for the treatment of AD.
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Péptidos beta-Amiloides/metabolismo , Astrocitos/efectos de los fármacos , Chalcona/análogos & derivados , Hipocampo/efectos de los fármacos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Astrocitos/metabolismo , Chalcona/farmacología , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/metabolismo , Hipocampo/metabolismo , Masculino , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
Immunohistochemical distribution and cellular localization of neurotrophins was investigated in adult monkey brains using antisera against nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Western blot analysis showed that each antibody specifically recognized appropriate bands of approximately 14.7 kDa, 14.2 kDa, 13.6 kDa, and 14.5 kDa, for NGF, BDNF, NT-3, and NT-4, respectively. These positions coincided with the molecular masses of the neurotrophins studied. Furthermore, sections exposed to primary antiserum preadsorbed with full-length NGF, BDNF, NT-3, and NT-4 exhibited no detectable immunoreactivity, demonstrating specificities of the antibodies against the tissues prepared from rhesus monkeys. The study provided a systematic report on the distribution of NGF, BDNF, NT-3, and NT-4 in the monkey brain. Varying intensity of immunostaining was observed in the somata and processes of a wide variety of neurons and glial cells in the cerebrum, cerebellum, hippocampus, and other regions of the brain. Neurons in some regions such as the cerebral cortex and the hippocampus, which stained for neurotrophins, also expressed neurotrophic factor mRNA. In some other brain regions, there was discrepancy of protein distribution and mRNA expression reported previously, indicating a retrograde or anterograde action mode of neurotrophins. Results of this study provide a morphological basis for the elucidation of the roles of NGF, BDNF, NT-3, and NT-4 in adult primate brains.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Encéfalo/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Neurotrofina 3/metabolismo , Animales , Especificidad de Anticuerpos , Encéfalo/anatomía & histología , Inmunohistoquímica , Macaca mulatta , Neuroglía/metabolismo , Neuronas/metabolismoRESUMEN
OBJECTIVE: To investigate the distribution and change of NGF, BDNF and NT3 in hippocampus of rat with Alzheimer disease(AD) by immunohistochemistry. METHODS: AD model was established by injecting beta amyloid protein into the hippocampus of rat. The rats were killed ten days after injection. The hippocampus sections were made coronally on a freezing microtome. Brain sections were processed by immunohistochemical procedure with molocloned antibodies against NGF, BDNF and NT3. The number of positive neurons of NGF, BDNF and NT3 was counted and analyzed statistically. RESULTS: It was found that the number of NGF positive neurons increased and the immunostaining intensity became stronger as compared with the control (P<0.01). The number of BDNF positive neurons decreased and the immunostaining intensity weakened (P<0.01). There Our was no change in the number and immunostaining intensity of NT3 positive neurons (P>0.05). CONCLUSION: results show that NGF, BDNF, NT3 have experienced different changes in hippocampus of rat with AD, suggesting that they play different roles in the course of AD and bear relation to the physiological function of cholinergic neurons in hippocampus of rat with AD. In particular, BDNF exerts crucial effect on the degeneration of neuronal function in the hippocampus of rat with AD.
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Enfermedad de Alzheimer/metabolismo , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Hipocampo/metabolismo , Factores de Crecimiento Nervioso/biosíntesis , Neurotrofina 3/biosíntesis , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Femenino , Factores de Crecimiento Nervioso/genética , Neurotrofina 3/genética , RatasRESUMEN
Insoluble plaques of amyloid ß proteins (Aß) and neurofibrillary tangles of hyperphosphorylated tau are key markers for Alzheimer's disease (AD). Safflower yellow (SY) is one of traditional Chinese medicine extracted from safflower, which is suggested to have therapeutic potential for neurodegenerative disorders. However, whether SY can ameliorate impairment of learning and memory in AD model, and its causal mechanism are still unclear. Here, we applied different doses of SY intragastrically to Wistar rats injected with amyloid ß (1-42) for 1 month. By the Morris water maze test, we found that treatment of SY significantly attenuated amyloid ß (1-42)-induced impairment of memory in rats. Mechanistically, SY treatment increased the level of superoxidedismutase (SOD) and Glutathione peroxidase (GSH-Px), and decreased the level of malondialdehyde (MDA) and acetylcholinesterase (T-CHE) in brain tissues of AD rats. Pathological analysis also showed that SY treatment inhibited the morphological alteration of neurons and tau hyperphosphorylation induced by amyloid ß (1-42)-injection in the cortex and hippocampus. Moreover, SY treatment inhibited CDK-5 and GSK-3 signaling pathways, which are upregulated in AD rats. Our data indicate that safflower yellow can serve as a therapeutic candidate for Alzheimer's disease.
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Enfermedad de Alzheimer/tratamiento farmacológico , Chalcona/análogos & derivados , Peroxidación de Lípido/efectos de los fármacos , Trastornos de la Memoria/prevención & control , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides/toxicidad , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Chalcona/administración & dosificación , Chalcona/farmacología , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Neuronas/patología , Fragmentos de Péptidos/toxicidad , Fosforilación/efectos de los fármacos , Ratas , Ratas Wistar , Proteínas tau/metabolismoRESUMEN
BACKGROUND:Various methods are involved in the treatment of adolescent idiopathic scoliosis (AIS),and functional rehabilitation training can provide support for clinical rehabilitation.OBJECTIVE:To explore the ipositive effects of exercise on the weak links of spinal mechanical disturbance,and to fully improve AIS through sport rehabilitation.METHODS:Nineteen AIS patients were randomly divided into experimental (n=10) and control (n=9) groups,followed by given manual reduction combined with functional rehabilitation training,or manual reduction combined with conventional strength training.The shape of the spine was acquired under different postures using X-ray and Spinalmouse.The spinal lateral flexion strength was assessed by Back-Check tester.The range of motion of the waist was measured by joint angle measurement apparatus.The patients' subjective feeling was measured through Scoliosis Research Society-22 questionnaire.All data underwent t-test.RESULTS AND CONCLUSION:After 32-week intervention,the Cobb angle and distance of top cone deviating from the midline of sacrum had significant difference between experimental and control groups (F < 0.05).The experimental group patients had the sagittal spinal joint angle that was closer to the physiological curve.There was a significant difference in the muscle strength between experimental and control groups (P < 0.05).The range of motion of the waist under anteflexion,as well as posterior extension and right lateroflexion showed significant difference between experimental and control groups (P <0.01,P < 0.05).The Scoliosis Research Society-22 Questionnaire scores in the experimental group were significantly higher than those in the control group (P < 0.05).These results indicate that functional rehabilitation training can improve the control ability of deep muscle groups and muscle strength and endurance.
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Taking Meizao/Dongbeishanyingtao (Prunus serrulata G. Don) and Meizao/Mahaleb (P. mahaleb L.) as test materials, the respiration intensity and respiratory enzyme activities of their growing roots and brown lignified roots were determined under waterlogging. The results showed that under waterlogging, the root respiration intensity of the two kind rootstocks had a decreasing trend, with more decrement for their growing roots. For P. serrulata, the decrement of the respiration intensity of its growing roots and brown lignified roots was 1.47 and 1.36 times as much as that of P. mahaleb, respectively. The pyruvate decarboxylase (PDC) and lactate dehydrogenase (LDH) activities of the two kind roots had a decrease after an initial increase. Alcohol dehydrogenase (ADH) activity in growing roots also had a decrease after an initial increase, but that in brown lignified roots had an increasing trend. The test three enzyme activities changed more in growing roots than in brown lignified roots. The increment of ADH and LDH activities was higher for P. serrulata than for P. mahaleb, while PDC activity was in adverse. The malate dehydrogenase (MDH) activity of the two kind roots decreased, and the decrement was larger in growing roots than in brown lignified roots. P. serrulata had a larger decrement of root MDH activity than P. mahaleb To the waterlogging stress, growing roots was more sensitive than brown lignified roots, and P. serrulata was more sensitive than P. mahaleb.
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Raíces de Plantas/enzimología , Raíces de Plantas/metabolismo , Prunus/enzimología , Prunus/metabolismo , Alcohol Deshidrogenasa/metabolismo , Respiración de la Célula , Inundaciones , Malato Deshidrogenasa/metabolismo , Piruvato Descarboxilasa/metabolismoRESUMEN
A novel assay of gamma-globulin (gamma-IgG) with a sensitivity at the nanogram level is proposed based on the measurement of enhanced resonance light-scattering (RLS) signals resulting from the interaction of functionalized nano-HgS with gamma-globulin. At pH 5.03, the RLS signals of functionalized nano-HgS were greatly enhanced by gamma-globulin in the region of 200-700nm characterized by the peak around 362nm. Linear relationship can be established between the enhanced RLS intensity and gamma-globulin concentration in the range of 10-140ngml(-1). The limit of detection is 2.71ngml(-1). Based on this, a new direct quantitative determination method for gamma-globulin in blood serum samples without separation of human serum albumin (HSA) is established. The contents of gamma-IgG in blood serum samples were determined with recovery of 95.7-102.5% and R.S.D. of 1.6-2.4%. This method is proved to be very sensitive, rapid, simple and tolerance of most interfering substances.