RESUMO
BACKGROUND AND OBJECTIVE: Cerebral small vessel disease (CSVD) often coexists with cognitive dysfunction in patients, leading to significant challenges in treatment and management. This study aimed to examine the efficacy of combined application of donepezil and nimodipine on patients with comorbid CSVD and cognitive dysfunction and the effects on patients' albumin and prealbumin levels. METHODS: The records of 112 patients with comorbid CSVD and cognitive dysfunction treated at the People's Hospital of Suzhou New District from January 2019 to December 2022 were analysed retrospectively. A total of 50 patients receiving donepezil were allocated to the control group, and 62 patients receiving both nimodipine and donepezil to the study group. Outcomes compared between the two groups included serum homocysteine (Hcy), high sensitivity C-reactive protein (hs-CRP), albumin, and prealbumin before and after therapy, efficacy, and adverse reactions. Additionally, logistic regression was performed to analyze the risk factors impacting patient prognosis. RESULTS: Prior to therapy, the two groups did not differ significantly in Hcy and hs-CRP levels (p > 0.05), whereas after therapy, the levels in both groups dropped significantly (p < 0.01), with more obvious lower levels in the study group (p < 0.05). After treatment, the study group presented significantly higher albumin and prealbumin levels than the control group (p < 0.001). An obvious higher overall response rate was observed in the study group compared to the control group (p = 0.012). No significant inter-group discrepancy was found regarding the total incidence of adverse reactions (p = 0.752). Univariate analysis identified age, course of disease, heart rate (HR), Montreal Cognitive Assessment (MoCA) score, diastolic blood pressure (DBP), systolic blood pressure (SBP), drinking history, as well as medication regimen as risk factors impacting patient prognosis. Multivariate logistic regression analysis identified SBP, DBP, and medication regimen as the independent risk factors. CONCLUSION: Combined application of donepezil and nimodipine can effectively treat patients with comorbid CSVD and cognitive dysfunction. It can significantly lower the Hcy and hs-CRP levels and improve the nutritional status without increasing the frequency of adverse reactions. In addition, for CSVD patients with cognitive dysfunction, age, course of disease, MoCA score, HR, SBP, DBP, drinking history, and medication regimen are risk factors impacting patient prognosis, while SBP, DBP, and medication regimen are independent risk factors.
Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Donepezila , Quimioterapia Combinada , Nimodipina , Estado Nutricional , Humanos , Feminino , Masculino , Donepezila/administração & dosagem , Donepezila/uso terapêutico , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Doenças de Pequenos Vasos Cerebrais/complicações , Disfunção Cognitiva/tratamento farmacológico , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Nimodipina/administração & dosagem , Nimodipina/uso terapêutico , Resultado do Tratamento , Nootrópicos/administração & dosagem , Nootrópicos/uso terapêutico , Nootrópicos/efeitos adversos , Homocisteína/sangueRESUMO
BACKGROUND: Depression is one of the most common psychiatric diseases. The monoamine transmitter theory suggests that neurotransmitters are involved in the mechanism of depression; however, the regulation on serotonin production is still unclear. We previously showed that Ahi1 knockout (KO) mice exhibited depression-like behavior accompanied by a significant decrease in brain serotonin. METHODS: In the present study, western blot, gene knockdown, immunofluorescence, dual-luciferase reporter assay, and rescue assay were used to detect changes in the Ahi1/GR/ERß/TPH2 pathway in the brains of male stressed mice and male Ahi1 KO mice to explain the pathogenesis of depression-like behaviors. In addition, E2 levels in the blood and brain of male and female mice were measured to investigate the effect on the ERß/TPH2 pathway and to reveal the mechanisms for the phenomenon of gender differences in depression-like behaviors. RESULTS: We found that the serotonin-producing pathway-the ERß/TPH2 pathway was inhibited in male stressed mice and male Ahi1 KO mice. We further demonstrated that glucocorticoid receptor (GR) as a transcription factor bound to the promoter of ERß that contains glucocorticoid response elements and inhibited the transcription of ERß. Our recent study had indicated that Ahi1 regulates the nuclear translocation of GR upon stress, thus proposing the Ahi1/GR/ERß/TPH2 pathway for serotonin production. Interestingly, female Ahi1 KO mice did not exhibit depressive behaviors, indicating sexual differences in depressive behaviors compared with male mice. Furthermore, we found that serum 17ß-estradiol (E2) level was not changed in male and female mice; however, brain E2 level significantly decreased in male but not female Ahi1 KO mice. Further, ERß agonist LY-500307 increased TPH2 expression and 5-HT production. Therefore, both Ahi1 and E2 regulate the ERß/TPH2 pathway and involve sexual differences in brain serotonin production and depressive behaviors. CONCLUSIONS: In conclusion, although it is unclear how Ahi1 controls E2 secretion in the brain, our findings demonstrate that Ahi1 regulates serotonin production by the GR/ERß/TPH2 pathway in the brain and possibly involves the regulation on sex differences in depressive behaviors. Video Abstract.
Assuntos
Receptores de Glucocorticoides , Serotonina , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Encéfalo/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Masculino , Camundongos , Camundongos Knockout , Receptores de Glucocorticoides/metabolismo , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismoRESUMO
Odorant binding proteins (OBPs) are believed to be important for transporting semiochemicals through the aqueous sensillar lymph to the olfactory receptor cells within the insect antennal sensilla. In this study, three new putative OBP genes, MmedOBP8-10, were identified from a Microplitis mediator (Hymenoptera: Braconidae) antennal cDNA library. Quantitative real-time PCR (qRT-PCR) analysis revealed that all three of the OBP genes were expressed mainly in the antennae of adult wasps. The three OBPs were recombinantly expressed in Escherichia coli and purified by Ni ion affinity chromatography. Fluorescence competitive binding assays were performed using N-phenyl-naphthylamine as a fluorescent probe and 45 small organic compounds as competitors. These assays demonstrated that the three M. mediator OBPs can bind a broad range of odorant molecules with different binding affinities. They can bind the following ligands: nonane, farnesol, nerolidol, nonanal, ß-ionone, acetic ether, and farnesene. In a Y-tube assay with these ligands as odor stimuli and paraffin oil as a control, all ligands, except nerolidol and acetic ether, were able to elicit behavioral responses in adult M. mediator. The wasps were significantly attracted to ß-ionone, nonanal, and farnesene and repelled by nonane and farnesol. The results of this work provide insight into the chemosensory functions of the OBPs in M. mediator.
Assuntos
Himenópteros , Proteínas de Insetos/metabolismo , Receptores Odorantes/metabolismo , 1-Naftilamina/análogos & derivados , 1-Naftilamina/metabolismo , Aldeídos , Animais , Antenas de Artrópodes , Comportamento Animal , Feminino , Corantes Fluorescentes/metabolismo , Regulação da Expressão Gênica , Himenópteros/genética , Proteínas de Insetos/genética , Masculino , Dados de Sequência Molecular , Norisoprenoides , Receptores Odorantes/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
At present, microbial dust suppressants based on microbial communities lack necessary systematic analysis of factors affecting dust suppression performance. Therefore, in this study, the response surface curve method was used to optimize the culture conditions for enrichment of urease-producing microorganisms from activated sludge. The results indicated that when urea = 9.67 g L-1, NH4Cl = 5.21 g L-1, and pH = 9.57, the maximum urease activity of urease-producing microbial community (UPMC) was 8.22 mM min-1. The UPMC under optimized culture conditions reached a mineralization rate of 98.8% on the 1st day of mineralization. Ureolysis is one of the biological mechanisms that trigger microbial mineralization with the consequent effect of dust suppression. The analysis of microbial community structure indicated that the urease-producing bacteria Sporosarcina sp. had the highest abundance at the genus level in the microbial-based dust suppressant compound. Jeotgalicoccus sp. plays an important role in improving and maintaining the stability of urease. In addition, the optimal UPMC had low pathogenicity, which is extremely attractive for the safe application of microbial dust suppressants.
Assuntos
Carbonato de Cálcio , Poeira , Urease/química , Bactérias , UreiaRESUMO
BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1ß and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.
Assuntos
Doenças Cardiovasculares , Hipertensão Pulmonar , Humanos , Hematopoiese Clonal , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/genética , Hematopoese/genética , Doenças Cardiovasculares/genética , MutaçãoRESUMO
Odorant receptors are thought to play critical roles in the perception of chemosensory stimuli by insects. The primary method to address the functions of odorant receptors in insects is to use in vitro binding assays between the receptors and potential chemical stimuli. We injected MmedOrco dsRNA into the abdominal cavity of a braconid wasp, Microplitis mediator, and assayed for expression of this gene 72 h after treatment (RNAi). Quantitative real-time PCR demonstrated that the level of mRNA expression in MmedOrco dsRNA-treated M. mediator was significantly reduced (>90%) when compared with water-treated controls. Furthermore, electroantennogram (EAG) responses of M. mediator to two chemical attractants, nonanal and farnesene, were also reduced significantly (~70%) in RNAi-treated M. mediator when compared to controls. RNAi-treated M. mediator also responded by walking/flying at a lower rate to both chemicals when compared with controls in a Y-tube olfactometer bioassay, which provides direct evidence that MmedOrco plays an important role in perception of nonanal and farnesene in M. mediator.
Assuntos
Proteínas de Insetos/metabolismo , Feromônios/metabolismo , Receptores Odorantes/metabolismo , Vespas/fisiologia , Aldeídos/metabolismo , Animais , Comportamento Animal , Fenômenos Eletrofisiológicos , Feminino , Voo Animal , Proteínas de Insetos/genética , Masculino , Interferência de RNA , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores Odorantes/genética , Sesquiterpenos/metabolismo , Caminhada , Vespas/genética , Vespas/metabolismoRESUMO
Nature-based recreation in urban areas is essential for the well-being of citizens. Park green space (PGS) is a necessary urban infrastructure and a critical step of urban planning and policy-making. The existing research on PGS only focuses on service allocation problems existing in the current urban development, ignoring changes in residential communities accessibility. This research provides new ideas to evaluate PGS. Based on parks and residential communities' data, we adopt an improved Gaussian-based two-step floating catchment area (2SFCA) method to evaluate PGS accessibility in Ningbo (China) and its matching with different levels of residential areas. We present a case study in Ningbo, and discuss its implications for PGS management. This study contains two elements: (a) Compare the current and initial PGS accessibility of each community to accurately identify the communities with PGS vacancies. (b) Analyze and discuss the association between community accessibility and residential house prices. Compare the PGS coverage ratios of communities at different levels to determine the equity of PGS planning in Ningbo. We found that the level of PGS allocation in the central area of Ningbo is high. Obviously, high-value clusters are formed in Sanjiangkou, Zhenhai New Town, Southern and Eastern Yinzhou. The accessibility level in the middle area of Yinzhou is low, and there are super high accessibility residential communities in the outer city area. There is an exact period of green space vacancy in the middle and the outer area. The residential areas with ultra-high accessibility did not configure PGS services at the beginning of their construction. There is no noticeable difference in PGS accessibility of residential communities of different levels at present, but 149 low- and middle-income residential communities lack green space service when the construction was completed. High-end residential communities have priority on enjoying park green space services. Our study suggests that PGS accessibility should be studied temporally and spatially for each residential community. The Ningbo government should strengthen the balanced construction of green space in parks and guarantee green space services for low-end residential communities to improve green space equity.
Assuntos
Planejamento de Cidades , Parques Recreativos , China , CidadesRESUMO
Major depression is becoming one of the most prevalent forms of psychiatric disorders. However, the mechanisms of major depression are still not well-understood. Most antidepressants are only effective in some patients and produce some serious side effects. Animal models of depression are therefore essential to unravel the mechanisms of depression and to develop novel therapeutic strategies. Our previous studies showed that Abelson helper integration site-1 (Ahi1) deficiency causes depression-like behaviors in mice. In this study, we characterized the biochemical and behavioral changes in Ahi1 knockout (KO) mice. In Ahi1 KO mice, neurotransmitters including serotonin and dopamine were significantly decreased in different brain regions. However, glutamate and GABA levels were not affected by Ahi1 deficiency. The antidepressant imipramine attenuated depressive behaviors and partially restored brain serotonin level in Ahi1 KO mice. Our findings suggest that Ahi1 KO mice can be used for studying the mechanisms of depression and screening therapeutic targets.
Assuntos
Comportamento Animal , Transtorno Depressivo Maior/genética , Neurotransmissores/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Adaptadoras de Transporte Vesicular , Animais , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/patologia , Dopamina/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Imipramina/administração & dosagem , Camundongos , Camundongos Knockout , Neurotransmissores/metabolismo , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
Apelin is an endogenous ligand of G protein-coupled receptor-apelin and angiotensin-1-like receptor (APJ). The biological effects of apelin-APJ system are reported in multiple systems including cardiovascular, endocrinal, and gastrointestinal system. Previous studies had shown that apelin-13 is a potential protective agent on cardiac ischemia; however, the role of apelin in the central nervous system remained unknown. In this study, we investigated therapeutic effects of apelin-36, a long form of apelin, in ischemic brain injury models. We found that apelin-36 reduced cerebral infarct volume in the middle cerebral artery occlusion (MCAO) model and the neonatal hypoxic/ischemic (H/I) injury model. Apelin-36 improved neurological deficits in the MCAO model and promoted long-term functional recovery after H/I brain injury. We further explored the protective mechanisms of apelin-36 on H/I brain injury. We clearly demonstrated that apelin-36 significantly reduced the levels of cleaved caspase-3 and Bax, two well-established apoptotic markers after H/I injury, indicating the anti-apoptotic activity of apelin-36 in ischemic injury. Since apelin-36 increased the level of phosphorylated Akt after H/I injury, we treated neonates with a specific PI3K inhibitor LY294002. We found that LY294002 decreased the phosphorylated Akt level and attenuated protective effects of apelin-36 on apoptosis. These suggested that the PI3K/Akt pathway was at least in part involved in the anti-apoptotic mechanisms of apelin-36. Our findings demonstrated that apelin-36 was a promising therapeutic agent on the treatment of ischemic brain injury.
Assuntos
Isquemia Encefálica/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Fármacos Neuroprotetores/farmacologia , Proteína Oncogênica v-akt/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Adipocinas , Animais , Animais Recém-Nascidos , Apelina , Infarto da Artéria Cerebral Média/patologia , Injeções Intraventriculares , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/prevenção & controle , Transdução de Sinais/efeitos dos fármacosRESUMO
A method for the simultaneous determination of glyoxalate and oxalate by capillary zone electrophoresis (CZE) was developed. The influences of type, concentration and pH of the running buffer, and the applied voltage on separation were investigated. Glyoxalate and oxalate were separated within 11 min under the conditions of 20 mmol/L borax-5.5 mmol/L potassium hydrogen phthalate (pH 9.0), applied voltage of 20 kV, and detected wavelength of 212 nm. The calibration curves of glyoxalate and oxalate showed good linearity in the ranges of 0.8 -20 g/L and 1.2-20 g/L, respectively. The correlation coefficients were 0.999 3 and 0.997 5, respectively. The limits of detection for glyoxalate and oxalate were 0.2 and 0.4 g/L (S/N = 3), respectively. The average recoveries at three spiked levels were 98.3%-102.5% with acceptable relative standard deviations of 0.35%-0.61%. This method is simple, low cost and high performance. The method was successfully used for the determination of glyoxalate and oxalate in real samples, and the assay results were satisfactory.
Assuntos
Eletroforese Capilar/métodos , Glioxilatos/análise , Oxalatos/análise , Sensibilidade e EspecificidadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Suanzaorenhehuan Formula (SHF) is a Chinese herbal formula for the treatment of depression-like disorders. It contains four herbs: Semen Ziziphi spinosae, Cortex Albiziae, Radix Paeoniae Alba and Semen Platycladi. The present study is to investigate the antidepressant-like effect of the ethanolic extract of SHF and its possible mechanisms. MATERIALS AND METHODS: Mouse models of depression including the tail suspension test (TST), forced swimming test (FST) and chronic unpredicted mild stress (CUMS) were used to evaluate the effects of SHF extract. The mechanisms were examined by measuring monoamine neurotransmitters in mice hippocampus and frontal cortex, testing monoamine oxidase enzyme (MAO) activities in brain of CUMS-exposed mice. RESULTS: After one-week treatment, SHF extract (50, 100 and 200mg/kg) induced a significant decrease on immobility time in TST. After two-week treatment, SHF extract (50, 100 and 200mg/kg) led to a reduction in the immobility period in TST and FST. The 5-HT levels in mice hippocampus were increased only after 200mg/kg SHF extract treatment. The noradrenaline (NE) levels were increased after 200mg/kg SHF extract treatment in mice hippocampus and frontal cortex. SHF extract (50, 100 and 200mg/kg) significantly inhibited monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) after 21-day CUMS exposure. CONCLUSION: These findings demonstrated that ethanolic SHF extract produced an antidepressant-like effect and the mechanism of action involves the serotonergic, noradrenergic and monoamine oxidase enzyme systems although underlying mechanism still remains to be further elucidated.
Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Etanol/química , Solventes/química , Animais , Antidepressivos/química , Comportamento Animal/efeitos dos fármacos , Fracionamento Químico , Cicloexanóis/farmacologia , Depressão/metabolismo , Depressão/psicologia , Modelos Animais de Doenças , Dopamina , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Monoaminoxidase/metabolismo , Atividade Motora/efeitos dos fármacos , Norepinefrina/metabolismo , Fitoterapia , Plantas Medicinais , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Serotonina/metabolismo , Fatores de Tempo , Cloridrato de VenlafaxinaRESUMO
By using RS and GIS techniques, the spatiotemporal changes of wetlands in Hangzhou Bay Industrial Belt, one of the most developed zones in Zhejiang Province, from 1990 to 2005 were studied. There was a frequent conversion between the wetlands and other land use types and between the wetlands themselves, mainly manifested in the conversion between wetland and farmland, and from wetland to construction land and from tidal flat to aquiculture area. The comparative advantage of other land use types and the policy of cultivated land's requisition-compensation balance decided the inherent mechanisms of these spatiotemporal changes. Driven by the aquaculture's comparative advantage to traditional agriculture, large areas of inland farmland and of the tidal flat along the coast of Hangzhou Bay were reclaimed into aquiculture area, and the rapid expansion of construction land, limited land resources, and the implement of cultivated land's requisition-compensation balance policy induced the wetlands being occupied.