Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 304
Filter
1.
Saúde Redes ; 8(Supl. 2): 59-67, 20221119.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1411482

ABSTRACT

A saúde mental, especificamente no tratamento para o uso abusivo de psicoativos, exigem conhecimentos, habilidades e atitudes de enfermeiros a realizarem suas tarefas com responsabilidade, qualidade e gestão de tempo. Este estudo teve como objetivo relatar a construção de um instrumento para a facilitar o planejamento de plantão de um enfermeiro em saúde mental em um serviço de um Caps AD III. Para tanto o trabalho segue os pressupostos metodológicos da pesquisa de relato de experiência. Como resultado, o presente relato produziu o instrumento de planejamento de plantão, juntamente com os benefícios e a limitações de sua implementação no serviço. A prática de enfermagem em saúde mental pôde ser facilitada pela utilização de um instrumento de planejamento de plantão. Possibilitando a gestão de tempo e estratificação das tarefas em urgentes e importantes.

2.
Article in English | LILACS-Express | LILACS | ID: biblio-1406878

ABSTRACT

ABSTRACT Human Adenovirus 36 (HAdV-36) has been related to diverse effects on metabolism and may attenuate the lipid accumulation in kidneys with increased adiposity. Some of these effects would be related to viral persistence. However, until now, a model of persistent in vitro infection by HAdV-36 is unknown. In this study, we examined the cells of the Vero lineage to explore their permissiveness to long-term HAdV-36 infection. HAdV-36 was productively replicated in Vero cells and maintained long-term infection for up to 35 cell passages. A subculture was obtained from the cells that survived the primary infection at a low MOI (0.5). The production of the extracellular infectious virus with titers ranging from 104 to 106 TCID50/mL and DNA-bearing cells was detected. In long-term infected cells, the intracellular distribution of viral antigen was demonstrated by performing immunolocalization (IFI) and expression of cell-viral antigen in 50% of cells by flow cytometry, using anti-HAdV-36 hyperimmune rabbit serum. Furthermore, E1a and E4orf1 genes in long-term infected passages showed a decreasing trend. Our preliminary results reveal that renal epithelial monkey cells are permissive for the productive infection of HAdV-36. Vero cell culture long-term infection might be a promising model for addressing the fundamental aspects of the HAdV-36 biology that cannot reveal broadly-used cultures, which do not maintain long-term infection in primary or transformed cells.

3.
Chinese Journal of Biotechnology ; (12): 1086-1095, 2022.
Article in Chinese | WPRIM | ID: wpr-927765

ABSTRACT

ERα-36 is a novel subtype of estrogen receptor α which promotes tumor cell proliferation, invasion and drug resistance, and it serves as a therapeutic target. However, only small-molecule compounds targeting ERα-36 are under development as anticancer drugs at present. Gene therapy approach targeting ERα-36 can be explored using recombinant adenovirus armed with decoy receptor. The recombinant shuttle plasmid pDC316-Ig κ-ERα-36-Fc-GFP was constructed via genetic engineering to express an Ig κ-signaling peptide-leading secretory recombinant fusion protein ERα-36-Fc. The recombinant adenovirus Ad-ERα-36-Fc-GFP was subsequently packaged, characterized and amplified using AdMaxTM adenovirus packaging system. The expression of fusion protein and functional outcome of Ad-ERα-36-Fc-GFP transduction were further analyzed with triple-negative breast cancer MDA-MB-231 cells. Results showed that the recombinant adenovirus Ad-ERα-36-Fc-GFP was successfully generated. The virus effectively infected MDA-MB-231 cells which resulted in expression and secretion of the recombinant fusion protein ERα-36-Fc, leading to significant inhibition of EGFR/ERK signaling pathway. Preparation of the recombinant adenovirus Ad-ERα-36-Fc-GFP provides a basis for further investigation on cancer gene therapy targeting ERα-36.


Subject(s)
Adenoviridae/genetics , Cell Proliferation , Estrogen Receptor alpha/metabolism , Recombinant Proteins , Transfection
4.
Article in Chinese | WPRIM | ID: wpr-942322

ABSTRACT

ObjectiveTo investigate the effects of 4 weeks of aerobic exercise combined with traditional Chinese medicine (TCM) on the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway and related apoptotic proteins in AD rats, and to explore its mechanism of action in improving cognitive function of AD rats. MethodFifty male SD rats were randomly divided into Sham group, exercise (EX) group, Alzheimer's disease (AD) group (model), TCM group (Dabuyuan Jian), and EX+TCM group, 10 in each group. Aβ25-35 oligomer solution was injected into the hippocampal region to establish the AD rat model, and the EX group underwent 6 days/week of running table training. The TCM group was given Dabuyuan Jian (5.36 g∙kg-1) by gavage, and the EX+TCM group received running table training combined with intragastric administration of Dabuyuan Jian. An equal volume of purified water was given to the Sham, AD, and EX groups by gavage. The rats' learning memory was evaluated by Morris water maze. The morphological changes and ultrastructural changes of hippocampal neurons were observed by hematoxylin-eosin (HE) staining and transmission electron microscopy, respectively. Western blot was performed to detect the protein expression levels of Akt, p-Akt, GSK-3β, p-GSK-3β, β-catenin, Bcl-2, Bax, and cleaved Caspase-3 in the hippocampus of rats. ResultCompared with the Sham group, the AD group showed an increase in escape latency and total swimming distance, and a decrease in the residence time in the target quadrant (P<0.01), with loose and disorganized arrangement of hippocampal pyramidal cells, a decrease in density, myelin-like changes in hippocampal ultrastructure, and a blurring of mitochondrial swelling. In addition, the expression of Bcl-2, p-Akt, p-GSK-3β and β-catenin was down-regulated (P<0.05, P<0.01) while the expression of cleaved Caspase-3 was up-regulated (P<0.05). Compared with the conditions in the AD group, the escape latency and swimming distance were reduced in the EX, TCM, and EX+TCM groups, while the residence time in the target quadrant was increased (P<0.05,P<0.01), with regularly arranged pyramidal cells, elevated number of cells, and reduced myelin-like changes and improved mitochondrial swelling as seen by transmission electron microscopy. Moreover, the expression of Bcl-2, p-Akt and p-GSK-3β was up-regulated, while the expression of cleaved Caspase-3 was down-regulated(P<0.05,P<0.01). The EX+TCM group had increased level of β-catenin while the EX and TCM groups were not statistically significant compared with the AD group. Compared with the EX+TCM group, the EX and TCM groups had increased escape latency and swimming distance and decreased residence time in the target quadrant(P<0.05,P<0.01), with loosely arranged pyramidal cells and reduced synaptic integrity under transmission electron microscopy(P<0.01). Furthermore, the levels of Bcl-2, p-Akt, p-GSK-3β and β-catenin were lowered (P<0.05,P<0.01)while the level of cleaved Caspase-3 was elevated(P<0.05). ConclusionAerobic exercise combined with Dabuyuan Jian could improve the cognitive dysfunction of AD rats, and the mechanism might be related to the elevated expression of key proteins in the PI3K/Akt/GSK-3β signaling pathway. The combined use was better than the use of exercise or drugs alone.

5.
Article in Chinese | WPRIM | ID: wpr-940755

ABSTRACT

ObjectiveTo investigate the protective effect of Liuwei Dihuangwan on neurovascular injury in SAMP8 mice. MethodThe Alzheimer's disease (AD) model with insufficiency of kidney essence was induced in 75 SAMP8 mice aging 6 months. The model mice were divided into model group, positive control group (donepezil hydrochloride, 0.747 mg·kg-1·d-1), and high-, medium-, and low-dose Liuwei Dihuangwan groups (2.700, 1.350, 0.675 g·kg-1·d-1), with 15 mice in each group. Fifteen SAMR1 mice were assigned to a normal control group. All mice were administered continuously for 2 months. The spatial memory of mice was tested by the Morris water maze. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the hippocampus and cortex of brain tissues. The immunohistochemical method (IHC) was used to detect the deposition of amyloid β-protein (Aβ) and the expression of von Willebrand factor (vWF) and CD34 in the hippocampus and cortex of brain tissues. Electron microscopy was used to observe the ultrastructural changes in cerebral microvessels. Western blot was used to detect the protein expression levels of the receptor of advanced glycation endproduct (RAGE), low-density lipoprotein receptor-related protein 1 (LRP1), vascular endothelial growth factor A (VEGF-A), and P-selection in the hippocampus and cortex of brain tissues. ResultCompared with the normal control group, the model group showed prolonged escape latency and swimming distance (P<0.01), increased number of glial cells, decreased number of nerve cells, blurred tight junctions or enlarged gap of the brain microvascular endothelial cells, severely injured membrane structure, swollen mitochondria of endothelial cells, ruptured membrane, massive dissolution in cristae, increased protein expression of Aβ and vWF in the hippocampus and cortex (P<0.01), reduced protein expression of CD34 (P<0.05), elevated protein expression of RAGE and P-selection in the cortex (P<0.01), and decreased protein expression level of LRP1 and VEGF-A (P<0.01). Compared with the model group, the Liuwei Dihuangwan groups showed shortened escape latency and swimming distance (P<0.05), reduced number of glial cells in the cortex and hippocampus, increased number of microvessels in the cortex, clear double-layer membrane structure in tight junctions between the microvascular endothelial cells, increased number of mitochondria with intact membrane and recovered mitochondrial cristae, decreased protein expression of Aβ, vWF, RAGE, and P-selection in the hippocampus and cortex (P<0.05), and increased protein expression of CD34, LRP1, and VEGF-A (P<0.05). ConclusionLiuwei Dihuangwan can regulate Aβ metabolism through the RAGE/LRP1 receptor system and promote cerebral microvascular angiogenesis by inhibiting vWF expression and increasing VEGF-A and CD34, thereby improving cerebral microvascular injury in SAMP8 mice.

6.
Article in Chinese | WPRIM | ID: wpr-940635

ABSTRACT

ObjectiveTo explore the possible mechanism of dried fruiting bodies of Fomes officinalis (FOA) against Alzheimer's disease (AD) based on network pharmacology and experimental verification. MethodThe effective components of FOA were retrieved from a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) and previous reports. The targets of the components were searched from PharmMapper and TargetNet, and the targets related to AD from Gene Expression Omnibus (GEO), DrugBank, among other databases. Thereby, the common targets of FOA and AD were obtained, and the protein-protein interaction (PPI) network and component-target network were established based on STRING and Cytoscape 3.7.1, followed by the topology analysis of the networks, and Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the common targets. The results were verified by the molecular docking and the in vitro cell experiment. ResultA total of 24 candidate components and 242 predicted targets of FOA, and 96 common targets of FOA and AD were screened out. The key components included [2-(1-carboxyhexadecylamino)-2-aminosuccinic acid], 3-keto-dehydrosulfurenic acid, and eburicoic acid, and the active targets were albumin (ALB), acetylcholinesterase (AChE), estrogen receptor 1 (ESR1), cysteine aspartate-specific protease-3 (Caspase-3), and beta-secretase1 (BACE1). The common targets were involved in 392 GO terms, and the key terms were the β-amyloid metabolic process and cholinesterase activity. A total of 77 KEGG pathways were obtained, which mainly included estrogen signaling pathway, cholinergic synapse, and AD. The results of molecular docking showed that 7 components of FOA had high binding affinity to amyloid precursor protein (APP), BACE1, AChE, and Caspase-3. The cell survival rate rose (P<0.01) and the mRNA and protein expression of APP, BACE1, AChE, and Caspase-3 reduced in FOA groups in a dose-dependent manner compared with those in the model group (P<0.05). ConclusionThis study reveals for the first time that FOA has multi-component, multi-target, and multi-pathway characteristics in the treatment of AD, which serves as a reference for further explaining the mechanism of FOA against AD.

7.
Article in Chinese | WPRIM | ID: wpr-940513

ABSTRACT

ObjectiveTo explore the pharmacodynamic effect of gramine on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice and its potential mechanism. MethodThe mice were divided into the normal control group, model group, dexamethasone (0.05 g·kg-1) group, and high- and low-dose (0.12,0.06 g·kg-1) gramine groups. Mice in all groups except for the normal control group were stimulated with DNCB, followed by medication 13 d later. The changes in skin lesions were then observed, and the skin thickness, moisture content, and transepidermal water loss (TWEL) in each group were measured. The pathological changes in skin lesions were observed by hematoxylin-eosin (HE) staining, and the effects of drugs on CD4+/CD8+T-cell ratio in the spleen were detected by flow cytometry. The levels of immunoglobulin E (IgE), interleukin (IL)-4, and IL-6 in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the changes in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (CRE) by microplate method. The mRNA expression levels of inflammatory cytokines γ-interferon(IFN-γ), IL-13, IL-17, IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in skin lesions were assayed by real-time polymerase chain reaction (Real-time PCR), and the protein expression levels of nuclear transcription factor -κB (NF-κB) and NF-κB inhibitory protein α (IκBα) in skin lesions by Western blot. ResultCompared with the normal control group, the model group showed skin edema, erythema, scab, scratch, and lymphocyte and neutrophil infiltration, decreased skin moisture content, as well as increased skin thickness, TWEL (P<0.01), spleen index, CD4+/CD8+ T-cell ratio in the spleen (P<0.05), mRNA expression of IFN-γ, IL-13, IL-17, IL-1β, IL-6, and TNF-α in the skin lesions (P<0.05), serum contents of IgE, IL-4, and IL-6 (P<0.05), and protein expression of IκBα and NF-κB in skin lesions (P<0.05). Compared with the model group, dexamethasone and gramine at different doses alleviated skin erythema, scale, scab, and inflammatory cell infiltration, elevated skin moisture content, inhibited skin thickening and TWEL, and decreased spleen index, CD4+/CD8+T-cell ratio in the spleen, mRNA expression of inflammatory factors in the skin lesions, serum contents of IgE and inflammatory factors, and protein expression of IκBα and NF-κB in skin lesions, especially in the dexamethasone group and the high- dose gramine group(P<0.05,P<0.01). ConclusionGramine can inhibit the expression of related inflammatory factors and regulate the immune function of AD mice via the IκBα/NF-κB pathway, enabling it become a potential drug for treating AD.

8.
Article in Chinese | WPRIM | ID: wpr-940512

ABSTRACT

ObjectiveTo explore the effect of Qishengwan on ileal flora during its treatment of Alzheimer's disease (AD) under the guidance of the theory of "interior-exterior relationship between heart and small intestine". MethodThe AD model was established by bilateral intraventricular injection of β-amyloid 1-42 (Aβ1-42). The rats were then randomly divided into the blank group, sham-operated group, model group, low-, medium-, and high-dose (5.6, 11.2,22.4 g·kg-1·d-1) Qishengwan groups, and donepezil (0.46 mg·kg-1·d-1) group. After medication for 28 successive days, the spatial memory ability of rats was observed in water maze test, and the levels of Aβ1-42, nuclear transcription factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the hippocampus were analyzed by enzyme-linked immunosorbent assay (ELISA). Additionally, the contents of the ileum were collected and subjected to 16SrRNA-sequencing analysis for figuring out the changes in ileal flora. ResultCompared with the blank group and sham-operated group, the model group exhibited significantly reduced stay time in the target quadrant and number of target quadrant and platform crossings (P<0.05, P<0.01) and elevated Aβ1-42 content in the hippocampus (P<0.01) and central inflammatory factors NF-κB, TNF-α, and IL-6 (P<0.05, P<0.01). Compared with the model group, Qishengwan at each dose significantly alleviated the impaired spatial memory function (P<0.05, P<0.01), improved the deposition of Aβ1-42 in the hippocampus of rats (P<0.05, P<0.01), and reduced the expression of central nervous system inflammatory factors (P<0.05, P<0.01), thus exerting a good therapeutic effect on AD rats. The 16SrRNA-sequencing analysis results showed that the structure of the ileal flora in the model group was significantly separated from those in the blank group and sham-operated group. The abundance of Lachnospiraceae NK4A136 group was significantly increased (P<0.01), while that of Escherichia-Shigella was reduced (P<0.05, P<0.01). Qishengwan at each dose significantly changed the ileal flora structure and regulated the relative abundance of Lachnospiraceae NK4A136 group, Escherichia-Shigella, and Ruminococcaceae. ConclusionQishengwan has a positive therapeutic effect on AD. It can significantly enhance the memory and cognitive abilities in AD rats, which may be related to its regulation of the structure of rat ileal flora and the relative abundance of Lachnospiraceae NK4A136 group, Escherichia-Shigella, and Ruminococcaceae, the attenuation of the central neuroinflammatory response, and the reduction of central Aβ1-42 deposition.

9.
Article in Chinese | WPRIM | ID: wpr-940509

ABSTRACT

Atopic dermatitis (AD) is a chronic, recurrent and inflammatory skin disease. Modern medical research suggests that AD is related to immune function, genes, skin barrier and other factors, while the specific etiology and pathogenesis remains unclear. The disease has a long course and is prone to reoccur, which seriously affects people’s production and life. Steroids, antihistamines and immunosuppressants are commonly used western medicines for the treatment of AD, which, however, will cause adverse reactions after long-term application. Traditional Chinese medicine (TCM) has a long history, good therapeutic effect and rich clinical experience in the prevention and treatment of AD, and the research on the treatment of AD with TCM has been intensifying. Centering on the theory of TCM, we systematically summarized the research progress related to AD, discussed the etiology and pathogenesis of AD, and summarized the TCM syndrome differentiation of AD from the aspects of eight principles, etiology, Qi-blood-body fluid, zang-fu organs, six meridians, defense-Qi-nutrient-blood and triple energizer. According to the etiology and pathogenesis of AD, we proposed the therapeutic regimens corresponding to the type and stage of the disease. Considering the research progress achieved in the recent years in the prevention and treatment of AD by TCM and the modern pharmacological research on Chinese medicinal materials, we reviewed the classic famous prescriptions, self-made prescriptions and Chinese patent medicines, and expounded the mechanisms of single Chinese medicinal materials in the treatment of AD at the molecular level. The TCM external therapies such as wet compress, medicated bath, gel and ointment are safe and effective. Acupuncture and moxibustion play a role in the prevention and treatment of AD, which is worthy of promotion in clinical practice, and the syndrome differentiation methods of Qi-blood-body fluid and triple energizer are novel in the treatment of this disease. TCM, characterized by diverse therapeutic methods and good clinical efficacy, is worthy of promotion in the treatment of AD, which will contribute to the development of TCM in China.

10.
Article in Chinese | WPRIM | ID: wpr-940498

ABSTRACT

ObjectiveTo investigate the potential mechanism of Xiao Chaihutang (XCHT) in the treatment of Alzheimer's disease (AD) based on network pharmacology and bioinformatics. MethodThe active components of XCHT and corresponding targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the differentially expressed genes related to AD were searched from Gene Expression Omnibus (GEO). Thereby, the common targets of XCHT and AD were yielded, followed by Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the common targets. The component-target network and protein–protein interaction (PPI) network were constructed. Furthermore, amyloid β-protein (Aβ)1-40 was used to induce AD in PC12 cells and then the AD cells were intervened with XCHT. Afterward, cell viability was detected by Cell Counting Kit-8 (CCK-8) assay and cell morphology was observed based on 4',6-diamidino-2-phenylindole (DAPI) staining. Cell membrane potential was determined and apoptosis was detected by flow cytometry, and cellular immunofluorescence detects the expression of B-cell lymphoma-2 (Bcl-2)/Bcl-2-related X protein (Bax). Moreover, immunofluorescence assay was performed. ResultA total of 190 active components and 41 anti-AD targets of XCHT were screened out. The key components included mairin, quercetin, berberine, protoporphyrin, 24-ethylcholest-4-en-3-one, and β-D-ribofuranoside, and the core targets were sigma non-opioid intracellular receptor 1 (SIGMAR1), checkpoint kinase 1 (CHEK1), protein tyrosine phosphatase non-receptor type 6 (PTPN6), protein kinase C(PRKCH), inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB), cathepsin D (CTSD), cysteine aspartate protease-3 (Caspase-3), Bax, and Bcl-2-like protein 1 (Bcl-2L1). The anti-AD targets of XCHT were involved in 302 GO terms (P < 0.05), particularly the regulation of neuronal cell apoptosis, and 73 KEGG pathways (P<0.05). The major pathways and biological processes included the apoptosis pathway, virus infection pathway, lipid and atherosclerosis pathway, and cancer-related pathways. In the in vitro experiment, the model group demonstrated the decrease in cell survival rate (P<0.05), increase in apoptosis rate (P<0.05), and down-regulation of mitochondrial membrane potential and Bcl-2/Bax ratio compared with the blank control. Compared with the model group, XCFT group showed the increase in cell survival rate (P<0.05), decrease in apoptosis rate (P<0.05), and up-regulation of mitochondrial membrane potential and Bcl-2/Bax ratio. ConclusionBased on network pharmacology, this study reveals the multi-component, multi-target, and multi-pathway characteristics of XCHT in the treatment of AD, laying a foundation for further research on the material basis and mechanism of this prescription.

11.
Article in Chinese | WPRIM | ID: wpr-940409

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disease. With the acceleration of aging process, the number of AD patients increases year by year. This threatens the health and even life of patients, and causes heavy economic burden and mental pressure to patients, families and society. In traditional Chinese medicine (TCM), AD belongs to the category of dementia, and tonifying kidney is the main treatment. Based on the basic theory of TCM and combined with clinical manifestations of AD, AD is closely correlated with liver and spleen. Therefore, "simultaneous regulation of three Yin" of liver, spleen and kidney will be an important way for the prevention and treatment of AD. Hei Xiaoyaosan, a representative prescription of "simultaneous regulation of three Yin" of liver, spleen and kidney, has theoretical, experimental and clinical basis in preventing and treating AD. Modern studies have shown that neurofibrillary tangle formed by tau hyperphosphorylation is a main pathological feature of AD, and trimethylamine oxide (TMAO) is closely related to tau hyperphosphorylation. Therefore, regulating TMAO metabolism to inhibit tau hyperphosphorylation is a new target for the prevention and treatment of AD. On the basis of the above theory and previous studies, this paper put forward the hypothesis that Hei Xiaoyaosan regulates the trimethylamine(TMA)/heparin monooxygenase 3(FMO3)/TMAO metabolic pathway of intestinal flora through "simultaneous regulation of three Yin" of liver, spleen and kidney, and then inhibits tau hyperphosphorylation in brain hippocampus, thereby protecting nerve cells, improving learning and memory, and preventing AD. This paper explored the role and mechanism of Hei Xiaoyaosan in the prevention and treatment of AD from the perspective of inhibiting tau hyperphosphorylation by regulating the TMA/FMO3/TMAO metabolic pathway of intestinal flora, which provided new ideas and strategies for in-depth study of Hei Xiaoyaosan in the prevention and treatment of AD.

12.
Article in Chinese | WPRIM | ID: wpr-940283

ABSTRACT

ObjectiveTo observe the effect of Linggui Zhugantang (LG) on the blood-brain barrier (BBB) model of Alzheimer's disease (AD) in vitro and to explore the mechanism of LG in repairing the BBB injury in AD. MethodA total of 50 male SPF rats were randomized into five groups: high-dose (4.8 g·kg-1), medium-dose (2.4 g·kg-1), and low-dose (1.2 g·kg-1) LG groups, western medicine (0.5 g·kg-1 donepezil hydrochloride) group, and normal group (normal saline of equivalent volume). They received (ig) corresponding drugs twice a day for 7 d. Drug-containing serum was respectively collected from the abdominal aorta 1 h after the last administration. The BBB injury of AD in vitro was induced with the cell co-culture method, and 6 groups were designed: normal group, model group, high-, medium-, and low-dose LG groups, and western medicine group. The model group was added with 100 μL amyloid β1-42 (Aβ1-42, final concentration: 5 μmol·L-1), and high-dose, medium-dose, and low-dose LG groups and the western medicine group were added with corresponding 10% drug-containing serum in addition to the 100 μL Aβ1-42 (final concentration: 5 μmol·L-1). Cell survival rate was detected by methyl thiazolyl tetrazolium (MTT) assay, expression of BBB-related skeleton proteins (claudin-5, ZO-1, occludin), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) by Western blot, and content of inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay (ELISA). BBB Aβ transporter low-density lipoprotein receptor-related protein 1 (LRP-1) and advanced glycation end product receptor (RAGE) at different time points in high-dose, medium-dose, and low-dose LG groups were determined by Real-time PCR and Western blot. ResultCell survival rate of the model group was lower than that of the normal group (P<0.05) and the survival rates of the western medicine group and high-dose LG group was higher than that in the model group (P<0.05). The skeleton proteins were down-regulated and MMP-2 and MMP-9 were up-regulated in the model group compared with those in the normal group (P<0.05). The expression of skeleton proteins was higher (P<0.05) and that of MMP-2 and MMP-9 was lower (P<0.05) in the western medicine group and high-dose LG group than in the model group. Compared with the model group, only the medium-dose LG group showed the up-regulation (P<0.05) of claudin-5 (P<0.05) and the decrease (P<0.05) of MMP-2. IL-1β, IL-6, and TNF-α in the model group were up-regulated (P<0.05) compared with those in the normal group, and those inflammatory factors in the western medicine group and high-dose and medium-dose LG groups were lower (P<0.05) than those in the model group. LRP-1 expression was up-regulated and RAGE expression was down-regulated at 3 h compared with those at 0 h (P<0.05), while the expression of the two became stable at 6, 12, 24, 36 h. At 3 h, LRP-1 expression was down-regulated and RAGE expression was up-regulated in model group compared with those in the normal group at 3 h (P<0.05). Moreover, the LRP-1 content was higher and RAGE content was lower in the western medicine group and high-dose LG group than in the model group. ConclusionLG can repair the BBB injury in vitro by inhibiting the expression of inflammatory factors and MMP-2, MMP-9, promoting the expression of skeletal proteins, and regulating the balance of transporters.

13.
Article in Chinese | WPRIM | ID: wpr-929824

ABSTRACT

Vitamin AD is an essential nutrient in human, which can maintain the normal function of vision, immune system, respiratory tract, gastrointestinal epithelium and nervous system.Preterm infants are prone to vitamin AD deficiency due to low prenatal storage, low food intake, high energy metabolism, et al.Studies have shown that early supplementation of vitamin AD can promote the growth and development of preterm infants.This paper summarizes recent advances of vitamin AD supplementation in the improvement of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, brain injury and metabolic bone diseases of prematurity.The result has showed that vitamin AD supplementation within 1 week after birth could improve the occurrence of complications in preterm infants, which could provide new ideas and methods for reducing the major complications of preterm infants.

14.
Acta Pharmaceutica Sinica B ; (6): 1019-1040, 2022.
Article in English | WPRIM | ID: wpr-929367

ABSTRACT

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by memory loss and cognitive dysfunction. The accumulation of misfolded protein aggregates including amyloid beta (Aβ) peptides and microtubule associated protein tau (MAPT/tau) in neuronal cells are hallmarks of AD. So far, the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited. Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes. Recently, there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis. Interestingly, the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD. Here, we first summarize the recent genetic, pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD. We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins, Aβ and MAPT/tau, in AD. Finally, we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials. Overall, this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment.

15.
Acta Pharmaceutica Sinica B ; (6): 511-531, 2022.
Article in English | WPRIM | ID: wpr-929312

ABSTRACT

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.

16.
Acta Pharmaceutica Sinica B ; (6): 483-495, 2022.
Article in English | WPRIM | ID: wpr-929310

ABSTRACT

Alzheimer's disease (AD), the most prominent form of dementia in the elderly, has no cure. Strategies focused on the reduction of amyloid beta or hyperphosphorylated Tau protein have largely failed in clinical trials. Novel therapeutic targets and strategies are urgently needed. Emerging data suggest that in response to environmental stress, mitochondria initiate an integrated stress response (ISR) shown to be beneficial for healthy aging and neuroprotection. Here, we review data that implicate mitochondrial electron transport complexes involved in oxidative phosphorylation as a hub for small molecule-targeted therapeutics that could induce beneficial mitochondrial ISR. Specifically, partial inhibition of mitochondrial complex I has been exploited as a novel strategy for multiple human conditions, including AD, with several small molecules being tested in clinical trials. We discuss current understanding of the molecular mechanisms involved in this counterintuitive approach. Since this strategy has also been shown to enhance health and life span, the development of safe and efficacious complex I inhibitors could promote healthy aging, delaying the onset of age-related neurodegenerative diseases.

17.
Article in Chinese | WPRIM | ID: wpr-906165

ABSTRACT

Alzheimer's disease (AD) is currently the most common neurodegenerative disorder characterized by insidious onset and slow progression, which has seriously endangered the physical and mental health of the elderly. It is therefore very important to carry out the early diagnosis and active prevention and treatment. Biomarkers are essential for its diagnosis. Looking for ideal biomarkers is helpful for early identification of this disease. The prevention and treatment of AD with traditional Chinese medicine (TCM) has always been a hot spot in scientific research due to good safety and small side effects. Proteomics is an advanced omics technology that enables the identification and characterization of proteins. Its high-throughput, dynamic, and comprehensive characteristics coincide with the concept of holism emphasized in TCM diagnosis and treatment, which makes proteomics suitable for identifying biomarkers with diagnostic potential, objectifying TCM syndrome differentiation and treatment, and developing new Chinese medicinal prescriptions for precise and targeted treatment. Although the proteomics technology is becoming increasingly mature, it still faces challenges in the diagnosis and treatment of AD. There exist such shortcomings as high heterogeneity and poor reproducibility of protein omics results, requirement for the combination with other advanced omics technologies, and high sequencing cost. In the future, the protein omics technology should be constantly updated and optimized to boost precision medicine, disease prevention, and drug research and development. This paper retrieved related articles from Pubmed, China National Knowledge Infrastructure (CNKI) and reviewed the application of proteomics in the early diagnosis of AD and its prevention and treatment with TCM in recent years, in order to provide reference for the in-depth study of AD diagnosis as well as its prevention and treatment with TCM.

18.
Article in Chinese | WPRIM | ID: wpr-906044

ABSTRACT

Objective:To investigate the neuroprotective effect of Danggui Shaoyaosan (DSS) in a rat model of amyloid-<italic>β</italic>-peptide<sub>1-42</sub> (A<italic>β</italic><sub>1-42</sub>)-induced Alzheimer's disease (AD) as well as its regulatory effect on NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase-1) signaling pathway. Method:The AD animal model was established via intracerebral injection of A<italic>β</italic><sub>1-42</sub> and treated with different concentrations of DSS after the division of rats into the sham operation group, model group, as well as the high-, medium-, and low-dose DSS groups. Morris water maze test was conducted to determine the learning and memory abilities of rats. The morphology and function of neurons were detected by hematoxylin-eosin (HE) staining and Golgi staining, followed by immunofluorescence co-localization of NLRP3 inflammasome activation. The mRNA expression levels of interleukin (IL)-1<italic>β</italic> and IL-18 were measured by Real-time polymerase chain reaction (Real-time PCR), and the protein expression levels of NLRP3, Caspase-1, and IL-1<italic>β </italic>were assayed by Western blot. Result:Compared with the sham operation group, the model group exhibited significantly decreased learning and memory abilities (<italic>P</italic><0.01), impaired neuronal morphology and function, up-regulated IL-1<italic>β</italic> and IL-18 mRNA expression, enhanced NLRP3 inflammasome activation, and elevated NLRP3, Caspase-1, and IL-1<italic>β</italic> protein expression (<italic>P</italic><0.01). Compared with the model group, DSS at both medium and high doses remarkably improved the learning and memory abilities of AD rats (<italic>P</italic><0.05, <italic>P</italic><0.01), restored neuronal morphology and function, down-regulated the mRNA expression levels of inflammatory factors IL-1<italic>β</italic> and IL-18, reduced the activation of NLRP3 inflammasomes, and lowered the protein expression levels of NLRP3, Caspase-1, and IL-1<italic>β</italic> (<italic>P</italic><0.01). Conclusion:DSS inhibits inflammasome activation and neuroinflammatory response possibly by regulating the NLRP3/Caspase-1 signaling pathway, thus exerting the neuroprotective effect.

19.
Acta Pharmaceutica Sinica B ; (6): 2306-2325, 2021.
Article in English | WPRIM | ID: wpr-888864

ABSTRACT

Blood-brain barrier (BBB) strictly controls matter exchange between blood and brain, and severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy of brain diseases. However, during the onset and progression of brain diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer's disease, Parkinson's disease, epilepsy, stroke, traumatic brain injury and brain tumor. The advances on optimization of small molecules for BBB crossing and non-systemic administration routes (

20.
Acta Pharmaceutica Sinica B ; (6): 1708-1720, 2021.
Article in English | WPRIM | ID: wpr-888831

ABSTRACT

Stroke is considered a leading cause of mortality and neurological disability, which puts a huge burden on individuals and the community. To date, effective therapy for stroke has been limited by its complex pathological mechanisms. Autophagy refers to an intracellular degrading process with the involvement of lysosomes. Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents. Increasing evidence support that autophagy protects neuronal cells from ischemic injury. However, under certain circumstances, autophagy activation induces cell death and aggravates ischemic brain injury. Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke. In the present work, we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.

SELECTION OF CITATIONS
SEARCH DETAIL