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1.
J Ethnopharmacol ; 283: 114678, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34563614

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiopogonis Radix, the commonly used traditional Chinese medicine in clinic for treating cardiovascular diseases, is returned to the stomach, lung and heart meridian. It is reported to nourish yin, moisten lung and is used to treat heart yin deficiency syndromes and asthenia of heart and lung, which indicated that Ophiopogonis Radix may have a protective effect on heart disorders. Atherosclerosisis is an important process in the development of cardiovascular diseases and abnormal lipid deposition induced macrophage foam cells is its crucial foundation. Our previous study showed the extract of Ophiopogonis Radix (EOR) ameliorates atherosclerosis in vitro. However, it may protect against cardiovascular diseases through inhibiting macrophage foam cell formation and its potential effective components and mechanisms are still unclear. AIM OF THE STUDY: Our study aimed to investigate the effect of Ophiopogonis Radix on macrophage foam cell formation and its potential active constituents and mechanisms. MATERIALS AND METHODS: Ox-LDL induced macrophage cells were employed to evaluate the effect of Ophiopogonis Radix on macrophage foam cell formation. Then the potential active constituents inhibited formation of macrophage foam cells were screened by biospecific cell extraction and its underlying mechanisms were also explored by Western blot. RESULTS: The extract of Ophiopogonis Radix was found to significantly inhibit macrophage foam cell formation, evidenced by the decrease of TG and TC and Oil Red O staining analysis in macrophage cells, which indicated that EOR reduced the formation of macrophage foam cells. At the same time, EOR was showed to increase antioxidant capacity in macrophage cells. After treatment with EOR, two potential active components interacted with macrophage foam cells specifically were identified to inhibit macrophage foam cell formation including methylophiopogonanone A and methylophiopogonanone B. Methylophiopogonanone A was then proved to decrease the expression of CD36, Lox-1 and SREBP2, increase the expression of ABCA1 obviously, while the expression of ABCG1 and SREBP1 had no changes. CONCLUSIONS: In our study, Ophiopogonis Radix was found to protect against atherosclerosis through suppressing ox-LDL induced macrophage foam cell formation and two potential compounds were identified by biospecific cell extraction including methylophiopogonanone A and methylophiopogonanone B. Moreover, methylophiopogonanone A was proved to inhibit foam cells through reducing uptake, synthesis and increasing efflux, which may provide guidance and reference for application of Ophiopogonis Radix and investigation of the effective components of TCMs.

2.
BMJ Glob Health ; 6(11)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34728477

RESUMO

This paper describes the lessons from scaling up a verbal autopsy (VA) intervention to improve data about causes of death according to a nine-domain framework: governance, design, operations, human resources, financing, infrastructure, logistics, information technologies and data quality assurance. We use experiences from China, Myanmar, Papua New Guinea, Philippines and Solomon Islands to explore how VA has been successfully implemented in different contexts, to guide other countries in their VA implementation. The governance structure for VA implementation comprised a multidisciplinary team of technical experts, implementers and staff at different levels within ministries. A staged approach to VA implementation involved scoping and mapping of death registration processes, followed by pretest and pilot phases which allowed for redesign before a phased scale-up. Existing health workforce in countries were trained to conduct the VA interviews as part of their routine role. Costs included training and compensation for the VA interviewers, information technology (IT) infrastructure costs, advocacy and dissemination, which were borne by the funding agency in early stages of implementation. The complexity of the necessary infrastructure, logistics and IT support required for VA increased with scale-up. Quality assurance was built into the different phases of the implementation. VA as a source of cause of death data for community deaths will be needed for some time. With the right technical and political support, countries can scale up this intervention to ensure ongoing collection of quality and timely information on community deaths for use in health planning and better monitoring of national and global health goals.

3.
J Cell Mol Med ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741385

RESUMO

Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can release a large number of exosomes which act as paracrine mediators in tumour-associated microenvironment. However, the role of MSC-derived exosomes in pathogenesis and progression of cancer cells especially osteosarcoma has not been thoroughly clarified until now. In this study, we established a co-culture model for human bone marrow-derived MSCs with osteosarcoma cells, then extraction of exosomes from induced MSCs and study the role of MSC-derived exosomes in the progression of osteosarcoma cell. The aim of this study was to address potential cell biological effects between MSCs and osteosarcoma cells. The results showed that MSC-derived exosomes can significantly promote osteosarcoma cells' proliferation and invasion. We also found that miR-21-5p was significantly over-expressed in MSCs and MSC-derived exosomes by quantitative real-time polymerase chain reaction (qRT-PCR), compared with human foetal osteoblastic cells hFOB1.19. MSC-derived exosomes transfected with miR-21-5p could significantly enhance the proliferation and invasion of osteosarcoma cells in vitro and in vivo. Bioinformatics analysis and dual-luciferase reporter gene assays validated the targeted relationship between exosomal miR-21-5p and PIK3R1; we further demonstrated that miR-21-5p-abundant exosomes derived human bone marrow MSCs could activate PI3K/Akt/mTOR pathway by suppressing PIK3R1 expression in osteosarcoma cells. In summary, our study provides new insights into the interaction between human bone marrow MSCs and osteosarcoma cells in tumour-associated microenvironment.

4.
J Alzheimers Dis ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34806605

RESUMO

BACKGROUND: Cognitive deficit is mainly clinical characteristic of Alzheimer's disease (AD). Recent reports showed adiponectin and its analogues could reverse cognitive impairments, lower amyloid-ß protein (Aß) deposition, and exert anti-inflammatory effects in different APP/PS1 AD model mice mainly exhibiting amyloid plaque pathology. However, the potential in vivo electrophysiological mechanism of adiponectin protecting against cognitive deficits in AD and the neuroprotective effects of adiponectin on 3xTg-AD mice including both plaque and tangle pathology are still unclear. OBJECTIVE: To observe the effects of adiponectin treatment on cognitive deficits in 3xTg-AD mice, investigate its potential in vivo electrophysiological mechanism, and testify its anti-inflammatory effects. METHODS: Barnes maze test, Morris water maze test, and fear conditioning test were used to evaluate the memory-ameliorating effects of adiponectin on 3xTg-AD mice. In vivo hippocampal electrophysiological recording was used to observe the change of basic synaptic transmission, long-term potentiation, and long-term depression. Immunohistochemistry staining and western blot were used to observe the activation of microglia and astroglia, and the expression levels of proinflammatory factors and anti-inflammtory factor IL-10. RESULTS: Adiponectin treatment could alleviate spatial memory and conditioned fear memory deficits observed in 3xTg-AD mice, improve in vivo LTP depression and LTD facilitation, inhibit overactivation of microglia and astroglia, decrease the expression of proinflammatory factors NF- κB and IL-1ß, and increase the expression level of IL-10 in the hippocampus of 3xTg-AD mice. CONCLUSION: Adiponectin could ameliorate cognitive deficits in 3xTg-AD mice through improving in vivo synaptic plasticity impairments and alleviating neuroinflammation in the hippocampus of 3xTg-AD mice.

5.
Eur Radiol ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34842959

RESUMO

OBJECTIVES: An accurate and rapid diagnosis is crucial for the appropriate treatment of pulmonary tuberculosis (TB). This study aims to develop an artificial intelligence (AI)-based fully automated CT image analysis system for detection, diagnosis, and burden quantification of pulmonary TB. METHODS: From December 2007 to September 2020, 892 chest CT scans from pathogen-confirmed TB patients were retrospectively included. A deep learning-based cascading framework was connected to create a processing pipeline. For training and validation of the model, 1921 lesions were manually labeled, classified according to six categories of critical imaging features, and visually scored regarding lesion involvement as the ground truth. A "TB score" was calculated based on a network-activation map to quantitively assess the disease burden. Independent testing datasets from two additional hospitals (dataset 2, n = 99; dataset 3, n = 86) and the NIH TB Portals (n = 171) were used to externally validate the performance of the AI model. RESULTS: CT scans of 526 participants (mean age, 48.5 ± 16.5 years; 206 women) were analyzed. The lung lesion detection subsystem yielded a mean average precision of the validation cohort of 0.68. The overall classification accuracy of six pulmonary critical imaging findings indicative of TB of the independent datasets was 81.08-91.05%. A moderate to strong correlation was demonstrated between the AI model-quantified TB score and the radiologist-estimated CT score. CONCLUSIONS: The proposed end-to-end AI system based on chest CT can achieve human-level diagnostic performance for early detection and optimal clinical management of patients with pulmonary TB. KEY POINTS: • Deep learning allows automatic detection, diagnosis, and evaluation of pulmonary tuberculosis. • Artificial intelligence helps clinicians to assess patients with tuberculosis. • Pulmonary tuberculosis disease activity and treatment management can be improved.

6.
J Tradit Chin Med ; 41(5): 739-746, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34708632

RESUMO

OBJEVTIVE: To investigate the effects of Cyclocarya paliurus (C. paliurus) polysaccharides on the spleen injury of diabetic rats. METHODS: Animals were divided into 6 groups, including normal group, model group, control group, low-dose group of C. paliurus polysaccharides treatment, middle-dose group of C. paliurus polysaccharides treatment and high-dose group of C. paliurus polysaccharides treatment. Histological analysis of spleen was analyzed using hematoxilin and eosin. Levels of biological parameters and anti-oxidative enzymes were determined by spectrophotometry. Interleukin-7 (IL-7) and IL-10 were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with that of model group, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase level increased 78.63% (P < 0.05), 51.76% (P < 0.05), 2.95 times (P < 0.01) and 41.11% (P < 0.05) in the high-dose group of C. paliurus polysaccharides treatment, respectively. IL-7 and IL-10 increase 1.66 (P < 0.01) and 1.21 times (P < 0.01) in the high-dose group of C. paliurus polysaccharides treatment, respectively. CONCLUSION: It is suggested that C. paliurus polysaccharides may play a protecting role for spleen injury of diabetic rats by enhancing the antioxidative ability and evaluating the immunity.

7.
Curr Gene Ther ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34636308

RESUMO

Bone marrow mesenchymal stem cells (BMSCs), multidirectional cells with self-renewal capacity, can differentiate into many cell types and play essential roles in tissue healing and regenerative medicine. Cell experiments and in vivo research in animal models have shown that BMSCs can repair degenerative discs by promoting cell proliferation and expressing extracellular matrix (ECM) components, such as type II collagen and protein-polysaccharides. Delaying or reversing the intervertebral disc (IVD) degeneration (IDD) process at an etiological level may be an effective strategy. However, despite increasingly in-depth research, some deficiencies in cell transplantation timing and strategy remain, preventing the clinical application of cell transplantation. Exosomes exhibit the characteristics of the mother cells from which they were secreted and can inhibit nucleus pulposus (NP) cell (NPC) apoptosis and delay IDD through intercellular communication. Furthermore, the use of exosomes effectively avoids problems associated with cell transplantation, such as immune rejection. This manuscript introduces almost all of the BMSCs and exosomes derived from BMSCs (BMSCs-Exos) described in the IDD literature. Many challenges regarding the use of cell transplantation and therapeutic exosome intervention for IDD remain to be overcome.

8.
J Integr Med ; 19(6): 555-560, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34696996

RESUMO

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare adverse cutaneous reaction with a low incidence and high mortality. Despite posing a serious threat to patients' health and lives, there is no high-quality evidence for a standard treatment regimen. Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN. After consensus-based regular treatments at a local hospital, his symptoms became worse. Thus, he consented to receive Chinese herbal medicine (CHM) therapy. The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day. After 7 days of treatment, the dead skin began peeling away from the former lesions that had covered his hands, feet, and lips, indicating that skin had regenerated. After 12 days of treatment, the patient's skin was completely recovered. In this case, SJS/TEN was successfully treated with Pi-Yan-Ning, suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments. Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.


Assuntos
Medicamentos de Ervas Chinesas , Síndrome de Stevens-Johnson , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Fatores Imunológicos , Incidência , Masculino , Pessoa de Meia-Idade , Pele , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia
9.
Pharm Biol ; 59(1): 1294-1304, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34543169

RESUMO

CONTEXT: Yang-Yin-Jie-Du Decoction (YYJDD) was used to improve gefitinib efficacy in our clinical practice, but its mechanism remains unclear. OBJECTIVE: This study explored if YYJDD could reverse gefitinib resistance. MATERIALS AND METHODS: H1975 cells were exposed to control, 10 µM gefitinib, 3.2 mg/mL YYJDD or combination treatment. Cell viability was detected by MTT during 0-96 h. Apoptosis and the PI3K/Akt proteins were tested by flow cytometry and western-blot at 24 h. LY294002 was applied to further determine the role of the PI3K/Akt. 23 BALB/c nude xenograft mice received normal saline (n = 5), 80 mg/kg gefitinib (n = 6), 2.35 g/kg lyophilised powder of YYJDD (n = 6) or combination treatment (n = 6) by gavage for 4 weeks and submitted to TUNEL, immunohistochemistry, and western-blot. RESULTS: In vitro, gefitinib (IC50: 20.68 ± 2.06 µM) and YYJDD (IC50: 6.6 ± 0.21 mg/mL) acted in a moderate synergistic way. Combination treatment inhibited cell viability from 100% to 25.66%. Compared to gefitinb (33.23 ± 3.99%), cell apoptosis was increased with combination treatment (54.11 ± 7.32%), accompanied by down-regulation of the PI3K/Akt. LY294002 further inhibited cell viability, increased apoptosis, and down-regulated p-Akt/Akt. In vivo, the tumour sizes in the combination group (1165.13 ± 157.79 mm3) were smaller than gefitinib alone (1630.66 ± 208.30 mm3). The positive rate of TUNEL staining was increased by combination treatment (22.33 ± 2.75%) versus gefitinib (7.37 ± 0.87%), while the PI3K/Akt was down-regulated. DISCUSSION AND CONCLUSION: YYJDD has potential to overcome gefitinib resistance. Future investigations should be focussed on its specific targets.

10.
Cancer Cell ; 39(10): 1388-1403.e10, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34506739

RESUMO

Localized radiotherapy (RT) induces an immunogenic antitumor response that is in part counterbalanced by activation of immune evasive and tissue remodeling processes, e.g., via upregulation of programmed cell death-ligand 1 (PD-L1) and transforming growth factor ß (TGF-ß). We report that a bifunctional fusion protein that simultaneously inhibits TGF-ß and PD-L1, bintrafusp alfa (BA), effectively synergizes with radiotherapy, leading to superior survival in multiple therapy-resistant murine tumor models with poor immune infiltration. The BA + RT (BART) combination increases tumor-infiltrating leukocytes, reprograms the tumor microenvironment, and attenuates RT-induced fibrosis, leading to reconstitution of tumor immunity and regression of spontaneous lung metastases. Consistently, the beneficial effects of BART are in part reversed by depletion of cytotoxic CD8+ T cells. Intriguingly, targeting of the TGF-ß trap to PD-L1+ endothelium and the M2/lipofibroblast-like cell compartment by BA attenuated late-stage RT-induced lung fibrosis. Together, the results suggest that the BART combination has the potential to eradicate therapy-resistant tumors while sparing normal tissue, further supporting its clinical translation.

11.
JNCI Cancer Spectr ; 5(4): pkab048, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34409252

RESUMO

Background: Immunotherapy yields survival benefit for some advanced stage non-small cell lung cancer (NSCLC) patients. Because highly predictive biomarkers of immunotherapy response are an unmet clinical need, we used pretreatment radiomics and clinical data to train and validate a parsimonious model associated with survival outcomes among NSCLC patients treated with immunotherapy. Methods: Three cohorts of NSCLC patients treated with immunotherapy were analyzed: training (n = 180), validation 1 (n = 90), and validation 2 (n = 62). The most informative clinical and radiomic features were subjected to decision tree analysis, which stratified patients into risk groups of low, moderate, high, and very high risk of death after initiation of immunotherapy. All statistical tests were 2-sided. Results: The very high-risk group was associated with extremely poor overall survival (OS) in validation cohorts 1 (hazard ratio [HR] = 5.35, 95% confidence interval [CI] = 2.14 to 13.36; 1-year OS = 11.1%, 95% CI = 1.9% to 29.8%; 3-year OS = 0%) and 2 (HR = 13.81, 95% CI = 2.58 to 73.93; 1-year OS = 47.6%, 95% CI = 18.2% to 72.4%; 3-year OS = 0%) when compared with the low-risk group (HR = 1.00) in validation cohorts 1 (1-year OS = 85.0%, 95% CI = 60.4% to 94.9%; 3-year OS = 38.9%, 95% CI = 17.1% to 60.3%) and 2 (1-year OS = 80.2%, 95% CI = 40.3% to 94.8%; 3-year OS = 40.1%, 95% CI = 1.3% to 83.5%). The most informative radiomic feature, gray-level co-occurrence matrix (GLCM) inverse difference, was positively associated with hypoxia-related carbonic anhydrase 9 using gene-expression profiling and immunohistochemistry. Conclusion: Utilizing standard-of-care imaging and clinical data, we identified and validated a novel parsimonious model associated with survival outcomes among NSCLC patients treated with immunotherapy. Based on this model, clinicians can identify patients who are unlikely to respond to immunotherapy.

12.
Anal Bioanal Chem ; 413(25): 6253-6266, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34415362

RESUMO

Allergic diseases are a significant public health problem worldwide. Traditional Chinese medicines (TCMs) with reported anti-allergy effects may be important sources for the development of new anti-allergy drugs. Thus, establishing an analytical method that can simultaneously identify and screen anti-allergic compounds in TCMs is important. The increased concentrations of intracellular calcium ions resulting in mast cell degranulation releasing active mediators play a key role in allergic diseases, which can be used as a potential index to identify anti-allergic herbs and compounds. In this study, we provide a new strategy that was applied to screening natural anti-allergic compounds based on fluorescence calcium ion (Ca2+) fluctuation integrated with cell extract and high-performance liquid chromatography-mass spectrometry (HPLC-MS). A low-cost, convenient fluorescence detection Ca2+ signaling method was established and successfully applied to identify three herbs. Then, the method was integrated with biospecific cell fishing and HPLC-MS to screen potential active components that have the effect of stabilizing the cell membrane of rat basophilic leukemia granulocytes (RBL-2H3). Seven components, namely, albiflorin and paeoniflorin from Radix Paeoniae Alba, ononin and formononetin from Radix Astragali, cimifugin, 4'-O-ß-D-glucosyl-5-O-methylvisamminol, and prim-O-glucosylcimifugin from Radix Saposhnikoviae were fished. These seven compounds have the effect of inhibiting cell Ca2+ influx. 4'-O-ß-D-Glucosyl-5-O-methylvisamminol, prim-O-glucosylcimifugin, paeoniflorin, ononin, and formononetin significantly inhibit the release of ß-hexosaminidase, which is equivalent to the positive drug. In conclusion, the integrated strategy of fluorescence detection calcium ion kinetic method binding with biospecific cell fishing was an effective mode to identify and screen natural anti-allergic compounds.

13.
Biomed Res Int ; 2021: 4356949, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395614

RESUMO

Irreversible loss of retinal ganglion cells (RGCs) is a common pathological feature of various optic nerve degenerative diseases such as glaucoma and ischemic optic neuropathy. Effective protection of RGCs is the key to successful treatment of these diseases. Total Panax notoginseng saponins (TPNS) are the main active component of Panax notoginseng, which has an inhibitory effect on the apoptosis pathway. This study is aimed at assessing the protective effect of TPNS on RGCs of the optic nerve crush (ONC) model of rats and exploring the underlying mechanisms. The intraperitoneal or intravitreal injection of TPNS was used based on the establishment of the rat ONC model. Fifteen days after the injury, the cell membrane fluorescent probe (Fluoro-Gold) was applied to retrograde RGCs through the superior colliculus and obtain the number of surviving RGCs. TUNEL assay was also used to detect the number and density of RGC apoptosis after the ONC model. The expression and distribution of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK in the retina were demonstrated by Western blot analysis. After the intervention of TPNS, the rate of cell survival increased in different retinal regions (p < 0.05) and the number of apoptosis cells decreased. Regarding the expression of Bcl-2/Bax, c-Jun/P-c-Jun, and P-JNK-related apoptotic proteins, TPNS can reduce the level of apoptosis and play a role in protecting RGCs (p < 0.05). These findings indicate that topical administration of TPNS can inhibit cell apoptosis and promote RGC survival in the crushed optic nerve.


Assuntos
Lesões por Esmagamento/tratamento farmacológico , Traumatismos do Nervo Óptico/tratamento farmacológico , Panax notoginseng/química , Células Ganglionares da Retina/efeitos dos fármacos , Saponinas/administração & dosagem , Animais , Apoptose , Biomarcadores/metabolismo , Sobrevivência Celular , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Injeções Intraperitoneais , Injeções Intravítreas , Masculino , Traumatismos do Nervo Óptico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Ratos , Células Ganglionares da Retina/metabolismo , Saponinas/farmacologia , Resultado do Tratamento
14.
Glob Health Action ; 14(1): 1959708, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34420496

RESUMO

BACKGROUND: Cardiovascular diseases (CVDs) are the leading causes of death in China. Little is known about the CVD burden and risk factors in Henan Province, China. OBJECTIVE: To analyze the CVD burden and main risk factors between 1990 and 2017 in the Henan Province in China. METHODS: The methodological framework and analytical strategies adopted in the Global Burden of Disease Study 2017 were used. RESULTS: (1) Age-standardized mortality rate attributed to CVDs increased from 355.0 per 100,000 persons in 1990 to 364.1 per 100,000 persons in 2017 in Henan. (2) Age-standardized disability adjusted life years (DALYs) rate fell by 3.9% from 1990 to 2017. However, the number of DALYs attributed to CVDs increased by 75.9% from 4.2 million person-years in 1990 to 7.3 million person-years in 2017. (3) The age-standardized years lived with disability (YLDs) rate increased by 27.5% from 1990 to 2017. However, years of life lost (YLLs) rate decreased by 6.7% from 1990 to 2017. The contribution of YLLs to the DALYs decreased from 91.4% in 1990 to 89.2% in 2017. (4) Stroke (52.3%) and ischemic heart diseases (38.8%) accounted for 91.1% of total CVDs DALYs among adults in 2017. (5) Dietary factors such as high intake of sodium, alcohol use and low intake of fruits, high systolic blood pressure, and tobacco use were the top risk factors for CVDs, and the estimated population attributable fraction in 2017 was 69.4%, 56.7% and 25.2%, respectively. CONCLUSIONS: The absolute burden of CVDs in Henan is still high, although age-standardized DALYs declined between 1990 and 2017. The prevention and control of stroke and ischemic heart diseases should focus on a few modifiable risk factors which mainly contributed to the burden of CVDs, such as dietary factors, high systolic blood pressure, and tobacco use.


Assuntos
Doenças Cardiovasculares , Pessoas com Deficiência , Adulto , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Efeitos Psicossociais da Doença , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco
15.
J Alzheimers Dis ; 83(2): 799-818, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366339

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a degenerative disorder, accompanied by progressive cognitive decline, for which there is no cure. Recently, the close correlation between AD and type 2 diabetes mellitus (T2DM) has been noted, and a promising anti-AD strategy is the use of anti-T2DM drugs. OBJECTIVE: To investigate if the novel glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist DA4-JC shows protective effects in the triple APP/PS1/tau mouse model of AD. METHODS: A battery of behavioral tests were followed by in vivo recording of long-term potentiation (LTP) in the hippocampus, quantified synapses using the Golgi method, and biochemical analysis of biomarkers. RESULTS: DA4-JC improved cognitive impairment in a range of tests and relieved pathological features of APP/PS1/tau mice, enhanced LTP in the hippocampus, increased numbers of synapses and dendritic spines, upregulating levels of post-synaptic density protein 95 (PSD95) and synaptophysin (SYP), normalized volume and numbers of mitochondria and improving the phosphatase and tensin homologue induced putative kinase 1 (PINK1) - Parkin mitophagy signaling pathway, while downregulating amyloid, p-tau, and autophagy marker P62 levels. CONCLUSION: DA4-JC is a promising drug for the treatment of AD.

16.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2699-2709, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296566

RESUMO

The cross combination of dry-method(network pharmacology analysis) and wet-method(high-resolution mass spectro-metry with antioxidation experiment) was used to predict antioxidant quality markers(Q-markers) of Hippophae tibetana. Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) was developed to rapidly separate and identify the chemical constituents in H. tibetana. Then in DPPH free radicals and superoxide anion scavenging experiment, the antioxidant activity of the four different polar parts with extracts of petroleumether, ethyl acetate, n-butanol and water was evaluated. Network pharmacology method was used for functional enrichment and pathway analysis to screen antioxidant-related components and preliminarily explain the mechanism of action. On this basis, multi-source information was integrated to predict the antioxidant Q-markers. The results showed that 51 components in H. tibetana were identified, including 18 flavonoids, 14 terpenoids, 6 alkaloids, 4 coumarins and phenylpropanoids, 3 volatile components and 2 polyphenols. The antioxidant capacity of different fractions: ethyl acetate > n-butanol > water > petroleum ether. The medicine mainly acted on PI3 K-Akt and FoxO signaling pathways to perform antioxidant effects through flavonoids such as quercetin, luteolin and kaempferol. According to the results of dry-method and wet-method, quercetin, luteolin and kaempferol, the representatives of poly-hydroxy flavone, may be the antioxidant Q-markers of H. tibetana. In this study, with the antioxidant Q-markers of H. tibetana as an example, an investigation model of predicting Q-marker was discussed based on the ternary system of composition, function and informatics, providing a scientific basis for the establishment of quality evaluation standards for H. tibetana.


Assuntos
Antioxidantes , Hippophae , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Tecnologia
17.
Exp Ther Med ; 22(3): 933, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34306202

RESUMO

Aberrations in long noncoding RNA (lncRNA) expression have been recognized in numerous human diseases. In the present study, the of role the long noncoding RNA HOX antisense intergenic RNA myeloid 1 variant (HOTAIRM1-1) in regulating the pathological progression of osteoarthritis (OA) was investigated. The aberrant expression of HOTAIRM1-1 in OA was demonstrated, but the molecular mechanisms require further analysis. The aim of the present study was to explore the function of miR-125b in modulating chondrocyte viability and apoptosis, and to address the functional association between HOTAIRM1-1 and miR-125b as potential targets. A miR-125b inhibitor was used, which laid the foundation for the following investigation. The study confirmed that HOTAIRM1-1 and miR-125b are inversely expressed in chondrocytes. The expression of HOTAIRM1-1 was downregulated and the expression of miR-125b was upregulated in tissues from patients with OA. HOTAIRM1-1 directly interacted with miR-125b in chondrocytes. HOTAIRM1-1 knockdown was associated with chondrocyte proliferation and extracellular matrix degradation. Furthermore, miR-125b reversed the effect of HOTAIRM1-1 on cell proliferation and apoptosis. In conclusion, the present study indicates that the loss of HOTAIRM1-1 function leads to aberrant increases in the proliferation and apoptosis of chondrocytes. miR-125b may be a potential downstream mechanism that regulates the function of HOTAIRM1-1, and this finding provides a therapeutic strategy for OA.

18.
Sheng Li Xue Bao ; 73(3): 471-481, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34230948

RESUMO

Sleep exerts important functions in the regulation of cognition and emotion. Recent studies have found that sleep disorder is one of the important risk factors for Alzheimer's disease (AD), but the effects of chronic sleep deprivation on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1/tau triple transgenic AD model (3xTg-AD) mice and wild type (WT) mice (n = 8 for each group) were subjected to chronic sleep deprivation by using the modified multiple platform method, with 20 h of sleep deprivation each day for 21 days. Then, open field test, elevated plus maze test, sugar water preference test, object recognition test, Y maze test and conditioned fear memory test were performed to evaluate anxiety- and depression-like behaviors, and multiple cognitive functions. In addition, the immunohistochemistry technique was used to observe pathological characteristics in the hippocampus of mice. The results showed that: (1) Chronic sleep deprivation did not affect anxiety- (P = 0.539) and depression-like behaviors (P = 0.874) in 3xTg-AD mice; (2) Chronic sleep deprivation exacerbated the impairments of object recognition memory (P < 0.001), working memory (P = 0.002) and the conditioned fear memory (P = 0.039) in 3xTg-AD mice; (3) Chronic sleep deprivation increased amyloid ß (Aß) deposition (P < 0.001) and microglial activation (P < 0.001) in the hippocampus of 3xTg-AD mice, without inducing abnormal tau phosphorylation and neurofibrillary tangles. These results indicate that chronic sleep deprivation exacerbates the impairments of recognition memory, working memory and conditioned fear memory in 3xTg-AD mice by aggravating Aß deposition and the excessive activation of microglia in the hippocampus.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide/genética , Animais , Cognição , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1 , Privação do Sono , Proteínas tau
19.
Chin Med J (Engl) ; 134(16): 1933-1940, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34267069

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the fourth cause of cancer death in China. We aimed to provide national and subnational estimates and changes of CRC premature mortality burden during 2005-2020. METHODS: Data from multi-source on the basis of the national surveillance mortality system were used to estimate mortality and years of life lost (YLL) of CRC in the Chinese population during 2005-2020. Estimates were generated and compared for 31 provincial-level administrative divisions in China. RESULTS: Estimated CRC deaths increased from 111.41 thousand in 2005 to 178.02 thousand in 2020; age-standardized mortality rate decreased from 10.01 per 100,000 in 2005 to 9.68 per 100,000 in 2020. Substantial reduction in CRC premature mortality burden, as measured by age-standardized YLL rate, was observed with a reduction of 10.20% nationwide. Marked differences were observed in the geographical patterns of provincial units, and they appeared to be obvious in areas with higher economic development. Population aging was the dominant driver which contributed to the increase in CRC deaths, followed by population growth and age-specific mortality change. CONCLUSIONS: Substantial discrepancies were observed in the premature mortality burden of CRC across China. Targeted considerations were needed to promote a healthy lifestyle, expand cost-effective CRC early screening and diagnosis, and improve medical treatment to reduce CRC mortality among high-risk populations and regions with inadequate healthcare resources.


Assuntos
Neoplasias Colorretais , China/epidemiologia , Humanos
20.
Cancer Cell Int ; 21(1): 323, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183010

RESUMO

BACKGROUND: The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear. METHODS: MAZ expression was examined in ccRCC and normal kidney tissue by quantitative real-time PCR and Western blot. Statistical analysis was used to evaluate the clinical correlation between MAZ expression and clinicopathological characteristics to determine the relationship between MAZ expression and the survival of ccRCC patients. The biological roles of MAZ in cells were investigated in vitro using MTT and colony assays. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to investigate the relationship between MAZ and its potential downstream signaling molecules. RESULTS: MAZ expression is elevated in ccRCC tissues, and higher levels of MAZ were correlated with poor survival of patients with ccRCC. MAZ upregulation elevates the proliferation ability of ccRCC cells in vitro, whereas silencing MAZ represses this ability. Our results further reveal that MAZ promotes cell growth, which is dependent on ERK signaling. Importantly, we found that MAZ positively regulates MAP2K2 expression in ccRCC cells. Mechanistically, MAZ binds to the MAP2K2 promoter and increases MAP2K2 transcription. Furthermore, MAP2K2 levels were shown to be increased in ccRCC tissues and to be associated with a poor prognosis of ccRCC patients. MAP2K2 upregulation activates the ERK signaling pathway and promotes ccRCC progression. CONCLUSION: These results reveal that the MAZ/MAP2K2/ERK signaling axis plays a crucial role in promoting ccRCC progression, which suggests the potential therapeutic utility of MAZ in ccRCC.

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