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1.
J Alzheimers Dis ; 100(1): 229-237, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38788075

RESUMO

Background: Multiple studies have demonstrated that the gut microbiome is closely related to the onset of Alzheimer's disease, but the causal relationship between the gut microbiome and AD, as well as potential mediating factors, have not been fully explored. Objective: Our aim is to validate the causal relationship between the gut microbiome and the onset of AD and determine the key mechanism by which the gut microbiome mediates AD through blood metabolites using Mendelian randomization (MR) analysis methods. Methods: We first conducted bidirectional and mediating MR analyses using gut microbiota, blood amino acid metabolites, and AD-related single nucleotide polymorphisms as research data. In the analysis process, the inverse variance-weighted average method was mainly used as the primary method, with other methods serving as supplementary evidence. Results: Ultimately, we found that six types of gut bacteria and two blood amino acid metabolites have a causal effect on AD. Subsequent mediation analysis proved that decreased glutamine concentration mediates the negative causal effect of Holdemanella bacteria on AD (mediation ratio of 14.5%), and increased serum alanine concentration mediates the positive causal effect of Parabacteroide bacteria on AD (mediation ratio of 9.4%). Conclusions: Our study demonstrates the causality of Holdemanella and Parabacteroides bacteria in the onset of AD and suggests that the reduced glutamine and increased alanine serums concentration may be key nodes in mediating this effect.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Doença de Alzheimer/microbiologia , Doença de Alzheimer/genética , Doença de Alzheimer/sangue , Aminoácidos/sangue , Aminoácidos/metabolismo
2.
Mol Ecol Resour ; 2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37688468

RESUMO

Ecological restoration of mangrove ecosystems that became susceptible to recent habitat perturbations is crucial for tropical coast conservation. The white mangrove Laguncularia racemosa, a pioneer species inhabiting intertidal environments of the Atlantic East Pacific (AEP) region, has been used for reforestation in China for decades. However, the molecular mechanisms underlying its fast growth and high adaptive potential remain unknown. Using PacBio single-molecule real-time sequencing, we completed a high-quality L. racemosa genome assembly covering 1105 Mb with scaffold N50 of 3.46 Mb. Genomic phylogeny shows that L. racemosa invaded intertidal zones during a period of global warming. Multi-level genomic convergence analyses between L. racemosa and three native dominant mangrove clades show that they experienced convergent changes in genes involved in nutrient absorption and high salinity tolerance. This may explain successful L. racemosa adaptation to stressful intertidal environments after introduction. Without recent whole-genome duplications or activated transposable elements, L. racemosa has retained many tandem gene duplications. Some of them are involved in auxin biosynthesis, intense light stress and cold stress response pathways, associated with L. racemosa's ability to grow fast under high light or cold conditions when used for reforestation. In summary, our study identifies shared mechanisms of intertidal environmental adaptation and unique genetic changes underlying fast growth in mangrove-unfavourable conditions and sheds light on the molecular mechanisms of the white mangrove utility in ecological restoration.

3.
Front Immunol ; 14: 1193835, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37662911

RESUMO

Background: Tendinopathy is a growing global concern affecting many people, like athletes, workers, and the elderly. Despite its commonality among the sporting population, there is no practical clinical guideline for patellar tendinopathy (PT). Furthermore, there is conflicting evidence between clinical guidelines on shockwave therapy's application and clinical utility for Achilles tendinopathy (AT) and plantar fasciitis (PF). Thus, our aim of this study is to evaluate the evidence for shockwave therapy; to provide a Grading of Recommendation, Assessment, Development and Evaluation (GRADE) level of the evidence and effectiveness of shockwave therapy for patellar tendinopathy, Achilles tendinopathy, and Plantar fasciitis. Method: Medical Literature Analysis and Retrieval System Online (Medline), Embase, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro) and China National Knowledge Infrastructure database (CNKI) were searched to find relevant studies published before December 14th, 2022. Results: Our study showed that for PT in the short term, extracorporeal shockwave therapy (ESWT) or ESWT + eccentric exercise (EE) has a negligible effect on pain and function compared to a placebo or placebo + EE. On the contrary, ESWT significantly affects pain compared to conservative treatment (CT). For AT, ESWT has a small inconclusive effect on pain and function in the short term compared to EE. On the other hand, a placebo outperformed ESWT in improving function for AT but not pain outcomes. PF showed that ESWT significantly affects short- and long-term pain and function. When ESWT was compared to other interventions such as low laser therapy (LLLT), corticosteroid injection (CSI), or CT, there was a small inconclusive effect on pain and function in the short term. Conclusion: There is low-moderate evidence that ESWT has a negligible effect on pain and function for PT and AT. However, high-quality evidence suggests ESWT has a large effect on pain and function for PF. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396835, identifier CRD42023396835.


Assuntos
Tendão do Calcâneo , Tratamento por Ondas de Choque Extracorpóreas , Fasciíte Plantar , Ondas de Choque de Alta Energia , Doenças Musculoesqueléticas , Tendinopatia , Idoso , Humanos , Fasciíte Plantar/terapia , Ondas de Choque de Alta Energia/uso terapêutico , Tendinopatia/terapia
4.
Chem Commun (Camb) ; 59(60): 9271-9274, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37431649

RESUMO

Ice nucleation plays a vital function in various fields. In this study, we prepared hydrogel surfaces with different cross-linkages by pH-modulating the coordination pattern of Fe3+ and catechol. We found that the ice nucleation temperature decreases with increasing cross-linkages. Further analysis shows that the hydrogel surfaces with different cross-linking degrees could achieve the regulation of ice nucleation by modulating the interfacial water. Our study elucidates the mechanism of ice nucleation regulated by interfacial water in soft matter and proposes a new method for preparing ice nucleation-regulated material.

5.
Sci Rep ; 13(1): 10728, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400510

RESUMO

Strength training is recommended by the American Physical Therapy Association to improve muscle strength, mobility, and balance following knee replacement. Few studies have focused on the direct effects of strength training on functional ambulation, and potential dose-response relationships between strength training parameters and the effect remain unclear. The aim of this systematic review, meta-analysis, and meta-regression was to evaluate the effects of strength training on functional ambulation following knee replacement (KR). We also aimed to explore potential dose-response relationships between strength training parameters and performance in functional ambulation. A systematic literature search of eight online databases was performed on March 12, 2023, for randomized controlled trials evaluating the effects of strength training on functional ambulation by six-minute walk test (6MWT) or timed-up and go test (TUG) after KR. Data were pooled by random-effect meta-analyses and presented as weighted mean difference (WMD). A random-effect meta-regression was performed for four predetermined training parameters, namely, duration (weeks), frequency (sessions per week), volume (time per session), and initial time (after surgery) separately to explore dose-response relationships with WMD. Fourteen trials encompassing 956 participants were included in our study. Meta-analyses showed an improvement in 6MWT performance after strength training (WMD: 32.15, 95% CI 19.44-44.85) and a decrease in time to complete TUG (WMD: - 1.92, 95% CI - 3.43 to - 0.41). Meta-regression revealed a dose-response relationship only between volume and 6MWT, with a decreasing trend (P = 0.019, 95% CI - 1.63 to - 0.20). Increasing trends of improvement in 6MWT and TUG were observed with increasing training duration and frequency. A slight decreasing trend of improvement was observed in 6MWT with postponed initial time, while an opposite trend was observed in TUG. Based on existing studies, moderate-certainty evidence suggests that strength training could increase 6MWT distance, and low-certainty evidence shows that strength training could decrease the time to complete TUG after KR. Meta-regression results only suggested a dose-response relationship between volume and 6MWT with a decreasing trend.Registration: PROSPERO: CRD42022329006.


Assuntos
Treinamento Resistido , Humanos , Treinamento Resistido/métodos , Caminhada , Força Muscular/fisiologia
6.
Integr Med Res ; 12(2): 100945, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37122485

RESUMO

Background: To meet the growing global demand for rehabilitation services, the World Health Organization (WHO) launched Rehabilitation 2030. This study was commissioned by the WHO to investigate the integration degree of traditional Chinese medicine (TCM) in Chinese health system rehabilitation services and the demand for TCM rehabilitation in China. Methods: Twenty TCM rehabilitation experts and relevant government administrators were invited to complete the questionnaire between September 2019 and January 2022. The development of traditional, complementary, and integrative medicine (TCI) rehabilitation in China was assessed primarily based on six different health system components. Results: 26 policies, regulations, and national strategic plans related to TCI rehabilitation were issued by relevant government departments since 2002; notably, 14 policies related to TCI rehabilitation development were intensively introduced from 2016 to 2021. These policies cover the three main areas of financing, infrastructure development, and service delivery. The National Administration of Traditional Chinese Medicine's investment in TCM clinical capacity infrastructure and scientific research in 2019-2021 increased by 66% compared to 2010-2012, and the average number of TCM hospitals with rehabilitation departments in 2020 increased by 6.5% compared to 2018. The proportion of community health service centers providing TCM services in primary medical and health institutions has increased by 30.8% over the past 10 years. Conclusion: Long-term continuous policies, substantial financial investment, and expansion of the scope of TCI rehabilitation services in primary care institutions have effectively contributed to the rapid development of TCI rehabilitation. However, human resources and financing mechanisms for TCI rehabilitation need further improvement.

7.
Int J Mol Med ; 51(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36660951

RESUMO

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the ß­actin control western blotting data featured in Fig. 3E were strikingly similar to data appearing in different form in another article by different authors. Upon asking the authors to explain this phenomenon, they were unable to provide the raw data for this experiment. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 847­856, 2019; DOI: 10.3892/ijmm.2019.4257].

8.
Transl Oncol ; 27: 101564, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36252282

RESUMO

CD3+CD4-CD8- double-negative T (DNT) cells are new weapons in cancer immunotherapy. Here, we explored DNT cells in malignant pleural effusions (MPEs) from lung cancer patients. DNT cells, especially TCRαß+CD56- DNT cells, were increased in MPE from lung cancer patients. DNT cells highly expressed PD-1, TRAIL, NKG2D and DNAM-1. In contrast, FasL was barely detected in DNT cells. Compared with non-MPE cells, MPE-derived DNT cells expressed much higher levels of PD-1 and TRAIL. DNT cells from healthy peripheral blood donors potentially killed lung cancers, which was decreased by MPE supernatant. Exosomes from MPE supernatant expressed PD-1 and CEACAM1 and impaired the cytotoxicity of DNT cells. Blocking PD-1 and TIM3 rescued the cytotoxicity of DNT cells treated with MPE-derived exosomes. Overall, we demonstrated that the frequency of DNT cells in MPE from lung cancer patients was increased and that MPE-derived exosomes impaired the cytotoxicity of DNT cells via the PD-1/PD-L1 and CEACAM1/TIM3 pathways.

9.
J Mol Model ; 28(11): 364, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36271993

RESUMO

Bending modulus is a key parameter to characterize the stiffness of materials. Commonly, it is believed that the bending modulus is closely related to the thickness as described by the thin plate theory. However, the thin plate theory fails in multilayer van der Waals materials like multilayer graphene, suggesting a more complex relationship between the bending modulus and thickness. Here, rippled graphene structures containing non-hexagonal carbon rings with different thicknesses are constructed to study the thickness-dependent bending modulus by the first-principles calculations. It is found that the bending modulus of rippled graphene depends on several factors, such as geometry, bending curvature, and thickness. Particularly, for the egg-tray graphene structures with similar structural pattern and bending curvature, i.e., eliminating the effects of structural pattern and bending curvature, the bending modulus could show a linear relationship to the thickness. Moreover, this linear relationship is very robust even in the case of changing the thickness through heteroatom doping.

10.
Front Med (Lausanne) ; 9: 936314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052330

RESUMO

Background: Sarcopenia is the age-related loss of skeletal muscle mass and function; it is a risk factor for falls among older individuals. Few studies have focused on training such individuals to adopt a safe-landing strategy that would protect them from fall-related injuries. Ditangquan is a traditional Chinese martial art comprising movements that conform to the principles of safe landing. This study aims to investigate the effectiveness of Ditangquan in preventing fall-related injuries among older individuals with sarcopenia. Methods: A total of 70 participants (21 males and 49 females with sarcopenia) between 60 and 80 years of age were recruited from three local communities and randomly assigned to the Ditangquan exercise group (DG) or the control group (CG) in a 1:1 ratio. Three times a week for 24 weeks, both the DG and CG received an hour of conventional exercise and an hour of Ditangquan exercise based on safe landing. Primary outcomes were the modified falls efficacy scale (MFES), the number of falls, and fall injuries; the secondary outcome was the Timed Up & Go (TUG) test. Results: The DG had significantly fewer falls (1 vs. 8, P = 0.028) and fall injuries (0 vs. 6, P = 0.025) than the CG. Furthermore, at the end of the study, the DG had a significantly improved MFES (mean difference: 32.17 scores; 95% CI: 21.32, 43.02; P <0.001) and TUGT (mean difference: -4.94 s; 95% CI: -7.95, -1.93; P = 0.002) as compared with the CG. Conclusion: Ditangquan exercise based on the safe-landing strategy effectively improves the functional mobility of the elderly, reduces the occurrence of falls and injuries, and increases the individual's confidence in preventing falls.

11.
Front Aging Neurosci ; 14: 872233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35645784

RESUMO

Sarcopenia has become a key challenge for healthy aging in older adults. However, it remains unclear whether traditional Chinese medicine can effectively treat sarcopenia. This systematic review analyzes the current evidence for the effect of traditional Chinese medicine (TCM) on sarcopenia. We searched for articles regarding sarcopenia treated by TCM in Cochrane library, PubMed, SinoMed, Web of Science, Embase, and the China National Knowledge Infrastructure (from inception until 10 December 2021). Two researchers independently screened the literature in accordance with the inclusion and exclusion criteria designed by PICOS principles. The risk of bias was assessed by the Cochrane Risk of Bias (ROB) tool. The quality of evidence was assessed by the grading of recommendations, assessment, development, and evaluation (GRADE). Participants' characteristics, interventions, and the relevant results of the included studies were extracted and synthesized in a narrative way. The total number of participants in the 21 included studies was 1,330. Most of the studies evaluated physical function (n = 20) and muscle strength (n = 18), and a small number of studies (n = 6) assessed muscle mass. Overall, it was found that TCM had a positive impact on muscle strength (grip strength, chair stand test) and physical function (6-m walking speed, timed up and go test, sit and reach) in patients with sarcopenia, inconsistent evidence of effects on muscle mass. However, the small sample size of the included studies led to imprecision in the results, and the presence of blinding of the studies, allocation concealment, and unreasonable problems with the control group design made the results low grade. Among these results, the quality of evidence for grip strength (n = 10) was of medium grade, and the quality of evidence related to the remaining indicators was of low grade. This systematic review showed that traditional Chinese Qigong exercises and Chinese herbal medicine have a positive and important effect on physical performance and muscle strength in older adults with sarcopenia. Future high-quality multicenter randomized controlled trials (RCTs) with large samples are needed to determinate whether acupuncture and other therapies are effective in treating sarcopenia.

12.
Molecules ; 27(2)2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35056702

RESUMO

PI3Kα is one of the potential targets for novel anticancer drugs. In this study, a series of 2-difluoromethylbenzimidazole derivatives were studied based on the combination of molecular modeling techniques 3D-QSAR, molecular docking, and molecular dynamics. The results showed that the best comparative molecular field analysis (CoMFA) model had q2 = 0.797 and r2 = 0.996 and the best comparative molecular similarity indices analysis (CoMSIA) model had q2 = 0.567 and r2 = 0.960. It was indicated that these 3D-QSAR models have good verification and excellent prediction capabilities. The binding mode of the compound 29 and 4YKN was explored using molecular docking and a molecular dynamics simulation. Ultimately, five new PI3Kα inhibitors were designed and screened by these models. Then, two of them (86, 87) were selected to be synthesized and biologically evaluated, with a satisfying result (22.8 nM for 86 and 33.6 nM for 87).


Assuntos
Simulação de Acoplamento Molecular
13.
Cancer Gene Ther ; 29(6): 770-783, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34145425

RESUMO

Primary cytoreductive surgery with platinum-taxane-based chemotherapy is the standard treatment for ovarian cancer (OC) patients; however, resistance to chemotherapy is a contributing factor to OC mortality. Paclitaxel (PTX), the most widely used taxane, has become the first-line drug against OC. The molecular mechanism of PTX resistance is different from that of platinum-based agents and is still not completely elucidated. Our previous study showed that glucose-regulated protein 78 (GRP78) is involved in the resistance of OC cells to PTX. However, little is known regarding endogenous inhibitors of this gene. MicroRNAs (miRNAs) play critical roles in the regulation of gene expression; therefore, we sought to identify miRNA(s) with potential to target GRP78 under the hypothesis that miRNA(s) could serve as potential therapeutic targets. Here, we show that miR-181c, predicted to target GRP78, was downregulated in PTX-resistant OC cells and tissues. MiR-181c downregulated GRP78 expression and induced apoptosis by directly targeting its 3'-untranslated region (UTR). Overexpression of miR-181c sensitized resistant OC to PTX by inhibiting the PI3K/Akt pathway in vitro and in vivo. Taken together, our findings indicate that the delivery of miR-181c can efficiently suppress GRP78 expression and GRP78-mediated PTX resistance in OC and suggest that this strategy has therapeutic potential.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Regiões 3' não Traduzidas , Carcinoma Epitelial do Ovário/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Chaperona BiP do Retículo Endoplasmático/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
14.
Clin Transl Immunology ; 10(6): e1300, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178329

RESUMO

OBJECTIVE: The IL-33/ST2 axis has been extensively investigated in type 2 eosinophilic inflammation. Here, we aimed to investigate the role of the IL-33/ST2 axis in neutrophil-dominant allergic airway inflammation. METHODS: House-dust mite (HDM) extract and lipopolysaccharide (LPS) were administered to establish a murine model of neutrophil-dominant allergic airway inflammation. The formation of neutrophilic extracellular traps (NETs) in the lung tissues was demonstrated by immunofluorescence imaging. Mature IL-33 in bronchoalveolar lavage fluid (BALF) was detected by Western blotting. The neutrophilic chemokine KC produced by bone marrow-derived macrophages (BMDMs) or primary alveolar epithelial cells was measured with a commercial ELISA kit. RESULTS: In the present study, we observed neutrophilic inflammation and tight junction damage in the lungs of mice sensitised with HDM and LPS. Furthermore, sensitisation with HDM and LPS resulted in the formation of NETs, accompanied by increased levels of mature IL-33 in the BALF. Moreover, LPS damaged the epithelial tight junction protein occludin directly or indirectly by inducing NET formation. Surprisingly, IL-33 deficiency augmented neutrophilia and epithelial barrier injury in the lungs of mice after sensitisation with HDM and LPS. Similarly, the absence of ST2 exacerbated the neutrophilic inflammatory response, decreased the expression of occludin and exacerbated the severity of neutrophil-dominant allergic airway inflammation in an HDM/LPS-induced mouse model. Mechanistically, BMDMs and alveolar epithelial cells from IL-33- or ST2-deficient mice tended to produce higher levels of the neutrophilic chemokine KC. CONCLUSIONS: These results demonstrated that the IL-33/ST2 axis may play a protective role in neutrophil-dominant allergic airway inflammation.

15.
Int J Genomics ; 2021: 8105124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33604369

RESUMO

HD-ZIP is a unique type of transcription factor in plants, which are closely linked to the regulation of plant growth and development, the response to abiotic stress, and disease resistance. However, there is little known about the HD-ZIP gene family of pepper. In this study, 40 HD-ZIP family members were analyzed in the pepper genome. The analysis indicated that the introns number of Ca-HD-ZIP varied from 1 to 17; the number of amino acids was between 119 and 841; the theoretical isoelectric point was between 4.54 and 9.85; the molecular weight was between 14.04 and 92.56; most of them were unstable proteins. The phylogenetic tree divided CaHD-ZIP into 4 subfamilies; 40 CaHD-ZIP genes were located on different chromosomes, and all of them contained the motif 1; two pairs of CaHD-ZIP parallel genes of six paralogism genes were fragment duplications which occurred in 58.28~88.24 million years ago. There were multiple pressure-related action elements upstream of the start codon of the HD-Z-IP family. Protein interaction network proved to be coexpression phenomenon between ATML1 (CaH-DZ22, CaHDZ32) and At4g048909 (CaHDZ12, CaHDZ31), and three regions of them were highly homology. The expression level of CaHD-ZIP gene was different with tissues and developmental stages, which suggested that CaHD-ZIP may be involved in biological functions during pepper progress. In addition, Pepper HD-ZIP I and II genes played a major role in salt stress. CaHDZ03, CaHDZ 10, CaHDZ17, CaHDZ25, CaHDZ34, and CaHDZ35 were significantly induced in response to salt stress. Notably, the expression of CaHDZ07, CaHDZ17, CaHDZ26, and CaHDZ30, homologs of Arabidopsis AtHB12 and AtHB7 genes, was significantly upregulated by salt stresses. CaHDZ03 possesses two closely linked ABA action elements, and its expression level increased significantly at 4 h under salt stress. qRT-P-CR and transcription analysis showed that the expression of CaHDZ03 and CaHDZ10 was upregulated under short-term salt stress, but CaHDZ10 was downregulated with long-term salt stress, which provided a theoretical basis for research the function of Ca-HDZIP in response to abiotic stress.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33293989

RESUMO

Vascular endothelial dysfunction is an essential and early sign of diabetic macroangiopathy, a primary complication of diabetes mellitus. Astragalus membranaceous-Angelica sinensis is a classic medical combination applied in China to treat diabetes mellitus. The aim of this study was to investigate the effect of the granule form of the extract produced from the dried root of Astragalus membranaceous (AM) combination with the granule form of the extract produced from the dried Angelica sinensis (AS) on diabetic macroangiopathy and its underlying mechanism. Herein, rats were treated by AM-AS at a ratio of 3 : 2 via intragastric administration. High glucose-induced human umbilical vein vascular endothelial cells (HUVECs) were then treated with drug-containing serum collected from the rats. In high glucose-treated HUVECs, AM-AS combination increased cell viability (P < 0.05), decreased the percentage of apoptotic cells (P < 0.05) and the expression of the proapoptosis protein caspase 3 (P < 0.05), reduced the proportion of cells in the G0/G1 phase (P < 0.05), decreased reactive oxygen species level (P < 0.05), enhanced cell migration and invasion (P < 0.05), and reduced the level of 8-iso-prostaglandin F2alpha. These results indicate that AM-AS combination at the ratio of 3 : 2 ameliorated HUVEC dysfunction by regulating apoptosis, cell migration, and invasion, which might be mediated by their regulatory effect on reactive oxygen species production. The current study provides a theoretical basis for the treatment of diabetic macroangiopathy using AM-AS.

17.
Front Immunol ; 11: 1598, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793232

RESUMO

Epithelial-mesenchymal transition (EMT) is essential in asthma airway remodeling. IL-33 from epithelial cells is involved in pulmonary fibrosis. CD146 has been extensively explored in cancer-associated EMT. Whether IL-33 regulates CD146 in the EMT process associated with asthma airway remodeling is still largely unknown. We hypothesized that EMT in airway remodeling was regulated by the IL-33/CD146 axis. House dust mite (HDM) extract increased the expression of IL-33 and CD146 in epithelial cells. Increased expression of CD146 in HDM-treated epithelial cells could be blocked with an ST2-neutralizing antibody. Moreover, HDM-induced EMT was dependent on the CD146 and TGF-ß/SMAD-3 signaling pathways. IL-33 deficiency decreased CD146 expression and alleviated asthma severity. Similarly, CD146 deficiency mitigated EMT and airway remodeling in a murine model of chronic allergic airway inflammation. Furthermore, CD146 expression was significantly elevated in asthma patients. We concluded that IL-33 from HDM extract-treated alveolar epithelial cells stimulated CD146 expression, promoting EMT in airway remodeling in chronic allergic inflammation.


Assuntos
Remodelação das Vias Aéreas , Asma/metabolismo , Asma/patologia , Transição Epitelial-Mesenquimal , Interleucina-33/metabolismo , Alérgenos/imunologia , Células Epiteliais Alveolares/metabolismo , Animais , Asma/etiologia , Biomarcadores , Antígeno CD146/genética , Antígeno CD146/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Imunofluorescência , Imuno-Histoquímica , Interleucina-33/genética , Camundongos , NF-kappa B/metabolismo , Pyroglyphidae/imunologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Transdução de Sinais
18.
Ann Transl Med ; 8(7): 504, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32395548

RESUMO

Organizing pneumonia (OP) is a distinct clinical and pathologic entity. This condition can be cryptogenic (COP) or secondary to other known causes (secondary OP, SOP). Concomitant occurrence of invasive pulmonary aspergillosis (IPA) with SOP is unusual. Here, we report a case where SOP was a presenting feature in a patient with diagnosed IPA. A previously healthy 62-year-old man presented to the hospital with a month of intermittent fever accompanied by cough and expectoration. According to computed tomography (CT), sputum culture, and transbronchial lung biopsy, he was diagnosed as IPA. Despite undergoing voriconazole and dexamethasone therapy, the patient's condition did not improve after three weeks of therapy. CT-guided percutaneous lung biopsy performed in the left upper lung showed invasive airway aspergillosis with organizing pneumonia. Two months after the combination therapy of voriconazole and methylprednisolone, the CT scan indicated the pulmonary consolidations were almost entirely resolved. To the best of our knowledge, this is the first case of successful non-surgical treatment of IPA with SOP. In a review of the literature, we aimed to highlight the possibility of invasive airway aspergillosis concurrent with secondary organizing pneumonia. Physicians should be aware of the possibility of SOP in the case of IPA.

19.
Int J Mol Med ; 44(3): 847-856, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257467

RESUMO

Oxidized low­density lipoprotein (ox­LDL)­mediated endothelial cell injury has an important role in the vascular complications of type 2 diabetes. Astragaloside IV (ASV) is an active component of Radix Astragali, which has been demonstrated to exert protective effects against endothelial damage. The present study explored whether microRNAs (miRNAs) are involved in mediating the protective effects of ASV on ox­LDL­induced damage in human umbilical vein endothelial cells (HUVECs). RNA sequencing and reverse transcription­quantitative PCR analyses revealed that ox­LDL treatment significantly downregulated miR­140­3p expression in HUVECs. miR­140­3p overexpression promoted cell proliferation and inhibited apoptosis in ox­LDL­induced HUVECs. However, inhibition of miR­140­3p expression could reverse the effects of ASV on ox­LDL­induced HUVECs and reactivate ASV­inhibited PI3K/Akt signaling in ox­LDL­induced HUVECs. In addition, Krüppel­like factor 4 (KLF4) was identified as a target of miR­140­3p in ox­LDL­treated HUVECs. Subsequent experiments revealed that KLF4 overexpression partially counteracted the protective effects of miR­140­3p or ASV treatment in ox­LDL­induced HUVECs. Taken together, the current findings demonstrated that the protective effects of ASV on HUVECs were dependent on miR­140­3p upregulation and subsequent inhibition of KLF4 expression, which in turn suppressed the PI3K/Akt signaling pathway. The present results shed light to the molecular mechanism by which ASV alleviated ox­LDL­induced endothelial cell damage.


Assuntos
Células Endoteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Lipoproteínas LDL/metabolismo , MicroRNAs/genética , Saponinas/farmacologia , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
Sci Rep ; 8(1): 12387, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30120255

RESUMO

The pure, tin (Sn)-doped, lanthanum (La)-doped and Sn/La co-doped titanium dioxide (TiO2) nanomaterials were synthesized using sol-gel method followed by calcination at the temperature of 360 °C, 450 °C and 600 °C, respectively. The structures of the nanomaterials were characterized by X-ray diffraction (XRD), Thermogravimetric (TG), Differential Thermal Analysis (DTA), Scanning Electron Microscopy (SEM), Energy Dispersive Spectrum (EDS), Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectrum (XPS), Diffuse Reflectance Spectrum (DRS), Photoluminescence Spectrum (PL), Brunauer-Emmett-Teller Measurements (BET), respectively. The photocatalytic property of the photocatalysts under UV light was evaluated through the degradation of Rhodamine B (RhB). The results show that the anatase-rutile phase transition is promoted by Sn-doping while La-doping retards the phase transition. However, La doping plays a major role in the process of phase transformation. The photocatalytic activity of pure TiO2 is affected by annealing temperature remarkably and the optimal annealing temperature is 450 °C. The photocatalytic activity of TiO2 is enhanced significantly by Sn and La doping at three different temperatures. Sn/La-TiO2 exhibits the highest degradation rates and the fastest reaction rates probably owing to the synergistic effect of Sn4+ and La3+ ions in inhibiting the recombination of photogenerated electron-hole pairs. The formation of extra surface hydroxyl groups and additional surface area are also beneficial for the photocatalytic activity.

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