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1.
Rapid Commun Mass Spectrom ; 36(1): e9205, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34636119

RESUMO

RATIONALE: Salvianolic acid B (Sal B), the Q-marker in Salvia miltiorrhiza, was proved to present an obvious anti-diabetes effect when treated as a food intake. Until now, the metabolism feature, tissue distribution and anti-diabetes mechanism of Sal B have not been fully elucidated. METHODS: The metabolites of Sal B in rats were profiled using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-diabetes mechanism of Sal B was predicted by network pharmacology. RESULTS: A total of 31 metabolites were characterized in rats after ingestion of Sal B at a dosage of 40 mg/kg, including 1 in plasma, 19 in urine, 31 in feces, 0 in heart, 0 in liver, 0 in spleen, 1 in lung, 1 in kidney and 0 in brain. Among them, 18 metabolites were reported for the first time. Phase I reactions of hydrolysis, hydrogenation, dehydroxylation, hydroxylation, decarboxylation and isomerization, and phase II reactions of methylation were found in Sal B. Notably, decarboxylation and dehydroxylation were revealed in Sal B for the first time. The pharmacology network results showed that Sal B and its metabolites could regulate ALB, PLG, ACE, CASP3, MMP9, MMP2, MTOR, etc. The above targets were involved in insulin signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, etc. CONCLUSIONS: The metabolism feature of Sal B in vivo was systematically revealed, and its anti-diabetes mechanism for further pharmacological validations was predicted based on metabolite profiling and network pharmacology for the first time.

2.
Talanta ; 238(Pt 1): 123037, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34857317

RESUMO

This work describes the unique design of a bidirectional activatable synergetic DNA machine (BAS-DNA machine) for speeded and ultrasensitive determination of microRNA-21 (miR-21), a well-known biomarker for biomedical research and early diagnosis of lung cancer. The BAS-DNA machine is composed by a pair of track strands (Track 1 and Track 2) encoding with two regions in the opposite direction for miR-21 recognition. Introduction of miR-21 can hybridize either with Track 1 or with Track 2 to activate the BAS-DNA machine with a synergistic effect for speeded amplifying the fluorescence signal. Moreover, compared with common DNA machine with only one switch for exogenous target recognition, the BAS-DNA machine with two switches for miR-21 binding allows the speeded and strong operation of the autonomous strand scission, replication, and displacement on Track 1 and Track 2 simultaneously. This behavior makes the BAS-DNA machine powerful for ultrasensitive, specific, and fast screening of miR-21 even from real biological samples, and the fluorescence signal was found to be linear from 1 pM to 10 nM with a detection limit of 703.6 fM. We envision this BAS-DNA machine with its superior assay performance will provide a new avenue for simple, sensitive, and affordable biomedical assays.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Bioensaio , DNA/genética , Limite de Detecção , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico
3.
Mod Pathol ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873305

RESUMO

Acinic cell carcinoma (AiCC) in the nasal cavity and paranasal sinuses has rarely been reported in literature. A recent study demonstrated that recurrent genomic rearrangement [t(4;9) (q13;q31)] is a driver event in AiCC of the salivary glands that could promote the upregulation of transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). In the current study, we evaluated the clinicopathological characteristics and expression of NR4A3 in four new cases of sinonasal AiCC. All four patients were men (range, 27-70 years). The tumor involved only the nasal cavity in two patients, while the other two patients showed involvement of both the nasal cavity and ethmoid sinus. Histologically, the tumor displayed a predominantly solid growth pattern and was composed of hematoxyphilic serous-like cells and scattered intercalated duct-like cells. Immunohistochemically, all cases expressed DOG-1. However, staining for mammaglobin, S-100, CA9, and P63 was absent in all patients. All four cases showed positive nuclear staining for NR4A3. In contrast, none of the other 39 sinonasal tumors, including secretory carcinomas, pleomorphic adenomas, mucoepidermoid carcinomas, adenoid cystic carcinomas, renal cell-like adenocarcinomas, intestinal-type adenocarcinomas, non-intestinal-type adenocarcinomas, extraskeletal myxoid chondrosarcoma, and carcinoma ex pleomorphic adenomas, presented with any positive NR4A3 nuclear staining. Additionally, NR4A3 rearrangements were observed in three cases with sinonasal AiCC by fluorescence in situ hybridization, and the expression level of NR4A3 mRNA was significantly increased in sinonasal AiCC compared with that in normal parotid tissue. Our study demonstrated that sinonasal AiCCs are characterized by an indolent nature and histopathological similarity to parotid AiCCs. Moreover, NR4A3 is a reliable biomarker for distinguishing sinonasal AiCCs from other sinonasal carcinomas.

4.
J Int Med Res ; 49(12): 3000605211067684, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34939435

RESUMO

A Hoffa fracture is a rare intra-articular injury consisting of a coronal plane fracture of one or both of the distal femoral condyles. Because of the rarity of medial Hoffa fractures, only a few reports have described this injury and its arthroscopic management. In this article, we present a rare case involving a 32-year-old man with a displaced medial Hoffa fracture associated with a proximal anterior cruciate ligament tear. He was treated by a single-stage fully all-inside arthroscopic technique. Arthroscopic-assisted internal fixation ensured fragment stability and enabled us to visualize the fracture reduction, monitor the screw insertion, and reconstruct the anterior cruciate ligament tear at the same time. This technique is a novel but demanding treatment method for medial Hoffa fractures and is particularly useful for properly selected patients with associated intra-articular knee injuries.


Assuntos
Lesões do Ligamento Cruzado Anterior , Fraturas do Fêmur , Traumatismos do Joelho , Adulto , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Parafusos Ósseos , Fixação Interna de Fraturas , Humanos , Traumatismos do Joelho/diagnóstico por imagem , Traumatismos do Joelho/cirurgia , Masculino
5.
Sci Total Environ ; : 151417, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34742981

RESUMO

Microalgae cultivation with wastewater could realize the advanced water treatment and pollutant conversion to biomass. Attached microalgae cultivation mode, that can avoid the high-cost and energy-extensive consumption process of biomass recovery from water in suspended cultivation mode, is getting increasing attention. During the attached cultivation, light and nutrient concentration in the internal biofilm, play a direct and crucial role in regulating the growth of microalgae. Hence, the distribution of light and nutrients at different depths of biofilm were first explored in this study together with the change rules of its internal distribution under different external nutrient levels. It demonstrated that the gross growth rate was enhanced by increasing the external nutrient level. Seen from the internal sight of biofilm, the internal nutrient level had a positive response to the external nutrient change. Nutrients (especially nitrogen) distributed homogeneously through the biofilm, and no serious nutrient starvation occurred at the surface layer of biofilm. Photosynthesis rate linearly decreased along the depth of microalgae biofilm (10-120 µm). In conclusion, light, rather than nutrient, would be the key influencing factor on attached microalgae growth. How to optimize the internal light distribution would determine the wastewater purification efficiency based on attached microalgae cultivation.

6.
Water Res ; 206: 117764, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34688094

RESUMO

The anaerobic ammonium oxidation (anammox) process is an autotrophic nitrogen removal process with great potential as a cost-effective and highly efficient technology in the wastewater treatment field. The main challenges yet to be overcome in this new frontier technology are operating at lower temperatures and achieving a high and stable nitrogen removal efficiency. In this study, an up-flow expanded bed reactor with hydroxyapatite (HAP)-anammox granules was operated for more than 200 days at 7°C. The nitrogen loading rate (NLR) was improved from 1.0 g-N/L/d to 3.6 g-N/L/d, together with a high-level nitrogen removal efficiency of 84-92%, which is the highest to date at extremely low temperatures in a continuous experiment. Candidatus Kuenenia was revealed to be the only dominant anammox genus, with a relative abundance of 35.3-37.5%. The optimal operational temperature was around 35°C and the apparent activation energy (Ea) was calculated as 78.37 kJ/mol. The three-layers architecture and architectural evolution of HAP-anammox granules into HAP-cores and peeling biofilms with outstanding settling performance were characterized. Under 7°C, the high capacity of nitrogen removal with robust removal efficiency using HAP-anammox granules was achieved.


Assuntos
Compostos de Amônio , Nitrogênio , Anaerobiose , Reatores Biológicos , Desnitrificação , Durapatita , Oxirredução , Esgotos , Águas Residuárias
7.
Cancer Sci ; 112(11): 4515-4525, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34490691

RESUMO

We aimed to identify whether Rho GTPase activating proteins (RhoGAPs) were downregulated in cervical cancers and might be targeted to reduce the growth of cervical cancer using the GEO database and immunohistochemical analysis to identified changes in transcription and protein levels. We analyzed their proliferation, clone formation ability, and their growth as subcutaneous tumors in mice. To detect ARHGAP30 localization in cells, immunofluorescence assays were conducted. Mass spectrometry combined with immunoprecipitation experiments were used to identify binding proteins. Protein interactions were validated with co-immunoprecipitation assays. Western-blot and q-PCR were applied to analyze candidate binding proteins that were associated with ribosome biogenesis. Puromycin incorporation assay was used to detect the global protein synthesis rate. We identified that ARHGAP30 was the only downregulated RhoGAP and was related to the survival of cervical cancer patients. Overexpression of ARHGAP30 in cervical cancer cells inhibited cell proliferation and migration. ARHGAP30 immunoprecipitated proteins were enriched in the ribosome biogenesis process. ARHGAP30 was located in the nucleous and interacted with nucleolin (NCL). Overexpression of ARHGAP30 inhibited rRNA synthesis and global protein synthesis. ARHGAP30 overexpression induced the ubiquitination of NCL and decreased its protein level in Hela cells. The function of ARHGAP30 on cervical cancer cell ribosome biogenesis and proliferation was independent of its RhoGAP activity as assessed with a RhoGAP-deficient plasmid of ARHGAP30R55A . Overall, the findings revealed that ARHGAP30 was frequently downregulated and associated with shorter survival of cervical cancer patients. ARHGAP30 may suppress growth of cervical cancer by reducing ribosome biogenesis and protein synthesis through promoting ubiquitination of NCL.


Assuntos
Proliferação de Células , Proteínas Ativadoras de GTPase/metabolismo , Ribossomos/metabolismo , Neoplasias do Colo do Útero/metabolismo , Animais , Linhagem Celular Tumoral , Nucléolo Celular/metabolismo , Regulação para Baixo , Feminino , Células HeLa , Humanos , Imunoprecipitação , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Fosfoproteínas/metabolismo , Biossíntese de Proteínas , RNA Ribossômico/biossíntese , Proteínas de Ligação a RNA/metabolismo , Ensaio Tumoral de Célula-Tronco , Ubiquitinação , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
8.
Cell Death Discov ; 7(1): 224, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34455417

RESUMO

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.

9.
Cancer Med ; 10(17): 6010-6021, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34268882

RESUMO

Invasion and metastasis are the main causes of colorectal cancer (CRC)-related death. Accumulating evidence suggested that sphingosine kinase 1 (SphK1) promoted the metastasis of CRC and autophagy played an important role in SphK1 promoting the metastasis of malignancy. However, the mechanism by which SphK1-driven autophagy promotes invasion and metastasis in CRC remains to be clarified. In the present study, immunohistochemical detection showed the expression of SphK1 and paxillin was higher in human CRC tissues than those of normal colorectal mucosal tissues, they were both associated with TNM staging, lymphatic, and distance metastasis. In addition, study of in situ tumor transplantation model in nude mice showed that the suppression of SphK1 inhibited the growth of colonic orthotopic implantation tumors and the expression of paxillin, p-paxillin, LC3 in the tumor. So, SphK1 may promote CRC metastasis via inducing the expression of paxillin expression and its phosphorylation, in vivo. Furthermore, results of CCK8 assay, transwell and wound healing assays showed that SphK1 promoted the viability, invasion, and metastasis of CRC cells. Transmission electron microscopy detection showed that SphK1 is the key factor in autophagy induction in CRC cells. Moreover, western blot examination indicated that the expression of LC3Ⅱ/Ⅰ, paxillin, p-paxillin, MMP-2, and vimentin was enhanced in SphK1-overexpressed CRC cells and suppressed in SphK1 knockdown CRC cells, meanwhile, the expression of E-cadherin was suppressed in SphK1-overexpressed CRC cells and enhanced in SphK1 knockdown CRC cells. Suppression of autophagy by 3MA reversed the expression of paxillin and its phosphorylation in SphK1-overexpressed CRC cells, indicated that SphK1-driven autophagy induced the expression of paxillin and its phosphorylation in CRC cells. Together, these findings reveal that SphK1-driven autophagy may promote the invasion and metastasis of CRC via promoting the expression of focal adhesion paxillin and its phosphorylation.

10.
Comput Biol Med ; 136: 104678, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34329864

RESUMO

Alzheimer's Disease (AD) is a chronic neurodegenerative disease without effective medications or supplemental treatments. Thus, predicting AD progression is crucial for clinical practice and medical research. Due to limited neuroimaging data, two-dimensional convolutional neural networks (2D CNNs) have been commonly adopted to differentiate among cognitively normal subjects (CN), people with mild cognitive impairment (MCI), and AD patients. Therefore, this paper proposes an ensemble learning (EL) architecture based on 2D CNNs, using a multi-model and multi-slice ensemble. First, the top 11 coronal slices of grey matter density maps for AD versus CN classifications were selected. Second, the discriminator of a generative adversarial network, VGG16, and ResNet50 were trained with the selected slices, and the majority voting scheme was used to merge the multi-slice decisions of each model. Afterwards, those three classifiers were used to construct an ensemble model. Multi-slice ensemble learning was designed to obtain spatial features, while multi-model integration reduced the prediction error rate. Finally, transfer learning was used in domain adaptation to refine those CNNs, moving them from working solely with AD versus CN classifications to being applicable to other tasks. This ensemble approach achieved accuracy values of 90.36%, 77.19%, and 72.36% when classifying AD versus CN, AD versus MCI, and MCI versus CN, respectively. Compared with other state-of-the-art 2D studies, the proposed approach provides an effective, accurate, automatic diagnosis along the AD continuum. This technique may enhance AD diagnostics when the sample size is limited.


Assuntos
Doença de Alzheimer , Pesquisa Biomédica , Doenças Neurodegenerativas , Doença de Alzheimer/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Redes Neurais de Computação
11.
Cell Biol Int ; 45(10): 2140-2149, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34288231

RESUMO

Ovarian cancer (OC) is a common reason for gynecologic cancer death. Standard treatments of OC consist of surgery and chemotherapy. However, chemoresistance should be considered. Exosomal miR-21-5p has been shown to regulate the chemosensitivity of cancer cells through regulating pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1). However, the role of miR-21-5p/PDHA1 in OC is unclear. The levels of miR-21-5p and PDHA1 in clinical samples and cells were investigated. Exosomes derived from SKOV3/cisplatin (SKOV3/DDP) cells (DDP-Exos) were isolated and used to treat SKOV3 cells to test DDP-Exos effects on SKOV3 cells. Extracellular acidification rate and oxygen consumption rate were tested with a Seahorse analyzer. Cell apoptosis was analyzed by a flow cytometer. PDHA1 was overexpressed and miR-21-5p was silenced in SKOV3 cells to study the underlying mechanism of miR-21-5p in OC. Quantitative real-time PCR and immunoblots were applied to measure gene expression at mRNA and protein levels. The levels of PDHA1 in DDP-resistant SKOV3 or tumor tissues were significantly decreased while the levels of miR-21-5p were remarkably upregulated. miR-21-5p in DDP-Exos was sharply increased compared to that of Exos. Data also indicated that DDP-Exos treatment suppressed the sensitivity of SKOV3 cells to DDP and promoted cell viability and glycolysis of SKOV3 cells through inhibiting PDHA1 by exosomal miR-21-5p. miR-21-5p derived from DDP-resistant SKOV3 OC cells promotes glycolysis and inhibits chemosensitivity of its progenitor SKOV3 cells by targeting PDHA1. Our data highlights the important role of miR-21-5p/PDHA1 axis in OC and sheds light on new therapeutic development.

12.
Cell Signal ; 86: 110076, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34245861

RESUMO

Protein disulfide isomerase (PDI), a principal endoplasmic reticulum resident oxidoreductase chaperone, is known to play a role in malignancies. This study aims to explore the molecular mechanism by which PDI regulates endoplasmic reticulum stress and the apoptosis signaling pathway in colorectal cancer (CRC). We determined the expression of PDI in CRC tissues and adjacent normal tissues. Gain- and loss- of function assays were conducted to evaluate the effects of PDI on oxidative stress, endoplasmic reticulum stress, and apoptosis in CRC cells, as reflected by hydrogen peroxide (H2O2) level and the expression of related proteins. PDI protein expression was upregulated in CRC tissues. Small molecule inhibitor of PDI or PDI knockdown reduced CRC cell viability and induced apoptosis. Overexpression of wild-type PDI augmented the viability of CRC cells and inhibited endoplasmic reticulum stress response and apoptosis. Small molecule inhibitor of PDI or PDI knockdown increased intracellular H2O2 level and activated apoptosis signaling pathway, which could be reversed by wild-type PDI restoration. Moreover, the catalytic active site of C-terminal of PDI was found to be indispensable for the regulatory effects of PDI on H2O2 levels, apoptosis and cell viability in CRC cells. Collectively, PDI inhibits endoplasmic reticulum stress and apoptosis of CRC cells through its oxidoreductase activity, thereby promoting the malignancy of CRC.

13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(3): 594-601, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34180206

RESUMO

UK Biobank (UKB) is a forward-looking epidemiological project with over 500, 000 people aged 40 to 69, whose image extension project plans to re-invite 100, 000 participants from UKB to perform multimodal brain magnetic resonance imaging. Large-scale multimodal neuroimaging combined with large amounts of phenotypic and genetic data provides great resources to conduct brain health-related research. This article provides an in-depth overview of UKB in the field of neuroimaging. Firstly, neuroimage collection and imaging-derived phenotypes are summarized. Secondly, typical studies of UKB in neuroimaging areas are introduced, which include cardiovascular risk factors, regulatory factors, brain age prediction, normality, successful and morbid brain aging, environmental and genetic factors, cognitive ability and gender. Lastly, the open challenges and future directions of UKB are discussed. This article has the potential to open up a new research field for the prevention and treatment of neurological diseases.


Assuntos
Bancos de Espécimes Biológicos , Neuroimagem , Encéfalo , Reino Unido
14.
Rapid Commun Mass Spectrom ; 35(18): e9157, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34182613

RESUMO

RATIONALE: Characterizing the functional mechanism of quality control marker (Q-marker) was of great importance in revealing the primary pharmacological mechanism of herbs or the other complex system, and drug-related metabolites always contribute to the pharmacological functions. Cortex Phellodendri was used as a core herb in the treatment of diabetes mellitus (DM). As a Q-marker of Cortex Phellodendri, the role of phellodendrine in DM was still unclear. Thus, the characterization of phellodendrine-related metabolites in vivo and the subsequent induced functional mechanism exerted great importance in elucidating the anti-DM mechanism of Cortex Phellodendri. METHODS: An ultra-high-performance liquid chromatography-coupled time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method was developed to profile metabolites of phellodendrine in rats. The potential pharmacological mechanism against DM was predicted by network pharmacology. RESULTS: A total of 19 phellodendrine-related metabolites were screened out in rats for the first time. Among them, M4, M5, M9, and M12 were regarded as the primary metabolites. Meanwhile, phase I metabolic reactions of hydroxylation, demethylation, and isomerization and phase II reactions of glucuronidation and sulfation occurred to phellodendrine; glucuronidation and hydroxylation were the two main metabolic reactions. Moreover, the potential targets of phellodendrine and three main metabolites (M4, M5, and M12) were predicted by a network pharmacological method, and they mainly shared 52 targets, including PDE5A, CHRNA3, SIGMAR1, F3, ESR1, DRD1, DRD2, DRD3, and DRD4. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that calcium signaling pathway, cGMP-PKG signaling pathway, and cAMP signaling pathway were regarded as the core mechanism of phellodendrine to treat DM. CONCLUSION: The metabolic feature of phellodendrine in vivo was revealed for the first time, and its anti-DM mechanism information for further pharmacological validations was also supplied. It also gave a direction to further elucidation of pharmacological mechanism of Cortex Phellodendri in treating DM.

15.
Cancer Cell Int ; 21(1): 320, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174897

RESUMO

BACKGROUND: Rho GTPase activating protein 10 (ARHGAP10) has been implicated as an essential element in multiple cellular process, including cell migration, adhesion and actin cytoskeleton dynamic reorganization. However, the correlation of ARHGAP10 expression with epithelial-mesenchymal transition (EMT) in lung cancer cells is unclear and remains to be elucidated. Herein, we investigated the relationship between the trait of ARHGAP10 and non-small cell lung cancer (NSCLC) pathological process. METHODS: Immunohistochemistry was conducted to evaluate the expression of ARHGAP10 in NSCLC tissues. CCK-8 assays, Transwell assays, scratch assays were applied to assess cell proliferation, invasion and migration. The expression levels of EMT biomarkers and active molecules involved in PI3K/Akt/GSK3ß signaling pathway were examined through immunofluorescence and Western blot. RESULTS: ARHGAP10 was detected to be lower expression in NSCLC tissues compared with normal tissues from individuals. Moreover, overexpression of ARHGAP10 inhibited migratory and invasive potentials of A549 and NCI-H1299 cells. In addition, ARHGAP10 directly mediated the process of EMT via PI3K/Akt/GSK3ß pathway. Meanwhile, activation of the signaling pathway of insulin-like growth factors-1 (IGF-1) reversed ARHGAP10 overexpression regulated EMT in NSCLC cells. CONCLUSION: ARHGAP10 inhibits the epithelial-mesenchymal transition in NSCLC via PI3K/Akt/GSK3ß signaling pathway, suggesting agonist of ARHGAP10 may be an optional remedy for NSCLC patients than traditional opioids.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34067784

RESUMO

Homeless individuals have many negative experiences with inequality regarding access to and the use of primary healthcare services, so policies to eliminate the disparities in and barriers to primary care access for these people are needed. The aim of this study was to explore the use and determinants of free hospital outpatient services for homeless people, in order to describe the provision of free healthcare policies for this vulnerable population in Taipei. One cross-sectional survey was conducted to recruit homeless people aged 45 years old and over in Taipei in 2018. A structured questionnaire was used, and face-to-face interviews were conducted by three social workers to collect the data. Finally, 129 participants were recruited in the study. The results show that 81.4% of the homeless people had made free hospital outpatient care visits (mean = 5.9 visits) in the last three months. An unadjusted logistic regression analysis showed that those homeless people who reported having usual healthcare providers, with higher depressive symptom scores, who used medication and had been hospitalized within one year, and had more chronic diseases, were significantly more likely to make free hospital outpatient visits. The adjusted logistic regression model indicates that homeless people with severe depressive symptoms (odds ratio (OR) = 9.32, 95% CI = 1.15-56.07), who had received medication (OR = 3.93; 95% CI = 1.06-14.52), and who had more than five chronic diseases (OR = 1.06, 95% CI = 1.35-13.27), were significantly more likely to make free hospital outpatient visits than their counterparts. The findings highlight that homeless people have higher healthcare requirements than the general population, and the healthcare system should pay more attention to factors associated with higher outpatient service use, such as homelessness, severe depressive symptoms, the receipt of medication and chronic diseases.


Assuntos
Pessoas em Situação de Rua , Pacientes Ambulatoriais , Adulto , Idoso , Assistência Ambulatorial , Estudos Transversais , Hospitais , Humanos , Pessoa de Meia-Idade
17.
Emerg Microbes Infect ; 10(1): 1309-1319, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33792531

RESUMO

The epidemic Streptococcus suis (S. suis) strain [Sequence type (ST) 7] was gradually evolving from the non-epidemic ST1 strain and got the ability for high expressing of suilysin (SLY). And the high expression of SLY was required for the epidemic strain to cause NLRP3 hyperactivation, which is essential for the induction of cytokines storm, dysfunction of multiple organs, and a high incidence of mortality, the characters of streptococcal toxic shock-like syndrome (STSLS). However, it remains to be elucidated whether acquiring high SLY expression due to genome evolution was sufficient for the non-epidemic strain to cause STSLS. Here, we found that the overexpression of SLY in ST1 strain (P1/7-SLY) could obviously increase the inflammasome activation, which was dependent on NLRP3 signalling. In contrast, the strain (P1/7-mSLY) overexpressing the mutant SLY (protein without hemolytic activity) could not significantly increase the inflammasome activation. Furthermore, similar to the epidemic strain, P1/7-SLY could cause STSLS in nlrp3+/+ mice but not in nlrp3-/- mice. In contrast, P1/7-mSLY could not cause STSLS in both nlrp3 +/+ mice and nlrp3-/- mice. In summary, we demonstrate that genetic evolution enabling S. suis strain to express high level of SLY may be an essential and sufficient condition for NLRP3 inflammasome hyperactivation, which could further cause cytokines storm and STSLS.


Assuntos
Proteínas Hemolisinas/genética , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Choque Séptico/imunologia , Infecções Estreptocócicas/imunologia , Streptococcus suis/patogenicidade , Animais , Síndrome da Liberação de Citocina/imunologia , Evolução Molecular , Expressão Gênica , Proteínas Hemolisinas/metabolismo , Hemólise , Humanos , Inflamassomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Monócitos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Choque Séptico/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus suis/genética , Streptococcus suis/metabolismo , Células THP-1
18.
Food Funct ; 12(10): 4325-4336, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33876806

RESUMO

Food additives are widely used in our daily life, and the side-effects caused by them have gained extensive attention around the world. Notably, constituent-oriented metabolites, in some sense, always contribute to pharmacological changes, inducing toxicity, therapeutic effects, etc. Characterization of the metabolites and their potential functions is of great importance to the practical applications. In this work, an integrated strategy by combining metabolite profiling and network pharmacology was applied to characterize the metabolic features and reveal pharmacological changes of neohesperidin dihydrochalcone (NHDC) in vivo to demonstrate its pharmacological mechanism and potential functions. As a result, a total of 19 metabolites (3 in plasma, 19 in urine, 8 in feces, 3 in heart, 5 in liver, 0 in spleen, 1 in lung, 2 in kidneys and 2 in brain) were screened and 18 of them were characterized for the first time. Phase I metabolic reactions of hydrolysis and phase II reactions of glucuronidation, sulfation, glutamylation, N-butyryl glycylation and lactylation were the main metabolic reactions of NHDC in vivo. Moreover, the results analyzed by network pharmacology revealed that, in addition to common pathways (steroid hormone biosynthesis) of NHDC, metabolites' targets were involved in pathways in cancer, ovarian steroidogenesis, proteoglycans in cancer, PI3K-Akt signaling pathway and progesterone-mediated oocyte maturation, indicating that these functional changes might result in potential novel functions or other side-effects, such as a disorder of steroid hormones. Our work provided the metabolic features and functional modifications of NHDC in vivo for the first time, and meaningful information for further pharmacological validations or potential functions is supplied.


Assuntos
Chalconas/farmacologia , Dissecação/métodos , Aditivos Alimentares/farmacologia , Hesperidina/análogos & derivados , Animais , Chalconas/sangue , Chalconas/urina , Modelos Animais de Doenças , Hesperidina/sangue , Hesperidina/farmacologia , Hesperidina/urina , Fígado/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
19.
World J Gastroenterol ; 27(14): 1507-1523, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33911471

RESUMO

BACKGROUND: Whether to use a T-tube for biliary anastomosis during orthotopic liver transplantation (OLT) remains a debatable question. Some surgeons chose to use a T-tube because they believed that it reduces the incidence of biliary strictures. Advances in surgical techniques during the last decades have significantly decreased the overall incidence of postoperative biliary complications. Whether using a T-tube during OLT is still associated with the reduced incidence of biliary strictures needs to be re-evaluated. AIM: To provide an updated systematic review and meta-analysis on using a T-tube during adult OLT. METHODS: In the electronic databases MEDLINE, PubMed, Scopus, ClinicalTrials.gov, the Cochrane Library, the Cochrane Hepato-Biliary Group Controlled Trails Register, and the Cochrane Central Register of Controlled Trials, we identified 17 studies (eight randomized controlled trials and nine comparative studies) from January 1995 to October 2020. The data of the studies before and after 2010 were separately extracted. We chose the overall biliary complications, bile leaks or fistulas, biliary strictures (anastomotic or non-anastomotic), and cholangitis as outcomes. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to describe the results of the outcomes. Furthermore, the test for overall effect (Z) was used to test the difference between OR and 1, where P ≤ 0.05 indicated a significant difference between OR value and 1. RESULTS: A total of 1053 subjects before 2010 and 1346 subjects after 2010 were included in this meta-analysis. The pooled results showed that using a T-tube reduced the incidence of postoperative biliary strictures in studies before 2010 (P = 0.012, OR = 0.62, 95%CI: 0.42-0.90), while the same benefit was not seen in studies after 2010 (P = 0.60, OR = 0.76, 95%CI: 0.27-2.12). No significant difference in the incidence of overall biliary complications (P = 0.37, OR = 1.41, 95%CI: 0.66-2.98), bile leaks (P = 0.89, OR = 1.04, 95%CI: 0.63-1.70), and cholangitis (P = 0.27, OR = 2.00, 95%CI: 0.59-6.84) was observed between using and not using a T-tube before 2010. However, using a T-tube appeared to increase the incidence of overall biliary complications (P = 0.049, OR = 1.49, 95%CI: 1.00-2.22), bile leaks (P = 0.048, OR = 1.91, 95%CI: 1.01-3.64), and cholangitis (P = 0.02, OR = 7.21, 95%CI: 1.37-38.00) after 2010. A random-effects model was used in biliary strictures (after 2010), overall biliary complications (before 2010), and cholangitis (before 2010) due to their heterogeneity (I 2 = 62.3%, 85.4%, and 53.6%, respectively). In the sensitivity analysis (only RCTs included), bile leak (P = 0.66) lost the significance after 2010 and a random-effects model was used in overall biliary complications (before 2010), cholangitis (before 2010), bile leaks (after 2010), and biliary strictures (after 2010) because of their heterogeneity (I 2 = 92.2%, 65.6%, 50.9%, and 80.3%, respectively). CONCLUSION: In conclusion, the evidence gathered in our updated meta-analysis showed that the studies published in the last decade did not provide enough evidence to support the routine use of T-tube in adults during OLT.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Sistema Biliar , Transplante de Fígado , Procedimentos Cirúrgicos Reconstrutivos , Adulto , Anastomose Cirúrgica , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Humanos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
20.
Brain Sci ; 11(2)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672406

RESUMO

Alzheimer's disease (AD) is a disease of a heterogeneous nature, which can be disentangled by exploring the characteristics of each AD subtype in the brain structure, neuropathology, and cognition. In this study, a total of 192 AD and 228 cognitively normal (CN) subjects were obtained from the Alzheimer's disease Neuroimaging Initiative database. Based on the cortical thickness patterns, the mixture of experts method (MOE) was applied to the implicit model spectrum of transforms lined with each AD subtype, then their neuropsychological and neuropathological characteristics were analyzed. Furthermore, the piecewise linear classifiers composed of each AD subtype and CN were resolved, and each subtype was comprehensively explained. The following four distinct AD subtypes were discovered: bilateral parietal, frontal, and temporal atrophy AD subtype (occipital sparing AD subtype (OSAD), 29.2%), left temporal dominant atrophy AD subtype (LTAD, 22.4%), minimal atrophy AD subtype (MAD, 16.1%), and diffuse atrophy AD subtype (DAD, 32.3%). These four subtypes display their own characteristics in atrophy pattern, cognition, and neuropathology. Compared with the previous studies, our study found that some AD subjects showed obvious asymmetrical atrophy in left lateral temporal-parietal cortex, OSAD presented the worst cerebrospinal fluid levels, and MAD had the highest proportions of APOE ε4 and APOE ε2. The subtype characteristics were further revealed from the aspect of the model, making it easier for clinicians to understand. The results offer an effective support for individual diagnosis and prognosis.

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