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1.
Theranostics ; 12(2): 657-674, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976206

RESUMO

Rationale: Corneal neovascularization (CoNV) is a severe complication of various types of corneal diseases, that leads to permanent visual impairment. Current treatments for CoNV, such as steroids or anti-vascular endothelial growth factor agents, are argued over their therapeutic efficacy and adverse effects. Here, we demonstrate that transforming growth factor-ß (TGF-ß)-activated kinase 1 (TAK1) plays an important role in the pathogenesis of CoNV. Methods: Angiogenic activities were assessed in ex vivo and in vitro models subjected to TAK1 inhibition by 5Z-7-oxozeaenol, a selective inhibitor of TAK1. RNA-Seq was used to examine pathways that could be potentially affected by TAK1 inhibition. A gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol was developed as the eyedrop to treat CoNV in a rodent model. Results: We showed that 5Z-7-oxozeaenol reduced angiogenic processes through impeding cell proliferation. Transcriptome analysis suggested 5Z-7-oxozeaenol principally suppresses cell cycle and DNA replication, thereby restraining cell proliferation. In addition, inhibition of TAK1 by 5Z-7-oxozeaenol blocked TNFα-mediated NFκB signalling, and its downstream genes related to angiogenesis and inflammation. 5Z-7-oxozeaenol also ameliorated pro-angiogenic activity, including endothelial migration and tube formation. Furthermore, topical administration of the gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol led to significantly greater suppression of CoNV in a mouse model compared to the free form of 5Z-7-oxozeaenol, likely due to extended retention of 5Z-7-oxozeaenol in the cornea. Conclusion: Our study shows the potential of TAK1 as a therapeutic target for pathological angiogenesis, and the gelatin nanoparticle coupled with 5Z-7-oxozeaenol as a promising new eyedrop administration model in treatment of CoNV.

3.
Microb Biotechnol ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35006649

RESUMO

3, 4-Dihydroxyphenyl-l-alanine (l-DOPA) is a compound of high medical value and is considered effective as a treatment for Parkinson's disease. Currently, bioproduction of l-DOPA is mainly carried out by whole-cell catalysis mediated by recombinant Escherichia coli carrying heterogeneous tyrosine phenol lyase. Vibrio natriegens is increasingly attracting attention owing to its superiority, including extremely rapid growth and high soluble protein expression capacity. In this study, we attempt to develop an efficient whole-cell catalyst for l-DOPA production using V. natriegens as the chassis. The maximum soluble protein expression by V. natriegens was accomplished in 4 h at 37°C, which was equivalent to that achieved by E. coli in 16 h at 16°C. Furthermore, the maximum productivity reached over 10.0 g l-1 h-1 in the early stage of biocatalysis, nearly two-fold higher than previously reported. Approximately 54.0 g l-1 l-DOPA was obtained with a catechol conversion rate greater than 95%. In conclusion, V. natriegens displays advantages, including rapid protein expression and catalytic rate in the catalysis process for l-DOPA production. These findings strongly suggest that V. natriegens has remarkable potential as a whole-cell catalysis chassis for the production of valuable chemicals.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35020152

RESUMO

Cadmium (Cd) pollution is a serious heavy metal pollution in paddy fields, but its effect and underlying mechanism on soil arthropod overwintering and cold resistance are still unclear. In the present study, adult females of the wolf spider Pirata subpiraticus exposed to Cd stress underwent a simulated temperature process (25℃ → 16℃ → 8℃ → 4℃). The mortality rate and content of nutrients in the Cd-treated spiders were dramatically elevated after low-temperature treatment compared to those in the Cd-free control spiders under the same temperature condition. To uncover the putative modulatory mechanism of Cd on cold tolerance in P. subpiraticus, we employed an in-depth RNA sequencing analysis and yielded a total of 888 differentially expressed genes (DEGs). Besides, we characterized genes that participate in multiple cryoprotectant syntheses, including arginine, cysteine, glucose, glycerol, heat shock protein, and mannose. The enrichment analyses found that most of the DEGs involved in biological processes and pathways were related to carbohydrate, lipid, and protein metabolism. Notably, ten Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as starch and sucrose metabolism, arachidonic acid metabolism, amino acid metabolism, mineral absorption, and vitamin digestion and absorption, were distinctively enriched with downregulated genes. Meanwhile, we also identified that seven DEGs might inhibit the KEGG pathway of ovarian steroidogenesis and potentially cripple ovarian function and fecundity in the spider. The decreased egg sac weight, number of hatched spiderlings, and vitellin concentration further supported the view that Cd exposure vitiates the overwintering spider's fecundity. Collectively, the comparative analysis provides a novel perspective regarding the survival response and fecundity on the cold tolerance of spiders under Cd stress and offers a profound insight for evaluating Cd-induced toxicity on overwintering arthropods.

5.
Brain Res ; : 147779, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007546

RESUMO

Pain can be ignited by noxious chemical (e.g., acid), mechanical (e.g., pressure), and thermal (e.g., heat) stimuli and generated by the activation of sensory neurons and their axonal terminals called nociceptors in the periphery. Nociceptive information transmitted from the periphery is projected to the central nervous system (thalamus, somatosensory cortex, insular, anterior cingulate cortex, amygdala, periaqueductal grey, prefrontal cortex, etc.) to generate a unified experience of pain. Local field potential (LFP) recording is one of the neurophysiological tools to investigate the combined neuronal activity, ranging from several hundred micrometers to a few millimeters (radius), located around the embedded electrode. The advantage of recording LFP is that it provides stable simultaneous activities in various brain regions in response to external stimuli. In this study, differential LFP activities from the contralateral anterior cingulate cortex (ACC), ventral tegmental area (VTA), and bilateral amygdala in response to peripheral noxious formalin injection were recorded in anesthetized male rats. The results indicated increased power of delta, theta, alpha, beta, and gamma bands in the ACC and amygdala but no change of gamma-band in the right amygdala. Within the VTA, intensities of the delta, theta, and beta bands were only enhanced significantly after formalin injection. It was found that the connectivity (i.t. the coherence) among these brain regions reduced significantly under the formalin-induced nociception, which suggests a significant interruption within the brain. With further study, it will sort out the key combination of structures that will serve as the signature for pain state.

6.
Vet Microbiol ; 264: 109303, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34923246

RESUMO

In this study, whether H9N2 influenza A virus (IAV) infection contributed to secondary Klebsiella pneumoniae infection was investigated. From post-infection onwards, clinical symptoms were monitored, examined and recorded daily for 11 days. As a result, no clinical signs were observed in the mice infected with single H9N2 IAV, implying that H9N2 IAV was less pathogenic to mice. Compared to single K. pneumonia infection, K. pneumoniae infection following H9N2 IAV infection exacerbates lung histopathological lesions and apoptosis, resulting in more severe diseases. Lung index of the mice with H9N2 IAV and K. pneumoniae co-infection was significantly higher than those in the other groups. Bacterial loads in the tissues in H9N2 IAV and K. pneumoniae co-infection group were significantly higher than those in the single K. pneumoniae infection group at 7 dpi. It demonstrated that prior H9N2 IAV infection contributed to K. pneumonia proliferation and delayed bacterial clearance in mice. Secondary K. pneumoniae infection influences seroconversion of anti-H9N2 antibody titers and the cytokine profiles. The findings demonstrated that H9N2 IAV infection facilitated secondary K. pneumonia infection, causing severe the diseases in mice.


Assuntos
Vírus da Influenza A Subtipo H9N2 , Klebsiella pneumoniae , Infecções por Orthomyxoviridae , Pneumonia , Animais , Coinfecção , Vírus da Influenza A Subtipo H9N2/fisiologia , Klebsiella pneumoniae/fisiologia , Camundongos , Infecções por Orthomyxoviridae/microbiologia , Infecções por Orthomyxoviridae/virologia , Pneumonia/microbiologia , Pneumonia/virologia
7.
Ann Clin Microbiol Antimicrob ; 20(1): 80, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876146

RESUMO

BACKGROUND: BlaAFM-1 (GenBank Accession No. 143105.1) is a new B1 subclass metallo-ß-lactamase gene discovered by our group, and isolated from an Alcaligenes faecalis plasmid that renders carbapenem antibiotics ineffective. In this study, we generated a fast and reliable assay for blaAFM-1 detection. METHODS: We designed optimum loop-mediated isothermal amplification (LAMP) primers and constructed a recombinant plasmid AFM-1 to specifically detect blaAFM-1. Optimal LAMP primers were used to assess sensitivity of the recombinant plasmid AFM-1 and blaAFM-1-supplemented samples (simulated sputum and simulated feces). Fifty two samples, without blaAFM-1, were used to assess LAMP real-time assay specificity; these samples were verified by conventional PCR and sequencing for the absence of blaAFM-1. Three hundred clinical Gram-negative carbapenem-resistant strains were tested by LAMP assay for strains carrying blaAFM-1, which were confirmed by conventional PCR and Sanger sequencing. We calculated the sensitivity and its 95% confidence interval (95% CI), specificity and its 95% CI, and predictive values of the LAMP assay and conventional PCR/sequencing by investigating positive and negative clinical strains. RESULTS: The lowest limit of detection for the recombinant plasmid AFM-1 and blaAFM-1-supplemented samples (in both simulated sputum and simulated feces) was 101 copies/reaction. All amplification curves of the 52 blaAFM-1-free bacteria strains were negative, suggesting the LAMP assay had excellent specificity for detecting blaAFM-1. Among the 300 clinical strains, eight were positive for blaAFM-1 using LAMP. These LAMP results were consistent with conventional PCR and Sanger sequencing data. As with conventional PCR/sequencing, the LAMP method exhibits 100% sensitivity (95% CI 59.8-100%) and 100% specificity (95% CI 98.4-100%) for blaAFM-1 detection. The LAMP assay is also time-efficient (1 h) for blaAFM-1 detection. CONCLUSIONS: We established a new LAMP assay with high sensitivity and specificity to detect the novel B1-ß-lactamase gene, blaAFM-1.

8.
Front Cell Dev Biol ; 9: 771773, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869369

RESUMO

The generation of blood cells in a significant amount for clinical uses is still challenging. Human pluripotent stem cells-derived hemopoietic cells (hPSC-HCs) are a promising cell source to generate blood cells. Previously, it has been shown that the attached substrates are crucial in the maintenance or differentiation of hPSCs. In this study, a new family of artificial extracellular matrix (ECM) called colloidal self-assembled patterns (cSAPs: #1-#5) was used for the expansion of mouse and human PSCs. The optimized cSAP (i.e., #4 and #5) was selected for subsequent hemopoietic differentiation of human embryonic stem cells (hESCs). Results showed that the hematopoietic potential of hESCs was enhanced approx 3-4 folds on cSAP #5 compared to the flat control. The cell population of hematopoietic progenitors (i.e., CD34+CD43+ cells) and erythroid progenitors (i.e., CD71+GPA+ cells) were enhanced 4 folds at day 8 and 3 folds at day 14. RNA sequencing analysis of cSAP-derived hESCs showed that there were 300 genes up-regulated and 627 genes down-regulated compared to the flat control. The enriched signaling pathways, including up-regulation (i.e., Toll-like receptor, HIF-1a, and Notch) or down-regulation (i.e., FAs, MAPK, JAK/STAT, and TGF-ß) were classic in the maintenance of hESC phenotype Real time PCR confirmed that the expression of focal adhesion (PTK2, VCL, and CXCL14) and MAPK signaling (CAV1) related genes was down-regulated 2-3 folds compared to the flat control. Altogether, cSAP enhances the pluripotency and the hematopoietic potential of hESCs that subsequently generates more blood-like cells. This study reveals the potential of cSAPs on the expansion and early-stage blood cell lineage differentiation of hPSCs.

9.
Anal Chem ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34879197

RESUMO

In recent years, the combination of DNA nanotechnology and biosensing has been extensively reported. Herein, we attempted to develop a dual sensitization smartphone colorimetric strategy based on rolling circle amplification (RCA) coils gathering Au tetrahedra and explore its application. The dual sensitization effect of this strategy was achieved by rolling circle amplification (RCA) and Au tetrahedra. Under the initiation of the complementary DNA, a large number of ssDNA were generated, achieving amplification of the reaction signal. At the same time, due to the formation of Au tetrahedra, more gold nanoparticles could be gathered under the same conditions, and the signal would be amplified again. Using software ImageJ, the gray value of the reaction solution can be analyzed, detecting the target timely under the practical conditions of lack of equipment. By selecting aptamers with strong binding affinity, we applied this strategy to detect creatine kinase isoenzymes (CK-MB), showing a limit of detection of 0.8 pM, which performed well in actual detection and can meet the needs for real-time detection of CK-MB. Therefore, a universal detection platform was developed, which has broad application prospects in biosensing, clinical diagnosis, food detection, and other fields.

10.
Cancers (Basel) ; 13(23)2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34885184

RESUMO

The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.

11.
Front Bioeng Biotechnol ; 9: 738081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858956

RESUMO

Globally, about two million people die from liver diseases every year. Liver transplantation is the only reliable therapy for severe end-stage liver disease, however, the shortage of organ donors is a huge limitation. Human hepatocytes derived liver progenitor-like cells (HepLPCs) have been reported as a novel source of liver cells for development of in vitro models, cell therapies, and tissue-engineering applications, but their functionality as transplantation donors is unclear. Here, a 3-dimensional (3D) co-culture system using HepLPCs and human umbilical vein endothelial cells (HUVECs) was developed. These HepLPC spheroids mimicked the cellular interactions and architecture of mature hepatocytes, as confirmed through ultrastructure morphology, gene expression profile and functional assays. HepLPCs encapsulated in alginate beads are able to mitigate liver injury in mice treated with carbon tetrachloride (CCL4), while alginate coating protects the cells from immune attack. We confirmed these phenomena due to HUVECs producing glial cell line-derived neurotrophic factor (GDNF) to promote HepLPCs maturation and enhance HepLPCs tight junction through MET phosphorylation. Our results display the efficacy and safety of the alginate microencapsulated spheroids in animal model with acute liver injury (ALF), which may suggest a new strategy for cell therapy.

12.
J Hypertens ; 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34889864

RESUMO

BACKGROUND: In patients with stable coronary artery disease, low DBP is associated with an increased risk of myocardial infarction and cardiovascular death, but its association with clinical outcomes in patients with acute myocardial infarction undergoing percutaneous coronary intervention (PCI) is unknown. METHODS: Consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI from January 2010 to June 2016 were enrolled. The patients were divided into five groups according to the quintiles of DBP at admission. The primary outcome was in-hospital major adverse cardiovascular events (MACE) including all-cause death, stroke, target vessel revascularization, and recurrent myocardial infarction. RESULTS: A total of 2198 patients were enrolled, of whom 157 (7.1%) developed in-hospital MACE. Patients with DBP lower than 60 mmHg was associated with a higher rate of in-hospital MACE (14.8, 7.8, 5.6, 6.1, and 3.8%, P < 0.001) and all-cause death (12.5, 6.4, 4.3, 3.9, and 1.9%, P < 0.001) compared with those with DBP 60-69, 70-79, 80-89, and at least 90 mmHg. Multivariate logistic regression analysis demonstrated that DBP higher than 90 mmHg was a significant predictor of lower risk of in-hospital MACE (OR = 0.16, 95% CI = 0.04-0.61, P = 0.007). Cubic spline models for the association between DBP and MACE did not demonstrate a U-type relationship after adjusting for potential risk factors. During the follow-up, lower DBP was associated with a higher risk of all-cause death (P < 0.0001). CONCLUSION: Lower DBP is independently associated with an elevated risk of in-hospital MACE and follow-up all-cause death.

13.
Med Sci Monit ; 27: e933688, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34907150

RESUMO

BACKGROUND Cryptococcal meningitis (CM) is one of the most common opportunistic neuroinfections in patients with HIV. Most studies have focused on non-HIV CM and there are only a few studies on HIV CM in China. The purpose of the present study was to evaluate the characteristics and risk factors for CM recurrence in patients infected with HIV in the Chongqing Public Health Treatment Center in China. MATERIAL AND METHODS From January 2014 to December 2017, all patients with CM aged 18 years or older were enrolled and a case-control study was performed to determine the risk factors associated with recurrence of CM. Antimicrobial susceptibility was determined with a fungal drug sensitivity kit and the sequence types (STs) were analyzed with multilocus sequence typing. RESULTS The incidence of CM in the 5185 HIV-infected patients was 3.5% (179). Follow-up data were available for 82 of the patients for whom complete medical records were available and they were included in the present study. There were 7 STs among 82 Cryptococcus neoformans isolates; ST5 and ST31 were the most prevalent genotypes. Testing showed that C. neoformans had high sensitivity to 5 antifungal drugs and no differences in resistance were observed, even when different STs were tested. Risk factors for recurrence were analyzed in 69 patients, excluding those who died. The results of multivariate analysis showed that only hospital stay was associated with recurrence of CM. CONCLUSIONS Our results indicated that combining education about medication with clinical treatment could help prevent recurrence of CM.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34935037

RESUMO

OBJECTIVES: Aortic arch type is a readily recognizable and obtainable morphological feature of the aorta that does not require complex measurements. The goal of this study was to evaluate whether aortic arch type is a comparable and alternative morphological parameter for predicting acute type B aortic dissection (aTBAD) by comparing the prognostic value of the aortic arch type with that of other morphological parameters such as aortic length, angulation and tortuosity index. METHODS: The patients with aTBAD (n = 216) were matched 1:1 with a control group (n = 263) by propensity score matching. The morphological data of the ascending aorta and the aortic arch, which included diameter, length, angulation and tortuosity index, were collected on a three-dimensional aortic model using 3mensio Vascular software. The aortic arch type was identified by the vertical distance from the origin of the brachiocephalic trunk to the top of the arch. The binary logistic regression models were analysed to determine the independent geometric variables related to the aTBAD. The nonparametric approach was performed to assess whether there were statistical differences between the area under the receiver operating characteristic curves (AUC) of the models. RESULTS: After propensity score matching, 151 matched pairs of patients were selected. The diameters at the sinotubular junction and the mid-ascending aorta, the ascending aorta length and the ascending aorta angulation in the aTBAD group were significantly greater than those of the controls. Compared with the control group, the diameters at the proximal aortic arch, mid-aortic arch and distal aortic arch, the angulation and the tortuosity index of the aortic arch were significantly greater in the aTBAD group. The proportion of the type III arch in the patients with aTBAD is higher than that of the type I arch and the type II arch (χ2 = 70.187; P < 0.001). Binary logistic regression analysis showed that the diameter at the mid-aortic arch, the ascending aorta length, the aortic arch angulation and the tortuosity index were independently related to the aTBAD with an AUC value of 0.887. Another binary logistic regression analysis indicated that the diameter at the mid-aortic arch and the aortic arch type were independent correlative variables associated with the aTBAD with an AUC of 0.874. No significant difference was observed in the prognostic value of receiver operating characteristic curves between the 2 models (P = 0.716). CONCLUSIONS: The type III arch, which has the characteristics of aortic elongation, incremental angulation and tortuosity index, is a comparable and alternative identifier for patients at high risk for aTBAD.

16.
Front Neurosci ; 15: 733311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34924926

RESUMO

Background: Studies on non-pharmacological strategies for improving gait performance and cognition in Parkinson's disease (PD) are of great significance. We aimed to investigate the effect of and mechanism underlying enriched rehabilitation as a potentially effective strategy for improving gait performance and cognition in early-stage PD. Methods: Forty participants with early-stage PD were randomly assigned to receive 12 weeks (2 h/day, 6 days/week) of enriched rehabilitation (ER; n = 20; mean age, 66.14 ± 4.15 years; 45% men) or conventional rehabilitation (CR; n = 20; mean age 65.32 ± 4.23 years; 50% men). In addition, 20 age-matched healthy volunteers were enrolled as a control (HC) group. We assessed the general motor function using the Unified PD Rating Scale-Part III (UPDRS-III) and gait performance during single-task (ST) and dual-task (DT) conditions pre- and post-intervention. Cognitive function assessments included the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Trail Making Test (TMT), which were conducted pre- and post-intervention. We also investigated alteration in positive resting-state functional connectivity (RSFC) of the left dorsolateral prefrontal cortex (DLPFC) in participants with PD, mediated by ER, using functional magnetic resonance imaging (fMRI). Results: Compared with the HC group, PD participants in both ER and CR groups performed consistently poorer on cognitive and motor assessments. Significant improvements were observed in general motor function as assessed by the UPDRS-III in both ER and CR groups post-intervention. However, only the ER group showed improvements in gait parameters under ST and DT conditions post-intervention. Moreover, ER had a significant effect on cognition, which was reflected in increased MoCA, SDMT, and TMT scores post-intervention. MoCA, SDMT, and TMT scores were significantly different between ER and CR groups post-intervention. The RSFC analysis showed strengthened positive functional connectivity between the left DLPFC and other brain areas including the left insula and left inferior frontal gyrus (LIFG) post-ER. Conclusion: Our findings indicated that ER could serve as a potentially effective therapy for early-stage PD for improving gait performance and cognitive function. The underlying mechanism based on fMRI involved strengthened RSFC between the left DLPFC and other brain areas (e.g., the left insula and LIFG).

17.
Nat Methods ; 18(12): 1515-1523, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34824474

RESUMO

Great advances have been made in mass spectrometric data interpretation for intact glycopeptide analysis. However, accurate identification of intact glycopeptides and modified saccharide units at the site-specific level and with fast speed remains challenging. Here, we present a glycan-first glycopeptide search engine, pGlyco3, to comprehensively analyze intact N- and O-glycopeptides, including glycopeptides with modified saccharide units. A glycan ion-indexing algorithm developed for glycan-first search makes pGlyco3 5-40 times faster than other glycoproteomic search engines without decreasing accuracy or sensitivity. By combining electron-based dissociation spectra, pGlyco3 integrates a dynamic programming-based algorithm termed pGlycoSite for site-specific glycan localization. Our evaluation shows that the site-specific glycan localization probabilities estimated by pGlycoSite are suitable to localize site-specific glycans. With pGlyco3, we confidently identified N-glycopeptides and O-mannose glycopeptides that were extensively modified by ammonia adducts in yeast samples. The freely available pGlyco3 is an accurate and flexible tool that can be used to identify glycopeptides and modified saccharide units.

18.
J Cell Biochem ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825407

RESUMO

Exploiting human mesenchymal stem cells (hMSCs) was proposed as a promising therapeutic approach for cardiovascular disease due to their capacity to differentiate into cardiac cells. Though modulation of the intracellular signaling pathways dominantly WNT/ß catenin and transforming growth factor-ß (TGF-ß) have been reported to promote differentiation of hMSCs into cardiomyocytes in the prevailing literature, a safe and reproducible system for their clinical application has not yet turned into reality. In the present study, the molecular docking-based strategy was first applied for evaluating the potency of some natural phenolic compounds in the modulation of Wnt and TGF-ß signaling pathways using a vital class of crystallographic protein structures of WNT signaling regulators such as Frizzled, Disheveled, GSK3-ß, ß-catenin, LRP 5/6 extracellular domain, Tankyrase and their variety of active pockets. Then, the impacts of plant-derived chemical compounds on the regulation of the relevant signals for the differentiation of hMSCs into the definitive mesoderm lineage and cardiac progenitors were assessed in vitro. Data obtained revealed the synergistic activity of Wnt and TGF-ß superfamily to direct cardiac differentiation in human cardiogenesis by comparing cardiac gene expression in the presence and absence of the TGF-ß inhibitors. We found that the inhibitory effect of canonical Wnt/ß-catenin is sufficient to cause proper cardiomyocyte differentiation, but the TGF-ß pathway plays a vital role in enhancing the expression of the cardiomyocyte-specific marker (cTnT). It was found that quercetin, a p38MAPK inhibitor with the high energy dock to the active pocket of Wnt receptors, promotes cardiac differentiation via the inhibition of both Wnt and non-Smad TGF-ß pathways. Altogether, data presented here can contribute to the development of a feasible and efficient cardiac differentiation protocol as an "off-the-shelf" therapeutic source using novel natural agents for cardiac repair or regeneration.

19.
Ann Transl Med ; 9(20): 1562, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790768

RESUMO

Background: A disintegrin-like and metalloproteinase domain with thrombospondin type 1 motifs (ADAMTS)-like proteins, including ADAMTSL1-6 and papilin, which are part of the mammalian ADAMTS superfamily, appear to be relevant to extracellular matrix function and the regulation of ADAMTS protease activity. Their roles in tumor initiation and progression and regulating the tumor microenvironment (TME) are now recognized. Methods: In the present study, a comprehensive investigation of the pan-cancer effects of ADAMTSLs and their associations with patient survival, drug responses, and the TME was performed by integrating The Cancer Genome Atlas (TCGA) data and annotated data resources. Results: The expression of ADAMTSL family members was found to be dysregulated in many cancer types. More importantly, their expression was frequently associated with patients' overall survival (OS), drug responses, and the TME. ADAMTSL1, ADAMTSL4, and ADAMTSL5 were primarily associated with aggressive phenotypes, while PAPLN was more frequently associated with a favorable prognosis. In a non-small cell lung cancer (NSCLC) cohort, Thrombospondin Type 1 Domain Containing 4 (THSD4) (ADAMTSL6) and Papilin (PAPLN) were associated with immune checkpoint inhibitor (ICI) sensitivity in samples from the Gene Expression Omnibus repository (GSE135222). Twenty and 30 proteins related to THSD4 and PAPLN, respectively, were identified through a proteomic analysis of 18 Chinese lung adenocarcinoma patients. Conclusions: Our findings extend understandings of the role of the ADAMTSL family in cancers and are a valuable resource on their clinical utility. This article provides insight into the clinical importance of next-generation sequencing technology to identify novel biomarkers for prognosis and investigate therapeutic strategy for clinical benefit.

20.
Front Neurosci ; 15: 755709, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744616

RESUMO

Objective: Intermittent theta burst stimulation (iTBS) is a special form of repetitive transcranial magnetic stimulation (rTMS), which effectively increases cortical excitability and has been widely used as a neural modulation approach in stroke rehabilitation. As effects of iTBS are typically investigated by motor evoked potentials, how iTBS influences functional brain network following stroke remains unclear. Resting-state electroencephalography (EEG) has been suggested to be a sensitive measure for evaluating effects of rTMS on brain functional activity and network. Here, we used resting-state EEG to investigate the effects of iTBS on functional brain network in stroke survivors. Methods: We studied thirty stroke survivors (age: 63.1 ± 12.1 years; chronicity: 4.0 ± 3.8 months; UE FMA: 26.6 ± 19.4/66) with upper limb motor dysfunction. Stroke survivors were randomly divided into two groups receiving either Active or Sham iTBS over the ipsilesional primary motor cortex. Resting-state EEG was recorded at baseline and immediately after iTBS to assess the effects of iTBS on functional brain network. Results: Delta and theta bands interhemispheric functional connectivity were significantly increased after Active iTBS (P = 0.038 and 0.011, respectively), but were not significantly changed after Sham iTBS (P = 0.327 and 0.342, respectively). Delta and beta bands global efficiency were also significantly increased after Active iTBS (P = 0.013 and 0.0003, respectively), but not after Sham iTBS (P = 0.586 and 0.954, respectively). Conclusion: This is the first study that used EEG to investigate the acute neuroplastic changes after iTBS following stroke. Our findings for the first time provide evidence that iTBS modulates brain network functioning in stroke survivors. Acute increase in interhemispheric functional connectivity and global efficiency after iTBS suggest that iTBS has the potential to normalize brain network functioning following stroke, which can be utilized in stroke rehabilitation.

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