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Thioredoxin peroxidase (TPx) protein from the excretory-secretory antigens (ESAs) of Cysticercus cellulosae (C. cellulosae) has been shown to regulate the differentiation of host Treg and Th17 cells, resulting in an immunosuppressive response dominated by Treg cells. However, the molecular mechanism by which TPx protein from the ESAs of C. cellulosae regulates the imbalance of host Treg/Th17 cell differentiation has not been reported. TPx protein from porcine C. cellulosae ESAs was used to stimulate Jurkat cells activated with PMA and ionomycin at 0, 24, 48, and 72 h. Transcriptomic analysis was performed to investigate the signaling pathways associated with Jurkat cells differentiation regulated by TPx protein from C. cellulosae ESAs. Gene Set Enrichment Analysis (GSEA) revealed that TPx protein from porcine C. cellulosae ESAs could induce upregulation of the TGF-ß signaling pathway and downregulation of Th17 cell differentiation in Jurkat cells. TPx protein from porcine C. cellulosae ESAs can activate the TGF-ß signaling pathway in Jurkat cells, thereby regulating the differentiation of Treg/Th17 cells and leading to an immunosuppressive response dominated by Treg cells, enabling evasion of the host immune attack. This study provides a foundation for further validation of these pathways and further elucidates the molecular mechanisms underlying immune evasion caused by porcine C. cellulosae.
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Cysticercus , Células Th17 , Humanos , Animales , Porcinos , Células Jurkat , Peroxirredoxinas , Diferenciación Celular , Perfilación de la Expresión Génica , Linfocitos T Reguladores , Transducción de Señal , Factor de Crecimiento Transformador betaRESUMEN
BACKGROUND: Few studies have compared the outcomes of regenerative endodontic procedures (REPs) and calcium hydroxide apexification focusing on necrotic teeth with dens evaginatus. AIM: To qualitatively and quantitatively compare the treatment outcomes of REPs and calcium hydroxide apexification in teeth with dens evaginatus. DESIGN: Immature permanent necrotic evaginated teeth treated with REPs or calcium hydroxide apexification for a follow-up period of at least 12 months were included. Tooth success and survival rates were analyzed. Changes in radiographic root length, apical diameter, and radiographic root area (RRA) were quantified. Prognostic factors that might influence RRA were identified via multivariate linear regression analysis. RESULTS: A total of 112 teeth (50 REP cases and 62 apexification cases) with a median follow-up period of 26.5 months were included. Regenerative endodontic procedures and calcium hydroxide apexification exhibited similar satisfactory success and survival rates (p > .05). Additionally, 88 teeth were quantitatively analyzed. The REP group presented a significantly greater percentage increase in RRA and less decrease in apical diameter than the calcium hydroxide apexification group (p < .05). Teeth treated with REPs and with Stages 7 and 8 of root development showed a better gain in RRA (p < .05). CONCLUSION: While REP and calcium hydroxide apexification had similar success and survival rates, teeth with REPs showed an increase in RRA, indicating that REP is the preferred choice.
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Apexificación , Endodoncia Regenerativa , Humanos , Apexificación/métodos , Hidróxido de Calcio/uso terapéutico , Estudios Retrospectivos , Necrosis de la Pulpa Dental/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess whether professional fluoride application (PFA) used in addition to regular fluoride toothpaste (RFT, ≥ 1,000 ppm) is more effective than RFT alone in children. MATERIALS AND METHODS: A systematic search was conducted using the PubMed, Embase, Google Scholar and CENTRAL databases. Randomized controlled trials (RCTs) comparing the effectiveness of RFT + PFA and RFT alone were included. Meta-analyses with random-effects models were performed. The certainty of evidence was assessed using the GRADE approach. RESULTS: A total of 2,729 records were identified from electronic and manual searches, which were screened by two reviewers independently and in duplicate. Six RCTs (5,034 participants) were included, of which four had high risk of bias and two had unclear risk of bias. The PFA used in all these trials was fluoride varnish (FV). In meta-analyses, no significant difference was observed between participants receiving FV + RFT and RFT alone of d(m/e)fs increment (mean difference (MD) - 0.17, 95% confidence interval (CI) - 0.60 to 0.26, P = 0.43, I2 = 38%; 6 trials, 5,034 participants, moderate certainty evidence), incidence of caries (risk ratio (RR) 0.91, 95% CI 0.80 to 1.05, P = 0.21, I2 = 41%; 4 trials, 4,487 participants, moderate certainty evidence) or changes in prevalence of caries (RR 0.89, 95% CI 0.78 to 1.01, P = 0.07, I2 = 0%, 4 trials, 4,189 participants, low certainty evidence). CONCLUSIONS: Low to moderate certainty evidence suggests that FV does not have significant additional caries-preventive benefit for children (under 8 years old) when provided as an adjunct to daily tooth brushing with RFT (≥ 1,000 ppm). There is insufficient evidence regarding the additional benefit of other PFA interventions. CLINICAL RELEVANCE: The decision to apply FV to children needs to be made in light of their actual usage of RFT. TRIAL REGISTRATION: PROSPERO (CRD42020165270).
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Caries Dental , Pastas de Dientes , Niño , Caries Dental/epidemiología , Caries Dental/prevención & control , Fluoruros , HumanosRESUMEN
BACKGROUND: The COVID-19 pandemic posed a great challenge to paediatric dentistry, which confronted with the restriction of service and resource shortage. AIM: To retrospectively analyse the information of children's dental online health consultation during the COVID-19 pandemic in China, and to provide methods to distinguish between dental emergencies and non-emergencies as well as their management. DESIGN: We collected all the online consultation information in Dept. of Paediatric dentistry, School & Hospital of Stomatology, Wuhan University, from 2 February to 31 March 2020, and extracted the information of age, gender, reason for consultation, description of symptom, and preliminary diagnosis of the children. RESULTS: A total of 474 online consultations of paediatric dentistry were included within 59 days during lockdown, and 190 (40.1%) were dental emergencies and 284 (59.9%) non-emergencies. Of 190 emergency consultations, 186 (97.9%) showed swelling, pain, and trauma with or without systemic symptoms. Among 284 non-emergency consultations, retained primary teeth (n = 126) and orthodontic consultation (n = 53) were the most common reasons for consultation. CONCLUSION: The paediatric emergency and non-emergency problems should be clearly distinguished and sufficient instructions provided in the special period of COVID-19. Priorities also should be set to deal with urgent conditions after the release of lockdown.
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COVID-19 , Niño , China/epidemiología , Humanos , Pandemias , Odontología Pediátrica , Derivación y Consulta , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. Significantly activated uridine nucleotide and fatty acid metabolism in HCC cells promote malignant proliferation and immune evasion. Herein, it is demonstrated that the tripartite motif 65 (TRIM65) E3 ubiquitin-protein ligase, O-GlcNAcylated via O-GlcNAcylation transferase, is highly expressed in HCC and facilitated metabolic remodeling to promote the accumulation of products related to uracil metabolism and palmitic acid, driving the progression of HCC. Mechanistically, it is showed that TRIM65 mediates ubiquitylation at the K44 residue of neurofibromatosis type 2 (NF2), the key protein upstream of classical Hippo signaling. Accelerated NF2 degradation inhibits yes-associated protein 1 phosphorylation, inducing aberrant activation of related metabolic enzyme transcription, and orchestrating metabolic and immune advantages. In conclusion, these results reveal a critical role for the TRIM family molecule TRIM65 in supporting HCC cell survival and highlight the therapeutic potential of targeting its E3 ligase activity to alter the regulation of proteasomal degradation.
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For Shenyang, the central city of Northeast China, its municipal-level Territorial Spatial Planning is of great significance to the whole of Northeast China. Territorial Spatial Planning is an essential carrier of China's ecological civilization construction. The demarcation of "three districts and three lines" defines the scope of ecological protection areas, which is of guiding significance to the future development of ecological civilization construction. The regional ecological vulnerability assessment can provide reference for ecological pattern planning and the demarcation of ecological red lines in "three districts and three lines". In order to explore the spatial distribution pattern of ecological vulnerability in Shenyang, predict the development trend of ecological vulnerability in the future and guide the construction of ecological civilization in Shenyang and provide certain basis for Shenyang's Territorial Spatial Planning and the delineation of "three districts and three lines". This paper based on the "sensitivity-resilience-pressure" model selected 13 indexes, to evaluate the ecological vulnerability of Shenyang from 2010 to 2020. Furthermore, the spatial distribution characteristics and influencing factors of ecological vulnerability in Shenyang are summarized using spatial autocorrelation analysis and geographic detector model, and the future development trend of ecological vulnerability in Shenyang in 2025 is predicted by using CA-Markov model. The results show that: (1) In 2010, 2015 and 2020, the total area of slightly vulnerable areas in Shenyang was large, and the ecological vulnerability showed a gradually vulnerable spatial change trend from south to north and from west to east. (2) The results of geographical detectors show that normalized difference vegetation index, economic density and nighttime light intensity are the main driving factors of ecological vulnerability in Shenyang. (3) The forecast result of CA-Markov model is reliable. In 2025, the ecological vulnerability of Shenyang will be mainly light and extreme vulnerability areas, and the areas of light and extreme vulnerability areas will increase in 2025. The research results can provide some reference for the delineation of "three districts and three lines" and ecological protection in Shenyang's Territorial Spatial Planning, and have certain significance for promoting regional sustainable development and balancing ecological protection and economic development.
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Conservación de los Recursos Naturales , Ecosistema , Conservación de los Recursos Naturales/métodos , China , Ciudades , Desarrollo SostenibleRESUMEN
BACKGROUND: Ischemic stroke (IS) is the most common cardiovascular and cerebrovascular disease in clinic. Qiangli Tianma Duzhong Capsule (TMDZ capsule) has significant therapeutic effect to IS. Therefore, it is great significance to explore the mechanism of action of TMDZ capsules in the treatment of IS. METHODS: The potential active components and possible targets of TMDZ capsule were obtained from TCMSP and The Encyclopedia of Traditional Chinese Medicine databases. IS related targets were collected by Genecard database, OMIM database, TTD database and DisGeNET database. The common target network of drug-diseases was constructed using Cytoscape for visualization analysis. Potential mechanisms were identified through enrichment analysis of gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Three key targets (ALB, TNF, and INS) were selected from the key networks with high correlation scores in PPI for molecular docking, through molecular docking, the interaction between target and protein is visualized. RESULTS: 59 active components and 648 targets of TMDZ capsules and 2286 targets of IS were obtained through database mining. Compound-target network is constructed with 117 nodes and 1185 edges. GO and KEGG suggest that lipids and atherosclerosis, fluid shear forces and atherosclerosis, neurodegenerative pathways - multiple diseases and blood circulation play important roles in the treatment of IS. CONCLUSIONS: This study reveals the molecular mechanism of TMDZ capsules in the treatment of IS by integrating molecular docking with a network pharmacological strategy, which not only confirmed the clinical efficacy of TMDZ capsule, but also laid the foundation for further experimental research.
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Aterosclerosis , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Humanos , Simulación del Acoplamiento Molecular , Cápsulas , Farmacología en Red , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
BACKGROUND: Naoshuantong capsule (NST capsule) is a classic Chinese patent medicine, which can treat ischemic stroke (IS) and has good clinical efficacy. However, its pharmacological mechanism remains to be further explored in the treatment of IS. METHODS: The bio-active components and potential targets of NST Capsules were obtained by ETCM and TCMSP databases. In addition, the related targets of IS were collected by Genecard, OMIM, DrugBank, TTD and DisGeNET databases. NST-IS common target was obtained by Venn platform. PPI network of NST-IS common target and the composition - target network diagram of NST Capsule were constructed by Cytoscape3.8.1. Finally, AutoDock was used for molecular docking. RESULTS: 265 targets were predicted from 32 active compounds in NST Capsule, 109 common targets were identified between NST Capsule and IS. The top 10 key targets of PPI network were ALB, TNF, TP53, VEGFA, CASP3, MYC, etc. Enrichment analysis showed that NST capsules treated IS mainly through lipid and atherosclerosis, fluid shear stress and atherosclerosis signaling pathways. CONCLUSION: Through the methods of network pharmacology and molecular docking, this study clarified that NST capsules play a role in the treatment of IS, which is multi-target, multi-channel and multi-component regulation. This study further explored the pharmacological mechanism of NST capsule in the treatment of IS, which can provide some references for the subsequent research in the pharmacological mechanism of NST capsule.
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Aterosclerosis , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Humanos , Farmacología en Red , Simulación del Acoplamiento Molecular , Pueblo AsiaticoRESUMEN
Water-soluble AgInS2 (AIS) quantum dots (QDs) were successfully prepared through the one-pot water phase method with thioglycolic acid (TGA) as the stabilizing agent. Because enrofloxacin (ENR) effectively quenches the fluorescence of AIS QDs, a highly-sensitive fluorescence detection method is proposed to detect ENR residues in milk. Under optimal detection conditions, there was a good linear relationship between the relative fluorescence quenching amount (ΔF/F0) of AgInS2 with ENR and ENR concentration (C). The detection range was 0.3125-20.00 µg/mL, r = 0.9964, and the detection limit (LOD) was 0.024 µg/mL (n = 11). The average recovery of ENR in milk ranged from 95.43 to 114.28%. The method established in this study has advantages including a high sensitivity, a low detection limit, simple operation and a low cost. The fluorescence quenching mechanism of AIS QDs with ENR was discussed and the dynamic quenching mechanism of light-induced electron transfer was proposed.
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Puntos Cuánticos , Animales , Enrofloxacina/análisis , Colorantes Fluorescentes/química , Agua/química , Leche/químicaRESUMEN
The study aims to investigate and compare the success rate of concentrated growth factor (CGF) and blood clot (BC) as scaffolds in regenerative endodontic procedures (REPs). Immature permanent necrotic teeth treated by REPs with at least a 6-month follow-up were included. These teeth were divided into the CGF (53 teeth) and BC (68 teeth) groups. Treatment outcomes were assessed using a combined clinical and radiographic scoring system. The total success rate was 91.74% over a mean follow-up period of 23.15 months. There was no significant difference between the CGF group (86.79%) and BC group (95.59%). The success rate of traumatic teeth (84.31%) was significantly lower than that of teeth with developmental dental anomalies (98.39%) (p < 0.05). CGF may be a suitable alternative scaffold in REPs when adequate bleeding cannot be achieved. Moreover, compared to developmental dental anomalies, traumatic teeth treated by REPs may be more vulnerable to failure.
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Endodoncia Regenerativa , Trombosis , Humanos , Necrosis de la Pulpa Dental/terapia , Estudios Retrospectivos , Péptidos y Proteínas de Señalización IntercelularRESUMEN
Excretory-secretory antigens (ESAs) of Cysticercus cellulosae can directly regulate the proliferation and differentiation of host T regulatory (Treg) cells, thus inhibiting host immune responses. However, previous studies have only focused on this phenomenon, and the molecular mechanisms behind the ways in which C. cellulosae ESAs regulate the differentiation of host Treg/Th17 cells have not been reported. We collected CD3+ T cells stimulated by C. cellulosae ESAs through magnetic bead sorting and used label-free quantification (LFQ) proteomics techniques to analyze the signaling pathways of C. cellulosae ESAs regulating Treg/Th17 cell differentiation. Through gene set enrichment analysis (GSEA), we found that C. cellulosae ESAs could upregulate the TGF-ß signaling pathway and downregulate Th17 cell differentiation in piglet T cells. Interestingly, we also found that the IL-2/STAT5 signaling pathway also affects the downregulation of Th17 cell differentiation. C. cellulosae ESAs activate the TGF-ß signaling pathway and the IL-2/STAT5 signaling pathway in host T cells to further regulate the differentiation of Treg/Th17 cells in order to evade host immune attack. This study lays the foundation for the subsequent verification of these pathways, and further clarifies the molecular mechanism of C. cellulosae-mediated immune evasion.
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Objective: The aim of this study was to investigate the characteristics of intestinal flora in patients with functional gastroenteropathy and generalized anxiety disorder (GAD) and the relationship between intestinal flora and psychological factors. Materials and methods: From March 2020 to December 2020, a total of 35 patients with functional gastroenteropathy and generalized anxiety disorder, 30 healthy controls, 16 patients with functional gastroenteropathy, and 44 patients with generalized anxiety disorder were selected from the Affiliated Hospital of Guizhou Medical University. Fecal samples were collected from each group, and the related psychophysiological factors scales (Hamilton Anxiety Scale, Hamilton Depression Scale, Neurotic Personality Questionnaire, concept of illness questionnaire, Toronto Alexithymia Scale, Severity of Physical Symptoms Scale, and Cognitive Emotion Regulation Questionnaire) were improved. 16S rRNA high-pass sequencing was used to determine the correlation between intestinal flora changes and functional gastroenteropathy with generalized anxiety disorder. Then, the scale and gut microbiota results were analyzed for correlation to determine the correlation between personality traits and gut microbiota. Results: We found similar intestinal microbiota in patients with functional gastroenterology, generalized anxiety disorder, and functional gastroenteropathy with generalized anxiety disorder. But the relative abundance of Clostridium was significantly increased in patients with functional gastrointestinal disease (FGID) and generalized anxiety. The relative abundance of Haemophilus influenzae was significantly increased in patients with functional gastrointestinal disease without a generalized anxiety disorder. The intestinal microecological composition was significantly correlated with personality traits. Conclusion: Functional gastrointestinal disease comorbidity GAD may be related to an increase in the relative abundance of Fusobacterium. FGID non-comorbidity GAD may be related to the increased relative abundance of Hemophilus. The increased relative abundance of Fusobacterium and Megamonas is associated with personality traits such as difficulty describing feelings and difficulty identifying feelings, neuroticism, and negative cognition of disease.
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INTRODUCTION: This retrospective study aimed to evaluate the clinical and radiographic outcomes of regenerative endodontic procedures (REPs) for traumatic immature permanent teeth. Meanwhile, predictors influencing treatment outcomes were also analyzed to provide evidence for the management of immature teeth after different traumatic scenarios. METHODS: Traumatized immature permanent teeth diagnosed with pulp necrosis treated by REPs using blood clot or concentrated growth factor scaffolds with at least 6 months of follow-up were included from 2012 to 2021. Treatment outcomes were categorized as a success or failure and survival. Further root development was assessed in terms of the percentage changes in the apical diameter, root length, and radiographic root area. Among different injury types, the clinical and radiographic outcomes of REPs were evaluated by the Fisher exact test and the Kruskal-Wallis test, respectively. Survival analysis and Cox regression analysis were performed to identify significant predictors affecting outcomes. RESULTS: Sixty-two teeth with a mean of 22.3 months of follow-up satisfied the criteria, and 80.6% of the teeth had a successful outcome. A significant change was observed in a decrease of the apical diameter (69.3%) and an increase of the radiographic root area (22.6%) after REPs. Among different injury types, the success rates of REPs were as follows: fracture, 84.6%; luxation, 83.3%; combined injuries, 78.6%; and avulsion, 33.3% (P > .05). Fractured teeth had a significantly greater decrease of the apical diameter than combined injuries (P < .05). Avulsion was more prone to developing root resorption than fracture (P < .05). Scaffold was a significant predictor for success; a blood clot had a significantly reduced risk for failure than concentrated growth factor (hazard ratio = 16; 95% confidence interval, 2.1-125.2; P < .001). CONCLUSIONS: REPs provided satisfactory outcomes in traumatized immature permanent necrotic teeth. However, severe injuries, especially avulsion, should be determined carefully to perform REPs when resorption is expected. Scaffold selection may be an important consideration.
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Endodoncia Regenerativa , Trombosis , Necrosis de la Pulpa Dental/terapia , Humanos , Necrosis , Estudios Retrospectivos , Tratamiento del Conducto Radicular/métodos , Resultado del TratamientoRESUMEN
Taenia solium (T. solium) cysticercosis is a neglected parasitic zoonosis that occurs in developing countries. Since T. solium has a complex life cycle that includes eggs, oncospheres, cysticerci, and adults, presumably many proteins are produced that enable them to survive and establish an infection within the host. The objectives of this study were to perform a comparative proteomic analysis of two ontogenetic stages of T. solium (cysticerci and adult) and to analyze their differential expression of proteins. Methods proteins were separated by High Performance Liquid Chromatography (HPLC) fractionation, and protein samples were also digested in liquid and identified by liquid chromatography tandem mass spectrometry (LC-MS/MS); the differentially expressed proteins were then processed by a bioinformatics analysis and verified by parallel reaction monitoring (PRM). Results we identified 2,481 proteins by label-free quantitative proteomics. Then differentially expressed proteins were screened under P values < 0.05 and 2 fold change, we found that 293 proteins up-regulated and 265 proteins down-regulated. Discussion through the bioinformatics analysis, we analyzed the differences types and functions of proteins in the Taenia solium and cysticercus, the data will provide reference value for studying the pathogenic mechanism of the two stages and the interaction with the host, and also support for further experimental verification.
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Macrophages are highly heterogeneous immune cells that fulfill tissue-specific functions. Tissue-derived signals play a critical role in determining macrophage heterogeneity. However, these signals remain largely unknown. The BMP receptor activin receptor-like kinase 1 (ALK1) is well known for its role in blood vessel formation; however, its role within the immune system has never been revealed to our knowledge. Here, we found that BMP9/BMP10/ALK1 signaling controlled the identity and self-renewal of Kupffer cells (KCs) through a Smad4-dependent pathway. In contrast, ALK1 was dispensable for the maintenance of macrophages located in the lung, kidney, spleen, and brain. Following ALK1 deletion, KCs were lost over time and were replaced by monocyte-derived macrophages. These hepatic macrophages showed significantly reduced expression of the complement receptor VSIG4 and alterations in immune zonation and morphology, which is important for the tissue-specialized function of KCs. Furthermore, we found that this signaling pathway was important for KC-mediated Listeria monocytogenes capture, as the loss of ALK1 and Smad4 led to a failure of bacterial capture and overwhelming disseminated infections. Thus, ALK1 signaling instructs a tissue-specific phenotype that allows KCs to protect the host from systemic bacterial dissemination.
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Receptores de Activinas Tipo II/metabolismo , Macrófagos del Hígado/enzimología , Listeria monocytogenes/metabolismo , Listeriosis/enzimología , Listeriosis/prevención & control , Transducción de Señal , Receptores de Activinas Tipo II/genética , Animales , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Factor 2 de Diferenciación de Crecimiento/genética , Factor 2 de Diferenciación de Crecimiento/metabolismo , Listeriosis/genética , Ratones , Ratones NoqueadosRESUMEN
There is a lack of vaccine against human cysticercosis, thus making a huge population at the risk of infection. In this study, we chose a novel potential antigen molecule Taenia solium 14-3-3.3 (Ts14-3-3.3) and optimized it as sp-Ts14-3-3.3 (sp is immunoglobulin H chain V-region precursor, partial) in order to construct recombinant plasmids pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3. BALB/c mice were divided into four groups for immunization: pMZ-X3-Ts14-3-3.3, pMZ-X3-sp-Ts14-3-3.3, pMZ-X3 plasmid control group and PBS control group. Compared with two control groups, the proliferation level of splenic lymphocytes increased significantly in pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3 groups and reached the maximum in week 6. And the same case arose as cytokines associated with Th1 response, IFN-γ, and IL-2 while those with Th2 response, IL-4, IL-10 went up and reached the maximum in week 4. The levels of serum specific IgG, IgG1 and IgG2a rose and reached the maximum in week 6, 4 and 6, respectively. Meanwhile, the proportion of CD4+/CD8+ splenic T lymphocytes increased and reached the peak in week 6. The results indicated that the recombinant plasmids pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3 can induce specific cellular and humoral immune responses in BALB/c mice with immunization. Notably, the recombinant plasmid pMZ-X3-sp-Ts14-3-3.3 has a better immune effect, which proves that Ts14-3-3.3 enjoys a higher possibility as a potential antigen molecule to T. solium vaccine.
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Taenia solium , Vacunas , Animales , Anticuerpos Antihelmínticos , Inmunidad , Inmunoglobulina G , Ratones , Ratones Endogámicos BALB C , Plásmidos/genética , Taenia solium/genéticaRESUMEN
Obesity is an important risk factor for cardiovascular disease, diabetes and certain cancers. The fat mass- and obesity-associated (FTO) gene is tightly associated with the pathophysiology of obesity, whereas the exact role of FTO remains poorly understood. Here, we investigated the alternations of FTO mRNA and protein expression in the peripheral metabolic tissues and the brain upon energy restriction (ER) and explored the involvement of the leptin signaling pathway in FTO regulation under ER status. ER decreased the FTO mRNA and protein expression in hypothalamus and brainstem but not in periphery. Using double-immunofluorescence staining, FTO was found to be colocalized with the leptin receptor long isoform (LepRb) in arcuate nucleus of hypothalamus and the nucleus of the solitary tract. In LepRb mutant db/db mice, the FTO downregulation in brain and body weight reduction induced by ER were completely abolished. The enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by ER was also impaired in db/db mice. Moreover, leptin directly activated the STAT3 signaling pathway and downregulated FTO in in vitro arcuate nucleus of hypothalamus cultures and in vivo wild-type mice but not db/db mice. Thus, our results provide the first evidence that the LepRb-STAT3 signaling pathway is involved in the brain FTO downregulation during ER.
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Encéfalo/metabolismo , Isoformas de Proteínas/metabolismo , Proteínas/metabolismo , Receptores de Leptina/metabolismo , Factor de Transcripción STAT3/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Animales , Western Blotting , Peso Corporal/genética , Técnica del Anticuerpo Fluorescente , Masculino , Ratones , Isoformas de Proteínas/genética , Proteínas/genética , Ratas , Receptores de Leptina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/genética , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Objective: Stand-to-sit task is an important daily function, but there is a lack of research evidence on whether knee osteoarthritis (knee OA) affects the postural balance during the task. This study aimed to compare individuals with knee OA and asymptomatic controls in postural balance and identify kinematic and lower extremity muscle activity characteristics in individuals with knee OA during the stand-to-sit task. Methods: In total, 30 individuals with knee OA and 30 age-matched asymptomatic controls performed the 30-s Chair Stand Test (30sCST) at self-selected speeds. Motion analysis data and surface electromyography (sEMG) were collected while participants performed the 30sCST. To quantify postural balance, the displacement of the center of mass (CoM) and the peak instantaneous velocity of the CoM were calculated. The kinematic data included forward lean angles of the trunk and pelvic, range of motion (RoM) of the hip, knee, and ankle joints in the sagittal plane. The averaged activation levels of gluteus maximus, vastus lateralis, vastus medialis, rectus femoris, biceps femoris (BF), tibialis anterior (TA), and medial head of gastrocnemius muscles were indicated by the normalized root mean square amplitudes. Results: Compared with the asymptomatic control group, the knee OA group prolonged the duration of the stand-to-sit task, demonstrated significantly larger CoM displacement and peak instantaneous CoM velocity in the anterior-posterior direction, reduced ankle dorsiflexion RoM, greater anterior pelvic tilt RoM, and lower quadriceps femoris and muscles activation level coupled with higher BF muscle activation level during the stand-to-sit task. Conclusion: This study indicates that individuals with knee OA adopt greater pelvic forward lean RoM and higher BF muscle activation level during the stand-to-sit task. However, these individuals exist greater CoM excursion in the anterior-posterior direction and take more time to complete the task. This daily functional activity should be added to the rehabilitation goals for individuals with knee OA. The knee OA group performs reduced ankle dorsiflexion RoM, quadriceps femoris, and TA activation deficit. In the future, the rehabilitation programs targeting these impairments could be beneficial for restoring the functional transfer in individuals with knee OA.
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Cysticercus cellulosae (C. cellulosae) excretes and secretes antigens during the parasitic process to regulate the host immune response; however, resulting immune response and cytokine production in the host during infection still remains unclear. We used C. cellulosae crude antigens (CAs) as controls to explore the effect of excretory secretory antigens (ESAs) on T-cell immune responses in piglets. C. cellulosae ESAs induced imbalanced CD4+/CD8+ T-cell proportions, increased the CD4+Foxp3+ and CD8+Foxp3+ T-cell frequencies, and induced lymphocytes to produce interleukin-10, which was mainly attributed to CD4+ and CD4-CD8- T cells. The ESAs also induced Th2-type immune responses. The results showed that the ability of C. cellulosae to escape the host immune attacks and establish a persistent infection may be related to host immune response regulation by the ESAs.
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Cysticercus , Linfocitos T , Animales , Antígenos , PorcinosRESUMEN
OBJECTIVES: To investigate the impact of total variation regularized expectation maximization (TVREM) reconstruction on the image quality of 68Ga-PSMA-11 PET/CT using phantom and patient data. METHODS: Images of a phantom with small hot sphere inserts and 20 prostate cancer patients were acquired with a digital PET/CT using list-mode and reconstructed with ordered subset expectation maximization (OSEM) and TVREM with seven penalisation factors between 0.01 and 0.42 for 2 and 3 minutes-per-bed (m/b) acquisition. The contrast recovery (CR) and background variability (BV) of the phantom, image noise of the liver, and SUVmax of the lesions were measured. Qualitative image quality was scored by two radiologists using a 5-point scale (1-poor, 5-excellent). RESULTS: The performance of CR, BV, and image noise, and the gain of SUVmax was higher for TVREM 2 m/b groups with the penalization of 0.07 to 0.28 compared to OSEM 3 m/b group (all p < 0.05). The image noise of OSEM 3 m/b group was equivalent to TVREM 2 and 3 m/b groups with a penalization of 0.14 and 0.07, while lesions' SUVmax increased 15 and 20%. The highest qualitative score was attained at the penalization of 0.21 (3.30 ± 0.66) for TVREM 2 m/b groups and the penalization 0.14 (3.80 ± 0.41) for 3 m/b group that equal to or greater than OSEM 3 m/b group (2.90 ± 0.45, p = 0.2 and p < 0.001). CONCLUSIONS: TVREM improves lesion contrast and reduces image noise, which allows shorter acquisition with preserved image quality for PSMA PET/CT. ADVANCES IN KNOWLEDGE: TVREM reconstruction with optimized penalization factors can generate higher quality PSMA-PET images for prostate cancer diagnosis.