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1.
Food Chem ; 368: 130856, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34425333

RESUMO

In this work, we present a novel dual-emissive fluoroimmunoassay for synchronous monitoring of okadaic acid (OA) and saxitoxin (STX) using multicolor fluorescent labels composed of sulfur, phosphorous co-doped graphene quantum dots (S, P-GQDs), and ovalbumin (OVA)-coated gold nanoparticles (OVA-AuNPs). The novel OVA-AuNPs were prepared by the reduction of chloroauric acid under alkaline conditions using OVA as a reducing agent. Both S, P-GQDs and OVA-AuNPs exhibit bright fluorescence, more importantly, a large emission wavelength difference (Δλ = 156 nm) under an excitation of 400 nm and relatively independent fluorescence behavior, which are essential to realizing the dual-signal marks in a directly mixing system. Using a competitive fluorescence-linked immunosorbent assay (cFLISA) format, the dual-emissive cFLISA was successfully utilized to measure OA and STX contents in Alectryonella plicatula (commonly named as fingerprint oyster) and the detection results were in good agreement with the commercial enzyme-linked immunosorbent assay (ELISA) kits.


Assuntos
Grafite , Nanopartículas Metálicas , Pontos Quânticos , Ouro , Imunoensaio , Ácido Okadáico , Saxitoxina , Frutos do Mar/análise
2.
Artigo em Inglês | MEDLINE | ID: mdl-34595550

RESUMO

PURPOSE: The pronator quadratus (PQ) is reflected in the surgical approach to the distal radius. This study explores the functional strength of PQ, 12 months after volar plating without repair of PQ. METHODS: A total of 135 patients were identified from our prospectively collected database. All volunteers had grip strength and pronation power tested in the treated and contralateral forearms at 45, 90 and 135 degrees of elbow flexion using a custom-built torque measuring device and hydraulic hand dynamometer to evaluate forearm pronation. RESULTS: Twenty-seven participants were included in the study. No significant difference was identified in mean peak pronation torque between the volar plated and non-treated forearms. Pronation strength was identified as being independent of angle of elbow flexion. Grip strength was correlated with forearm pronation showing no significant difference between groups. CONCLUSIONS: Our results suggest adequate long-term (15-32 months) functional recovery of the pronator quadratus after volar plating. LEVEL OF EVIDENCE: III.

3.
J Gastrointest Oncol ; 12(4): 1428-1443, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532100

RESUMO

Background: The role of circular RNA (circRNA) in gastric cancer (GC) is attracting increasing attention. CircNOP10 (hsa_circ-0034351) has been reported to be upregulated in human GC tissue. However, the biological role and mechanism of circNOP10 in GC remain unknown. Methods: Circular RNA expression profile of GC was detected based on microarray, and circNOP10 was identified for the subsequent investigation. Clinical samples of GC tissue and patient blood were obtained from the Zhongda Hospital, Southeast University. The different degraded GC cell lines were presented in our laboratory. The function and mechanism of circNOP10 in GC were investigated using Western blot, qRT-PCR, flow cytometry, in situ hybridization and pull down experiment. Results: The results indicated that increased circNOP10 in GC tissue was involved in tumor stage and prognosis. In addition, circNOP10 sponged microRNA-24 (miR-204)-mediated biological processes through sirtuin 1 (SIRT1), which further confirmed that the circNOP10/miR-204/SIRT1 pathway promoted proliferation and migration as well as epithelial-mesenchymal transition (EMT) through the NF-κß pathway in GC cell lines. Conclusions: Candidate oncogene circNOP10 mediated GC cell proliferation, arrest cell cycle in G2/M phase, induced cell apoptosis, enhanced tumor metastasis, as well as EMT by activating the miR-204/SIRT1 pathway, suggesting that it may serve as a potential biomarker in GC therapy.

4.
Langmuir ; 37(37): 11084-11092, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34493039

RESUMO

Giant surfactants with different numbers of aryl-trifluorovinyl ether-functionalized polyhedral oligomeric silsesquioxane (FVPOSS) heads and one poly(ethylene oxide) (PEO) tail, (FVPOSS)n-PEO227, are precisely synthesized. The phase behaviors of (FVPOSS)n-PEO227 at the air-water interface were investigated through surface pressure measurements (isotherm and hysteresis experiments) and the Brewster angle microscopy. Upon increasing the number of FVPOSS heads, the interfacial behaviors of these giant surfactants greatly change. More phase transitions occur during the compression as the number of FVPOSS heads increased from one to two and three. The evolution of morphologies of Langmuir films and compression-expansion hysteresis curves further illustrate phase transitions at the air-water interface. Furthermore, molecular mechanisms to describe phase transitions of (FVPOSS)n-PEO227 at the interface are put forward. This study deepens the understanding of interfacial phase behaviors of special giant surfactants and provides knowledge of nanostructure design and construction at the interface.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34555496

RESUMO

Proximity labeling catalyzed by promiscuous enzymes, such as APEX2, has emerged as a powerful approach to characterize multiprotein complexes and protein-protein interactions. However, current methods depend on the expression of exogenous fusion proteins and cannot be applied to identify proteins surrounding post-translationally modified proteins. To address this limitation, we developed a new method to label proximal proteins of interest by antibody-mediated protein A- ascorbate peroxidase 2 (APEX2) labeling (AMAPEX). In this method, a modified protein is bound in situ by a specific antibody, which then tethers a protein A-APEX2 fusion protein. Activation of APEX2 labels the nearby proteins with biotin; the biotinylated proteins are then purified using streptavidin beads and are identified by mass spectrometry. We demonstrated the utility of this approach by profiling the proximal proteins of histone modifications including H3K27me3, H3K9me3, H3K4me3, H4K5ac, and H4K12ac, as well as verifying the co-localization of these identified proteins with bait proteins by published ChIP-seq analysis and nucleosome immunoprecipitation. Overall, AMAPEX is an efficient tool to identify proteins that are proximal to modified histones.

6.
Front Immunol ; 12: 712936, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489962

RESUMO

The engineered "obligate" anaerobic Salmonella typhimurium strain YB1 shows a prominent ability to repress tumor growth and metastasis, which has great potential as a novel cancer immunotherapy. However, the antitumor mechanism of YB1 remains unelucidated. To resolve the proteome dynamics induced by the engineered bacteria, we applied tumor temporal proteome profiling on murine bladder tumors after intravenous injection of either YB1 or PBS as a negative control. Our data suggests that during the two weeks treatment of YB1 injections, the cured tumors experienced three distinct phases of the immune response. Two days after injection, the innate immune response was activated, particularly the complement and blood coagulation pathways. In the meantime, the phagocytosis was initiated. The professional phagocytes such as macrophages and neutrophils were recruited, especially the infiltration of iNOS+ and CD68+ cells was enhanced. Seven days after injection, substantial amount of T cells was observed at the invasion margin of the tumor. As a result, the tumor shrunk significantly. Overall, the temporal proteome profiling can systematically reveal the YB1 induced immune responses in tumor, showing great promise for elucidating the mechanism of bacteria-mediated cancer immunotherapy.

7.
Cancer Lett ; 524: 42-56, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34582976

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has the highest fatality rate of any solid tumor, with a five-year survival rate of only 10% in the USA. PDAC is characterized by early metastasis. More than 50% of patients present with distant metastases at the time of diagnosis, and the majority of patients will develop metastasis within 4 years after tumor resection. Despite extensive studies, the molecular mechanisms underlying PDAC metastasis remain unclear. The polyoma enhancer activator protein (PEA3) subfamily was reported to play a vital role in the initiation and progression of multiple tumors. Herein, we found that ETS variant 4 (ETV4) was highly expressed in PDAC tissues and associated with poor survival. Univariate and multivariate analyses revealed that ETV4 expression was an independent prognostic factor for patient survival. Further experiments showed that ETV4 overexpression promoted PDAC invasion and metastasis both in vitro and in vivo. For the first time, we demonstrated that, mechanistically, ETV4 increased CXCR5 expression by directly binding to the CXCR5 promoter region. Knockdown of CXCR5 significantly reversed ETV4-mediated PDAC migration and invasion, while CXCR5 overexpression exerted the opposite effects. Intriguingly, we found that CXCL13, a specific ligand of CXCR5, increased ETV4 expression and promoted PDAC invasion and metastasis by activating the ERK1/2 pathway. ETV4 knockdown significantly abrogated the enhanced migratory and invasive abilities induced by the CXCL13/CXCR5 axis. In addition, a CXCR5 neutralizing antibody disrupted the CXCL13/ETV4/CXCR5 positive feedback loop and inhibited cell migration and invasion. Overall, in this study, we demonstrated that ETV4 plays a vital role in PDAC metastasis and defined a novel CXCL13/ETV4/CXCR5 positive feedback loop. Targeting this pathway has implications for potential therapeutic strategies for PDAC treatment.

8.
Ther Adv Chronic Dis ; 12: 20406223211039699, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434540

RESUMO

Objective: This meta-analysis aims to assess the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies on COVID-19. Methods: Relevant literatures about GM-CSF antibody treatment in COVID-19 patients were searched from the PubMed, Cochrane Library, Embase, Google scholar, and Baiduscholar databases from the COVID-19 outbreak in December 2019 until 1 January 2021. The primary outcomes included the death, intensive care unit (ICU) admission risk, ventilation requirement, and secondary infection. Results: A total of 12 eligible literature involving 8979 COVID-19 patients were recruited, and they were divided into experimental group (n = 2673) and control group (n = 6306). Using a random-effect model, it is found that the GM-CSF antibody treatment was associated with a 23% decline of the risk of death [odd's ratio (OR): 0.34, 95% confidence interval (CI): 0.21-0.56, p < 0.0001] and a 20% enhancement of ventilation (OR: 1.47, 95% CI: 1.19, 1.80, p = 0.0002). GM-CSF antibody treatment did not have a significant correlation to secondary infection and increased risk of ICU admission in COVID-19 patients, which may be attributed to the older age and the length of stay. Conclusions: Severe COVID-19 patients can benefit from GM-CSF antibodies.

9.
J Formos Med Assoc ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34446340

RESUMO

Acute kidney injury (AKI) is a common syndrome that has a significant impact on prognosis in various clinical settings. To evaluate whether new evidence supports changing the current definition/classification/staging systems for AKI suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, the Taiwan AKI-TASK Force, composed of 64 experts in various disciplines, systematically reviewed the literature and proposed recommendations about the current nomenclature and diagnostic criteria for AKI. The Taiwan Acute Kidney Injury (TW-AKI) Consensus 2020 was established following the principles of evidence-based medicine to investigate topics covered in AKI guidelines. The Taiwan AKI-TASK Force determined that patients with AKI have a higher risk of developing chronic kidney disease, end-stage renal disease, and death. After a comprehensive review, the TASK Force recommended using novel biomarkers, imaging examinations, renal biopsy, and body fluid assessment in the diagnosis of AKI. Clinical issues with regards to the definitions of baseline serum creatinine (sCr) level and renal recovery, as well as the use of biomarkers to predict renal recovery are also discussed in this consensus. Although the present classification systems using sCr and urine output for the diagnosis of AKI are not perfect, there is not enough evidence to change the current criteria in clinical practice. Future research should investigate and clarify the roles of the aforementioned tools in clinical practice for AKI.

11.
Brief Bioinform ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34368837

RESUMO

The identification of protein-ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here, we propose a novel framework, named AIMEE, integrating AI model and enzymological experiments, to identify inhibitors against 3CL protease of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value <3 µM. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to the domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and was proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and for expanding the boundaries of drug discovery. The code and data are available at https://github.com/SIAT-code/AIMEE.

12.
Langmuir ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34343430

RESUMO

As an effective anionic surfactant for chemical flooding, petroleum sulfonate (PS) is often used in conjunction with alkalis to reduce the adsorption loss of PS onto rock and clay surfaces. However, alkali injection can lead to scaling, aggravate the water-sensitive effect of clays, and accelerate polymer hydrolysis. Here, a temperature-responsive biohydrogel-based carrier (XLK) was designed to protect PS from adsorption onto geological features. XLK, an aqueous mixture containing 0.5% xanthan gum, 0.5% locust bean gum, and 2% KCl, was a gel at room temperature and transformed gradually into a sol above 50 °C (sol/gel transition temperature, Tsol/gel). Below the Tsol/gel, most PS was retained in the gel, preventing the adsorption of PS onto quartz sand. Above the Tsol/gel, PS was released into the surrounding medium. After it had been loaded with PS, the storage modulus (G', Pa) of XLK increased from 102 to 103 and the loss modulus (G″, Pa) increased from 101 to 102. Environmental scanning electron microscopy micrographs showed that PS filled gaps within the cross-linked network structure of XLK. Compared with the aqueous XLK formulation, the addition of hydrolyzed polyacrylamide (HPAM) decreased the melt rate of XLK and the interfacial tension (IFT) of PS. Among the constituents of XLK loaded with PS, KCl had the most obvious effect of lowering the shear modulus of HPAM. Sufficient amounts of KCl were effective in reducing the IFT of PS to ultralow levels (10-3 mN/m).

13.
Front Immunol ; 12: 670178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234776

RESUMO

Objective: This study sought to explore the role of metabolic disturbance in immunoregulation of gingivitis targeting T helper 17 cells (Th17)/regulatory T cell (Treg). Materials and Methods: A total of 20 gingivitis patients and 19 healthy volunteers were recruited. Quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate expression patterns of Forkhead box protein P3 (Foxp3), transforming growth factor-ß (TGF-ß), retinoid-related orphan receptor-gammat (RORγt) and interleukin 17A (IL-17A) in the peripheral blood lymphocytes of subjects across the two groups. Moreover, the enzyme-linked immunosorbent assay (ELISA) technique was used to detect levels of TGF-ß, IL-4, IL-6,TL-10 and L-17A secreted in the plasma as well as the SIgA secreted in saliva. Flow cytometry was used to detect the percentage of CD4+CD25+ Foxp3+Treg cells and the percentage of CD4+IL-17A+ Th17 cells in whole blood of subjects in both groups. Gas chromatography-mass spectrometry (GC-MS) was employed to analyze the plasma metabolites in the gingivitis patient group. Statistical analysis was applied to determine whether the plasma metabolites and related metabolic pathways significantly differed between gingivitis patients and healthy controls. Ingenuity pathway analysis (IPA) was employed to identify the potential relation between the metabolites and the Th17 and Treg related pathway. Results: The percentages of CD4+IL17A+Th17 cells and IL-17 significantly increased in the peripheral blood in the gingivitis group. Moreover, the upregulation of IL-17A mRNA and RORγt mRNA were also found in the gingivitis group. However, the percentage of CD4+CD25+ Foxp3+Treg cells and Foxp3 mRNA in the whole blood did not significantly change. However, TGF-ß mRNA as well as TGF-ß, IL-4, IL-6, IL-10 in the periperial blood and SIgA in the saliva were higher in the gingivitis group. Notably, that the ratio of Th17/Treg cells was significantly increased during peripheral circulation. Furthermore, we identified 18 different metabolites which were differentially expressed in plasma between the gingivitis and healthy control groups. Notably, the levels of cholesterol, glycerol 1-octadecanoate, d-glucose, uric acid, cyclohexaneacetic acid, 3-pyridine, tryptophan, and undecane 2,4-dimethyl were significantly up-regulated. whereas the levels of lactic acid, glycine, linoleic acid, monopalmitic acid, glycerol, palmitic acid, pyruvate, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, 1 5-anhydro d-altrol, and boric acid were down-regulated in the gingivitis group, relative to healthy controls. IPA showed that these metabolites are connected to IL17 signaling, TGF-B signaling, and IL10 signaling, which are related closely to Th17 and Treg pathway. Conclusion: Overall, these results showed that disturbance to glycolysis as well as amino and fatty acid metabolism are associated with Th17/Treg balance in gingivitis. Impaired immunometabolism may influence some periodontally involved systemic diseases, hence it is a promising strategy in targeted development of treatment therapies.

14.
J Affect Disord ; 294: 128-136, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34284318

RESUMO

BACKGROUND: We aimed to explore the risk profiles attributable to psychosocial and behavioural problems during the coronavirus disease 2019 pandemic. To this end, we created a risk-prediction nomogram model. METHODS: A national multicentre study was conducted through an online questionnaire involving 12,186 children (6-11 years old) and adolescents (12-16 years old). Respondents' psychosocial and behavioural functioning were assessed using the Achenbach Child Behaviour Checklist (CBCL). Data were analysed using STATA software and R-language. RESULTS: The positive detection rate of psychological problems within Wuhan was greater than that outside Wuhan for schizoid (P = 0.005), and depression (P = 0.030) in children, and for somatic complaints (P = 0.048), immaturity (P = 0.023), and delinquent behaviour (P = 0.046) in adolescents. After graded multivariable adjustment, seven factors associated with psychological problems in children and adolescents outside Wuhan were parent-child conflict (odds ratio (OR): 4.94, 95% confidence interval (95% CI): 4.27-5.72), sleep problems (OR: 4.05, 95% CI: 3.77-4.36), online study time (OR: 0.41, 95% CI: 0.37-0.47), physical activity time (OR: 0.510, 95% CI: 0.44-0.59), number of close friends (OR: 0.51, 95% CI: 0.44-0.6), time spent playing videogames (OR: 2.26, 95% CI: 1.90-2.69) and eating disorders (OR: 2.71, 95% CI: 2.35-3.11) (all P < 0.001). Contrastingly, within Wuhan, only the first four factors, namely, parent-child conflict (5.95, 2.82-12.57), sleep problems (4.47, 3.06-6.54), online study time (0.37, 0.22-0.64), and physical activity time (0.42, 0.22-0.80) were identified (all P < 0.01). Accordingly, nomogram models were created with significant attributes and had decent prediction performance with C-indexes over 80%. LIMITATION: A cross-sectional study and self-reported measures. CONCLUSIONS: Besides the four significant risk factors within and outside Wuhan, the three additional factors outside Wuhan deserve special attention. The prediction nomogram models constructed in this study have important clinical and public health implications for psychosocial and behavioural assessment.


Assuntos
COVID-19 , Comportamento Problema , Adolescente , Criança , Estudos Transversais , Humanos , Nomogramas , Pandemias , Fatores de Risco , SARS-CoV-2
15.
Chin J Integr Med ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319503

RESUMO

OBJECTIVE: To provide evidence on the efficacy and safety of Chinese herbal medicine (CHM) as interventions for systemic lupus erythematosus (SLE). METHODS: Seven electronic databases, including the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Service System (SinoMed), Wanfang, Embase, and PubMed, were comprehensively searched, from their inception to August 16, 2020, for all randomized controlled trials (RCTs) that focused on CHM used alone or in combination with conventional medicine for SLE. Outcomes were SLE activity index (SLEDAI), traditional Chinese medicine symptom/syndrome score (TCMSS), dosage of glucocorticoids, main serological testing, and incidence of adverse events. Data were extracted and pooled using Review Manager 5.3 software. RESULTS: A total of 13 RCTs enrolling 856 participants met our inclusion criteria. Meta-analyses showed that, compared to placebo, CHM had statistically significant effect on reducing SLEDAI score (MD=-1.74, 95% CI: -2.29 to -1.18), diminishing TCMSS (SMD=-0.89, 95% CI: -1.16 to -0.62), decreasing dosage of glucocorticoids (MD=-2.41 mg/d, 95% CI: -3.34 to -1.48), lowering erythrocyte sedimentation rate (MD=-4.78 mm/h, 95% CI: -8.86 to -0.71), and increasing serum complement C4 level (MD=0.03 mg/dL, 95% CI: 0.00 to 0.06). No significant difference was found between CHM and placebo on adverse events. CONCLUSIONS: CHM provided significant beneficial effect on controlling disease activity and reducing dose of glucocorticoids used among SLE patients. Future advanced designed RCTs for CHM treating moderate to severe SLE with multicenter and longer follow-up are urgently needed.

17.
Transl Psychiatry ; 11(1): 342, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083509

RESUMO

This study aims to explore the psychosocial and behavioral problems of children and adolescents in the early stage of reopening schools. In this national cross-sectional study, a total of 11072 students from China were naturally divided into two groups based on their schooling status: reopened schools (RS) and home schooling (HS) group. The psychosocial and behavioral functioning were measured by Achenbach Child Behaviour Checklist (CBCL) and compared in these two groups. Multivariable logistic regression analyses were conducted to explore the independent predictors associated with the psychosocial and behavioral problems. Our results showed that the students in the RS group had more adverse behaviors than that of HS group. The RS group had the higher rates of parent-offspring conflict, prolonged homework time, increased sedentary time and sleep problems (all p < 0.001). When separate analyses were conducted in boys and girls, the RS group had the higher scores for (1) overall behavioral problems (p = 0.02 and p = 0.01), internalizing (p = 0.02 and p = 0.02) and externalizing (p = 0.02 and p = 0.004) behaviors in the 6-11 age group; (2) externalizing (p = 0.049 and p = 0.006) behaviors in the 12-16 age group. Multivariable regression showed parent-offspring conflict and increased sedentary time were the most common risk factors, while physical activity and number of close friends were protective factors for behavior problems in RS students (p < 0.01 or 0.05). The present study revealed that students' psychosocial and behavioral problems increased in the early stage of schools reopened unexpectedly. These findings suggest that close attention must be paid and holistic strategies employed in the school reopening process of post-COVID-19 period.


Assuntos
COVID-19 , Comportamento Problema , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2 , Instituições Acadêmicas
18.
Biofactors ; 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34153134

RESUMO

Cerebral ischemia-reperfusion injury (CI/RI) is one of the most common diseases of the central nervous system. At present, there is no specific treatment for CI/RI. It is necessary to explore the mechanism of CI/RI and find new ways to prevent and treat CI/RI. An oxygen and glucose deprivation/recovery (OGD/R) model was established to evaluate the effects of mouse astrocytes (MA-C) cell viability and apoptosis of stepwise exposure to oxygen and glucose deprivation followed by their replenishment. This assessment included using taurine upregulated gene 1-small interfering RNAs (TUG1-siRNA) transfection to determine the effects of TUG1 knockdown on MA-C survival and apoptosis. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to evaluate TUG1 and miR-142-3p expression levels. The luciferase gene reporter assay was performed to validate that miR-142-3p is a TUG1 target. Accordingly, the effects of miR-142-3p knockdown on TUG1-induced MA-C apoptosis were determined using flow cytometry. Methyl thiazolyl tetrazolium (MTT) method was used to detect cell growth viability. Western blotting analysis was performed to detect the expression levels of apoptosis-related proteins. TUG1 was upregulated, while miR-142-3p was downregulated in the OGD/R model of MA-C cells. Inhibiting the expression of TUG1 could protect MA-C cells and reverse the decrease in growth viability and increasing apoptosis of MA-C cells caused by OGD/R stimulation. On the other hand, the inhibition of miR-142-3p offset the effect of TUG1 knockdown on cell viability and apoptosis. Inhibition of OGD/R-induced increases in TUG1 expression that in turn reduces miR-142-3p upregulation may suppress reperfusion-induced losses in cell viability.

19.
Foot Ankle Int ; 42(9): 1144-1152, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34041931

RESUMO

BACKGROUND: Despite advancements in operative techniques and the extraordinary number of procedures described for correcting hallux valgus (HV), there is still uncertainty as to why some patients thrive postoperatively whereas others do not. This study aimed to investigate whether the postoperative outcome of HV surgery could be predicted from patient demographics or functional impairment at the time of referral. METHODS: The prospectively collected data, from 92 patients, were analyzed to determine whether patient demographics significantly influenced outcome 52 weeks after surgery. Potential relationships between socioeconomic deprivation and the outcome, as well as between preoperative functional impairment and postoperative improvement, were examined. The Manchester Oxford Foot Questionnaire (MOXFQ) and Scottish Index of Multiple Deprivation (SIMD) were used in this evaluation. RESULTS: None of the demographics studied were found to be statistically significant determinants of outcome. Preoperative MOXFQ scores for patients from the most deprived areas were significantly worse at the time of referral. Patients living in the least deprived postcodes experienced the lowest improvement in MOXFQ scores. Patients from the most deprived SIMD quintile achieved significantly higher improvement in MOXFQ-walking and standing compared to those from the least deprived quintile. A strong positive correlation was found between the preoperative MOXFQ scores and the improvement in the scores postoperatively. CONCLUSION: In this patient cohort, demographics could not be used to predict the postoperative outcome at week 52. Socioeconomic disparities seem to influence the timing of patients seeking surgery. Lower preoperative MOXFQ scores strongly correlate with a lesser degree of postoperative improvement. LEVEL OF EVIDENCE: Level III, retrospective study with prospective arm.

20.
Hum Reprod ; 36(8): 2371-2381, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34037756

RESUMO

STUDY QUESTION: Are any novel mutations and corresponding new phenotypes, other than recurrent hydatidiform moles, seen in patients with MEI1 mutations? SUMMARY ANSWER: We identified several novel mutations in MEI1 causing new phenotypes of early embryonic arrest and recurrent implantation failure. WHAT IS KNOWN ALREADY: It has been reported that biallelic mutations in MEI1, encoding meiotic double-stranded break formation protein 1, cause azoospermia in men and recurrent hydatidiform moles in women. STUDY DESIGN, SIZE, DURATION: We first focused on a pedigree in which two sisters were diagnosed with recurrent hydatidiform moles in December 2018. After genetic analysis, two novel mutations in MEI1 were identified. We then expanded the mutational screening to patients with the phenotype of embryonic arrest, recurrent implantation failure, and recurrent pregnancy loss, and found another three novel MEI1 mutations in seven new patients from six families recruited from December 2018 to May 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine primary infertility patients were recruited from the reproduction centers in local hospitals. Genomic DNA from the affected individuals, their family members, and healthy controls was extracted from peripheral blood. The MEI1 mutations were screened using whole-exome sequencing and were confirmed by the Sanger sequencing. In silico analysis of mutations was performed with Sorting Intolerant From Tolerant (SIFT) and Protein Variation Effect Analyzer (PROVEAN). The influence of the MEI1 mutations was determined by western blotting and minigene analysis in vitro. MAIN RESULTS AND THE ROLE OF CHANCE: In this study, we identified five novel mutations in MEI1 in nine patients from seven independent families. Apart from recurrent hydatidiform moles, biallelic mutations in MEI1 were also associated with early embryonic arrest and recurrent implantation failure. In addition, we demonstrated that protein-truncating and missense mutations reduced the protein level of MEI1, while the splicing mutations caused abnormal alternative splicing of MEI1. LIMITATIONS, REASONS FOR CAUTION: Owing to the lack of in vivo data from the oocytes of the patients, the exact molecular mechanism(s) involved in the phenotypes remains unknown and should be further investigated using knock-out or knock-in mice. WIDER IMPLICATIONS OF THE FINDINGS: Our results not only reveal the important role of MEI1 in human oocyte meiosis and early embryonic development, but also extend the phenotypic and mutational spectrum of MEI1 and provide new diagnostic markers for genetic counseling of clinical patients. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2018YFC1003800, 2017YFC1001500, and 2016YFC1000600), the National Natural Science Foundation of China (81725006, 81822019, 81771581, 81971450, and 81971382), the project supported by the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Project of the Shanghai Municipal Science and Technology Commission (19JC1411001), the Natural Science Foundation of Shanghai (19ZR1444500), the Shuguang Program of the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission (18SG03), the Shanghai Health and Family Planning Commission Foundation (20154Y0162), the Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine, Ferring Pharmaceuticals and the Chinese Academy of Sciences (FIRMC200507) and the Chongqing Key Laboratory of Human Embryo Engineering (2020KFKT008). No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Azoospermia , Animais , Proteínas de Ciclo Celular/genética , China , Feminino , Humanos , Masculino , Camundongos , Mutação , Oócitos , Fenótipo , Gravidez
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