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1.
Environ Res ; : 112161, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626591

RESUMO

BACKGROUND: Congenital anomalies (CAs) are the leading causes for children's disabilities and mortalities worldwide. The associations between air pollution and CAs are not fully characterized in fetuses born by in vitro fertilization (IVF) who are at high risk of congenital anomalies. METHODS: We conducted a cross-sectional study including 16,971 IVF cycles from three hospitals in Hebei Province, China, 2014-2019. Air quality data was obtained from 149 air monitoring stations. Individual average daily concentrations of PM2.5, PM10, NO2, SO2, CO, and O3 were estimated by spatiotemporal kriging method. Exposure windows were divided into 5: preantral follicle period, antral follicle period, germinal period, embryonic period and early fetal period. Logistic generalized estimating equations were used to estimate the associations between air pollutants and overall or organ-system specific congenital anomalies. Negative control exposure method was used to detect and reduce bias of estimation. RESULTS: We found increasing levels of PM2.5 and PM10 were associated with higher risk of overall congenital anomalies during early fetal period, equating gestation 10-12 weeks (OR: 1.05, 95% CI: 1.02-1.09, p = 0.013 for a 10 µg/m3 increase of PM2.5; OR: 1.03, 95% CI: 1.01-1.06, p = 0.021 for a 10 µg/m3 increase of PM10). Cleft lip and cleft palate were associated with PM10 in germinal period and early fetal period. The CAs of eye, ear, face and neck were related to CO in preantral follicle stage. We did not find the association between chromosome abnormalities and air pollution exposure. CONCLUSIONS: We concluded that ambient air pollution was a risk factor for congenital anomalies of fetus conceived by IVF, especially exposure in early fetal period.

2.
J Am Chem Soc ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637302

RESUMO

Five libraries of natural and synthetic phenolic acids containing five AB3, ten constitutional isomeric AB2, one AB4, and one AB5 were previously synthesized and reported by our laboratory in 5 to 11 steps. They were employed to construct seven libraries of self-assembling dendrons, by divergent generational, deconstruction, and combined approaches, enabling the discovery of a diversity of supramolecular assemblies including Frank-Kasper phases, soft quasicrystals, and complex helical organizations, some undergoing deracemization in the crystal state. However, higher substitution patterns within a single dendron were not accessible. Here we report three libraries consisting of 30 symmetric and nonsymmetric constitutional isomeric phenolic acids with unprecedented sequenced patterns, including two AB2, three AB3, eight AB4, five AB5, six AB6, three AB7, two AB8, and one AB9 synthesized by accelerated modular-orthogonal Ni-catalyzed borylation and cross-coupling. A single etherification step with 4-(n-dodecyloxy)benzyl chloride transformed all these phenolic acids, of interest also for other applications, into self-assembling dendrons. Despite this synthetic simplicity, they led to a diversity of unprecedented self-organizing principles: lamellar structures of interest for biological membrane mimics, helical columnar assemblies from rigid-solid angle dendrons forming Tobacco Mosaic Virus-like assemblies, columnar organizations from adaptable-solid angle dendrons forming disordered micellar-like nonhelical columns, columns from supramolecular spheres, five body-centered cubic phases displaying supramolecular orientational memory, rarely encountered in previous libraries forming predominantly Frank-Kasper phases, and two Frank-Kasper phases. Lessons from these self-organizing principles, discovered within a single generation of self-assembling dendrons, may help elaborate design principles for complex helical and nonhelical organizations of synthetic and biological matter.

3.
Int J Rheum Dis ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633142

RESUMO

AIM: To review the clinical features of systemic lupus erythematosus (SLE) complicated by central nervous system (CNS) infection due to Listeria monocytogenes. METHOD: A patient with SLE receiving high-dose glucocorticoids combined with cyclophosphamide who developed multiple brain abscesses due to Listeria infection is described. The case is compared with known cases in a literature review. RESULTS: A review of the literature showed that CNS infections are rare bacterial complications of SLE, but they can be a significant cause of mortality, especially those due to L. monocytogenes. The most significant risk factor for listerial meningitis is a prior history of receiving immunosuppressive therapy. At-risk patients should avoid unpasteurized milk and soft cheeses along with deli-style, ready-to-eat prepared meats, particularly poultry products. The case we report is the fifth SLE patient with multiple brain abscesses due to L. monocytogenes, and the first to be discharged with no sequelae. Timely and accurate identification and treatment of CNS infections and neuropsychiatric lupus are very important for favorable disease prognosis. CONCLUSION: Repeated blood culture is helpful for early diagnosis, and empirical anti-infective treatment that covers L. monocytogenes is recommended for SLE patients with risk factors when CNS infection occurs. A comprehensive assessment might be helpful to distinguish CNS infections from neuropsychiatric SLE. For severe infection, the dosage of steroids does not need to be reduced immediately but can be gradually adjusted based on the results of a comprehensive evaluation of the disease.

4.
Cell Death Differ ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635817

RESUMO

Many integral membrane proteins might act as indispensable coordinators in specific functional microdomains to maintain the normal operation of known receptors, such as Notch. Gm364 is a multi-pass transmembrane protein that has been screened as a potential female fertility factor. However, there have been no reports to date about its function in female fertility. Here, we found that global knockout of Gm364 decreased the numbers of primordial follicles and growing follicles, impaired oocyte quality as indicated by increased ROS and γ-H2AX, decreased mitochondrial membrane potential, decreased oocyte maturation, and increased aneuploidy. Mechanistically, Gm364 directly binds and anchors MIB2, a ubiquitin ligase, on the membrane. Subsequently, membrane MIB2 ubiquitinates and activates DLL3. Next, the activated DLL3 binds and activates Notch2, which is subsequently cleaved within the cytoplasm to produce NICD2, the intracellular active domain of Notch2. Finally, NICD2 can directly activate AKT within the cytoplasm to regulate oocyte meiosis and quality.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34606459

RESUMO

Production of functional forces by human motor systems require coordination across multiple muscles. Grip and pinch are two prototypes for grasping force production. Each grasp plays a role in a range of hand functions and can provide an excellent paradigm for studying fine motor control. Despite previous investigations that have characterized muscle synergies during general force production, it is still unclear how intermuscular coordination differs between grip and pinch and across different force outputs. Traditional muscle synergy analyses, such as non-negative matrix factorization or principal component analysis, utilize dimensional reduction without consideration of nonlinear characteristics of muscle co-activations. In this study, we investigated the novel method of multiplex recurrence networks (MRN) to assess the inter-muscular coordination for both grip and pinch at different force levels. Unlike traditional methods, the MRN can leverage intrinsic similarities in muscle contraction dynamics and project its layers to the corresponding weighted network (WN) to better model muscle interactions. Twenty-four healthy volunteers were instructed to grip and pinch an apparatus with force production at 30%, 50%, and 70% of their respective maximal voluntary contraction (MVC). The surface electromyography (sEMG) signals were recorded from eight muscles, including intrinsic and extrinsic muscles spanning the hand and forearm. The sEMG signals were then analyzed using MRNs and WNs. Interlayer mutual information ( I ) and average edge overlap ( ω ) of MRNs and average shortest path length ( L ) of WNs were computed and compared across groups for grasp types (grip vs. pinch) and force levels (30%, 50% and 70% MVC). Results showed that the extrinsic, rather than the intrinsic muscles, had significant differences in network parameters between both grasp types ( ), and force levels ( ), and especially at higher force levels. Furthermore, I and ω were strengthened over time ( ) except with pinch at 30% MVC. Results suggest that the central nervous system (CNS) actively increases cortical oscillations over time in response to increasing force levels and changes in force production with different sustained grasping types. Muscle coupling in extrinsic muscles was higher than in intrinsic muscles for both grip and pinch. The MRNs may be a valuable tool to provide greater insights into inter-muscular coordination patterns of clinical populations, assess neuromuscular function, or stabilize force control in prosthetic hands.

6.
CNS Neurosci Ther ; 27(11): 1425-1428, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633764

RESUMO

In the present study, we performed an exome-wide investigation of the burden of rare disease-causing variants for major depressive disorder (MDD) using 16,702 samples from UK biobank. Gene-based association analysis and candidate gene prioritization analysis indicated that FOXH1 have significant association with MDD. In addition, sphingolipid metabolism pathway was found to be less enriched with rare disease-causing variants in the MDD group, suggesting that this gene set may be involved in the pathophysiology of MDD.

7.
Trials ; 22(1): 693, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635144

RESUMO

BACKGROUND: Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and can lead to heart failure (HF), stroke, pulmonary embolism (PE), and other complications, seriously affecting people's quality of life and health. Western medicine is limited in the treatment of AF, while Traditional Chinese Medicine (TCM) has unique advantages, such as less side effects, low toxicity, long effect duration, and high compliance. The prescription of HTDJ is a common prescription for the treatment of atrial fibrillation in Longhua Hospital, Shanghai University of Traditional Chinese Medicine. It has been used for many years and has a large number of clinically effective cases. It has a good clinical application prospect, but there is a lack of effective evaluation of its clinical efficacy. METHOD: This study adopts a randomized double-blind, single-simulated, placebo-controlled research method. Participants were randomly assigned in a 1:1 ratio through a centrally controlled, computer-generated, simple randomization schedule. Participants would take the medicine for 1 month, and the curative effect would be evaluated. Subsequently, the participants would not take TCM and only receive western medicine treatment. They would be followed up for another 8 weeks, and a clinical evaluation would be conducted. The secondary outcomes include echocardiography, Hamilton Anxiety Scale, Hamilton Depression Scale, rate of increase and decrease of anti-arrhythmia western medicine, the MOS 36-item short-form health survey, N-terminal-pro hormone B-type natriuretic peptide level, and integral TCM syndrome score. Adverse events will be monitored throughout the trial. Cases are from outpatient and inpatient with atrial fibrillation in the Cardiology Department of Longhua Hospital. Evaluations will be conducted at baseline and at weeks 4 and 12 after randomization. DISCUSSION: In this study, the efficacy and safety of HTDJ plus western medicine in the treatment of atrial fibrillation (qi deficiency and phlegm opacities) will be evaluated, so as to provide medical evidence of short-term and medium-term clinical efficacy for the treatment of atrial fibrillation with integrated traditional and western medicine and lay a foundation for further clinical development and application. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000030517 . Registered on March 5, 2020, with the Chinese Clinical Trial Registry.


Assuntos
Fibrilação Atrial , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , China , Método Duplo-Cego , Humanos , Medicina Tradicional Chinesa , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Microbiol Res ; 253: 126883, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34626929

RESUMO

Vibrio alginolyticus belongs to gram-negative opportunistic pathogen realm infecting humans and aquatic animals causing severe economic losses. The (p)ppGpp-mediated stringent response is corroborated to stress adaptation and virulence of pathogenic mechanisms. Limited reports are documented for the intricate assessment of (p)ppGpp synthetase genes in combating various stress adaptation and elucidation of virulence in V. alginolyticus remains unraveled. The present assessment comprises of generation of deletion mutants in the (p)ppGpp-deficient strains, ΔrelA (relA gene single mutant) and ΔrelAΔspoT (relA and spoT genes double mutant), and the complemented strains, ΔrelA+ and ΔrelAΔspoT+, were constructed to investigate the pivotal roles of (p)ppGpp synthetase genes in V. alginolyticus, respectively. Amino acid sequence alignment analysis initially revealed that RelA and SpoT possess relatively conserved domains and synthetase activity. Hydrolase activity was emancipated by SpoT alone showing variant mode of action. Compared with the wild type and complemented strains, the relA-deficient strain was more sensitive to amino acid starvation and mupirocin. Interestingly, the deletion of spoT resulted in a significant growth deficiency supplemented with bile salts, 3 % ethanol and heat shock. Rapid growth was observed in the stationary phase upon exposure to cold stress and lower doses of ethanol. Subsequently, disruption of (p)ppGpp synthetase genes caused the decline in swimming motility, enhanced biofilm formation, cell aggregation of V. alginolyticus, and reduced mortality of Litopenaeus vannamei. The expression levels of some virulence-associated genes were quantified affirming consistency established by pleiotropic phenotypes. The results are evident for putative roles of (p)ppGpp synthetase genes attributing essential roles for environmental adaption and virulence regulation in V. alginolyticus.

9.
EBioMedicine ; 72: 103609, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34628353

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a severe psychiatric disorder that affects approximately 0.75% of the global population. Both genetic and environmental factors contribute to development of SCZ. SCZ tends to run in family while both genetic and environmental factor contribute to its etiology. Much evidence suggested that alterations in DNA methylations occurred in SCZ patients. METHODS: To investigate potential inheritable pattern of DNA methylation in SCZ family, we performed a genome-wide analysis of DNA methylation of peripheral blood samples from 106 Chinese SCZ family trios. Genome-wide DNA methylations were quantified by Agilent 1 × 244 k Human Methylation Microarray. FINDINGS: In this study, we proposed a loci inheritance frequency model that allows characterization of differential methylated regions as SCZ biomarkers. Based on this model, 112 hypermethylated and 125 hypomethylated regions were identified. Additionally, 121 hypermethylated and 139 hypomethylated genes were annotated. The results of functional enrichment analysis indicated that multiple differentially methylated genes (DMGs) involved in Notch/HH/Wnt signaling, MAPK signaling, GPCR signaling, immune response signaling. Notably, a number of hypomethylated genes were significantly enriched in cerebral cortex and functionally enriched in nervous system development. INTERPRETATION: Our findings not only validated previously discovered risk genes of SCZ but also identified novel candidate DMGs in SCZ. These results may further the understanding of altered DNA methylations in SCZ.

10.
Sci Rep ; 11(1): 20455, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650136

RESUMO

Genome-wide DNA methylation profiling have been used to find maternal CpG sites related to the occurrence of gestational diabetes mellitus (GDM). However, none of these differential sites found has been verified in a larger sample. Here, our aim was to evaluate whether first trimester changes in target CpG sites in the peripheral blood of pregnancy women predict subsequent development of GDM. This nested case-control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites of 80 GDM cases and 80 matched healthy controls during the early pregnancy (10-15 weeks) were assessed using MethylTarget sequencing. The best cut-off level for methylation of CpG site was determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at another 6 CpG sites were significantly lower (FDR < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for the occurrence of GDM. After adjusting for possible confounders, the hypermethylation status of CpG site 68167324 (OR = 3.168, 1.038-9.666) and 24837915 (OR = 5.232, 1.659-16.506) was identified as more strongly associated with GDM; meanwhile, the hypermethylation of CpG site 157130156 (OR = 0.361, 0.135-0.966) and 89438648 (OR = 0.206, 0.065-0.655) might indicate lower risk of GDM. The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester may be associated with GDM pathogenesis, and has potential as a predictor of GDM.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34651193

RESUMO

BACKGROUND: Malaria is one of the most serious global problems. The objective of this study is to assess whether intermittent preventive treatment (IPT) using artemisinin-based combination therapies (ACTs) was a promising alternative to IPT with sulphadoxine-pyrimethamine (IPT-SP). METHODS: We searched the following sources up to 12 August 2020: PubMed, The Cochrane Library, Embase, Web of Science, CNKI, CBM, VIP and WanFang Database from inception. The randomized controlled trials comparing SP with ACTs for malaria were included. Data were pooled using Stata.14 software. We performed subgroup analysis based on the different types of ACTs groups and participants. RESULTS: A total of 13 studies comprising 5180 people were included. The meta-analysis showed that ACTs had the lower risk of number of any parasitemia (RR=0.46; 95% CI 0.22 to 0.96, p=0.039; I2=90.50%, p<0.001), early treatment failure (RR=0.17; 95% CI 0.06 to 0.48, p<0.001; I2=66.60%, p=0.011) and late treatment failure (RR=0.34; 95% CI 0.13 to 0.92, p<0.001; I2=87.80%, p<0.001) compared with SP. There was no significant difference in adequate clinical response, average hemoglobin and adverse neonatal outcomes. CONCLUSION: Combinations with ACTs appear promising as suitable alternatives for IPT-SP.

12.
World J Surg Oncol ; 19(1): 262, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470640

RESUMO

BACKGROUND: This study aimed to investigate the correlation between miRNA-216b expression in patients with non-small cell lung cancer (NSCLC) and 18F-fluorodeoxyglucose (FDG) uptake by PET/CT and to explore the clinical application value of 18F-FDG PET/CT in miRNA-216b based on therapy for NSCLC. METHODS: Eighty patients with NSCLC and 40 healthy subjects were enrolled in our study. The SUVmax of the lesion area by PET/CT imaging was calculated. SUVmax represented the highest concentration of 18F-FDG in the lesion. The expression of miRNA-216b in the plasma and fiber bronchoscopic puncture of NSCLC patients was detected by RT qPCR. Then Pearson correlation analysis was used to analyze the correlation between miRNA-216b expression and 18F-FDG uptake in patients with different types of NSCLC. RESULTS: Compared with healthy subjects, SUVmax of early adenocarcinoma and advanced adenocarcinoma were increased. Compared with healthy subjects, SUVmax of early squamous and advanced squamous were increased. And the SUVmax content of advanced adenocarcinoma and squamous cell carcinoma was higher than that of early adenocarcinoma and squamous cell carcinoma. Compared with healthy subjects, the expression of miRNA-216b in the plasma of patients with early and advanced adenocarcinoma was reduced, and the expression of miRNA-216b in the plasma of patients with early and advanced squamous cell carcinoma was reduced. Compared with adjacent tissues, the expression of miRNA-216b in early adenocarcinoma tissues and advanced adenocarcinoma tissues was reduced, and the expression in early squamous cell carcinoma and advanced squamous cell carcinoma was reduced. Pearson correlation analysis showed a negative correlation between SUVmax and miRNA-216b (plasma and tissue) in patients with four types of NSCLC. CONCLUSION: miRNA-216b expression was negatively correlated with 18F-FDG uptake in NSCLC. miRNA-216b could be used for the classification and staging of non-small cell lung cancer. 18F-FDG PET/CT may be used to evaluate the therapeutic response in application of miRNA-216b-based cancer treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares , MicroRNAs , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , MicroRNAs/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos
13.
J Colloid Interface Sci ; 606(Pt 2): 1745-1757, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34500172

RESUMO

Herein, the optional and controllable growth of Bi2S3 onto NH2-MIL-125 via covalent conjunction strategy was reported. The experimental results demonstrate that the obtained heterojunction exhibits boosting photocatalytic reduction CO2 and organic dye degradation. The 18-Bi2S3@NH2-MIL-125-SH displays the highest yield of 12.46 µmol g-1h-1 of CO, >13 times that of pure NH2-MIL-125. Meanwhile, the reaction kinetic of 18-Bi2S3@NH2-MIL-125-SH in the degradation of methylene blue is uppermost, which is 160 times than that of the commercial P25. The enhancement of photocatalytic performance could be ascribed to the covalent coordination-driven intimate interfacial interaction in n-scheme heterojunction. Meanwhile, the plausible mechanism was also investigated by UV-vis diffuse reflectance (UV-vis), photoluminescence (PL), electrochemical photocurrent, electron spin resonance (ESR) and electrochemical impedance spectroscopy (EIS).

14.
Acta Pharmacol Sin ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465912

RESUMO

Liver fibrosis is one of the most severe pathologic consequences of chronic liver diseases, and effective therapeutic strategies are urgently needed. Proton pump inhibitors (PPIs) are H+/K+-ATPase inhibitors and currently used to treat acid-related diseases such as gastric ulcers, which have shown other therapeutic effects in addition to inhibiting acid secretion. However, few studies have focused on PPIs from the perspective of inhibiting hepatic fibrosis. In the present study, we investigated the effects of pantoprazole (PPZ), a PPI, against liver fibrosis in a bile duct ligation (BDL) rat model, human hepatic stellate cell (HSC) line LX-2 and mouse primary HSCs (pHSCs), and explored the potential mechanisms underlying the effects of PPZ in vitro and in vivo. In BDL rats, administration of PPZ (150 mg· kg-1· d-1, i.p. for 14 d) significantly attenuated liver histopathological injury, collagen accumulation, and inflammatory responses, and suppressed fibrogenesis-associated gene expression including Col1a1, Acta2, Tgfß1, and Mmp-2. In LX-2 cells and mouse pHSCs, PPZ (100-300 µM) dose-dependently suppressed the levels of fibrogenic markers. We conducted transcriptome analysis and subsequent validation in PPZ-treated LX-2 cells, and revealed that PPZ inhibited the expression of Yes-associated protein (YAP) and its downstream targets such as CTGF, ID1, survivin, CYR61, and GLI2. Using YAP overexpression and silencing, we demonstrated that PPZ downregulated hepatic fibrogenic gene expression via YAP. Furthermore, we showed that PPZ promoted the proteasome-dependent degradation and ubiquitination of YAP, thus inhibiting HSC activation. Additionally, we showed that PPZ destabilized YAP by disrupting the interaction between a deubiquitinating enzyme OTUB2 and YAP, and subsequently blocked the progression of hepatic fibrosis.

15.
Urol Int ; : 1-10, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34515239

RESUMO

A number of studies reported that miR-224-5p is involved in a variety of cancer-related cellular processes, yet its physiological role in clear cell renal cell carcinoma (ccRCC) remains unclear. In order to clarify the function of miR-224-5p in ccRCC, real-time quantitative-PCR was conducted to compare the expression of miR-224-5p in human normal renal tubular epithelial cell lines and ccRCC cell lines first, and a strikingly upregulated expression was observed in ccRCC cell lines. Inhibition of miR-224-5p expression by microRNA inhibitors could inhibit the proliferation, migration, and invasion of ccRCC cells. Besides, it was validated by dual-luciferase assay in which miR-224-5p directly targeted OCLN gene. The expression of OCLN was downregulated in ccRCC cells, and overexpression of miR-224-5p could inhibit the mRNA and protein expression levels of OCLN. Overexpression of OCLN could reduce the proliferation, migration, and invasion of ccRCC cells, while overexpressed miR-224-5p could partially reverse that inhibitory effect. Therefore, the promotive effect of miR-224-5p on the proliferation, invasion, and migration of ccRCC cell lines was at least partly due to the inhibition of OCLN expression. These findings highlighted the important function of miR-224-5p, which was promoting cell proliferation, migration, and invasion by downregulating OCLN, in the pathogenesis of ccRCC, and provided a potential treatment strategy.

16.
Mol Cancer ; 20(1): 117, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34511114

RESUMO

As an important medium of intercellular communication, exosomes play an important role in information transmission between tumor cells and their microenvironment. Tumor metastasis is a serious influencing factor for poor treatment effect and shortened survival. Lung cancer is a major malignant tumor that seriously threatens human health. The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis. Many studies have shown that tumor-derived exosomes promote lung cancer development through a number of processes. By promoting epithelial-mesenchymal transition of tumor cells, they induce angiogenesis, establishment of the pretransfer microenvironment, and immune escape. This understanding enables researchers to better understand the mechanism of lung cancer metastasis and explore new treatments for clinical application. In this article, we systematically review current research progress of tumor-derived exosomes in metastasis of lung cancer. Although positive progress has been made toward understanding the mechanism of exosomes in lung cancer metastasis, systematic basic research and clinical translational research remains lacking and are needed to translate our scientific understanding toward applications in the clinical diagnosis and treatment of lung cancer metastasis in the near future.

17.
Helicobacter ; : e12852, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510644

RESUMO

OBJECTIVE: To update and evaluate the recurrence rate of Helicobacter pylori (H. pylori) eradication therapy in recent 10 years. METHODS: A systematic search of PubMed, Embase, Cochrane library, and Web of science was performed to identify the studies of recurrence rate of H. pylori published from 2010 to 2019. Stata 15.0 was used for analysis. RESULTS: A total of 31 studies (16,797 participants) were analyzed. The recurrence rate of H. pylori was 9% (95% CI, 8-11%), and it showed an upward trend with the time elapsed after eradication. The annual recurrence rate was 4%, and there was a stable trend with the time elapsed after eradication. Subgroup analyses showed that the recurrence rate of H. pylori eradication by triple therapy was higher than that of quadruple therapy (14% [95% CI, 9-19] vs 12% [95% CI, 7-17]); urban was higher than that of rural (8% [95% CI, 1-14] vs 5% [95% CI, 1-9]); males were higher than that of females (11% [95% CI, 8-14] vs 10% [95% CI, 7-14]); Europe had the highest recurrence rate (16% [95% CI, -1 to 42]), and Africa had the lowest (1% [95% CI, 0-2]). The recurrence rate ofH. pylori was inversely related to the human development index. CONCLUSIONS: The recurrence rate of H. pylori showed an increasing trend in recent 10 years, and it is still a knotty public health problem worldwide. The recurrence rate of H. pylori showed an upward trend with the time elapsed after eradication, and the recurrence rate of H. pylori varies by area, gender, and eradication methods.

18.
Comput Math Methods Med ; 2021: 2448782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552658

RESUMO

In China, lung cancer is one of the leading causes of death among residents. Early diagnosis is of great significance for early interventional treatment and prolonging survival. PET/CT uses positron radiopharmaceuticals to observe the physiological and biochemical changes of the drug and its metabolites in the body and finally diagnoses the disease. 18F-FDG is a commonly used imaging agent, but its short isotopic half-life limits clinical high-throughput testing. This study retrospectively analyzed the imaging material of 100 lung cancer patients pathologically confirmed. Patients with lymph node metastasis were classified into the LM group (n = 30 cases), and those with no lymph node metastasis were classified into the NLM group (n = 70 cases). The results showed that MRI of superparamagnetic nanoferric oxide was better than diagnosis of lung cancer by the 18F-FDG PET/CT and had a high predictive power for lymph node metastasis. These turned out to be high-value lung cancer diagnosis of superparamagnetic nanoferric oxide MRI and high-capacity lymph node metastasis prediction of 18F-FDG PET/CT, which were worthy of implementation.

19.
J Biol Chem ; : 101222, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34560101

RESUMO

Intraneuronal neurofibrillary tangles composed of Tau aggregates have been widely accepted as an important pathological hallmark of Alzheimer's disease. A current therapeutic avenue for treating Alzheimer's disease is aimed at inhibiting Tau accumulation with small molecules such as natural flavonoids. Liquid-liquid phase separation (LLPS) of Tau can lead to its aggregation, and Tau aggregates can then be degraded by autophagy. However, it is unclear whether natural flavonoids modulate the formation of phase-separated Tau droplets or promote autophagy and Tau clearance. Here, using confocal microscopy and fluorescence recovery after photobleaching assays, we report that a natural antioxidant flavonoid compound myricetin slows LLPS of full-length human Tau, shifting the equilibrium phase boundary to a higher protein concentration. This natural flavonoid also significantly inhibits pathological phosphorylation and abnormal aggregation of Tau in neuronal cells, and blocks mitochondrial damage and apoptosis induced by Tau aggregation. Importantly, using co-immunoprecipitation and Western blotting, we show that treatment of cells with myricetin stabilizes the interaction between Tau and autophagy-related protein 5 (ATG5) to promote clearance of phosphorylated Tau to indirectly limit its aggregation. Consistently, this natural flavonoid inhibits mTOR pathway, activates ATG5-dependent Tau autophagy, and almost completely suppresses Tau toxicity in neuronal cells. Collectively, these results demonstrate how LLPS and abnormal aggregation of Tau are inhibited by natural flavonoids, bridging the gap between Tau LLPS and aggregation in neuronal cells, and also establish that myricetin could act as an ATG5-dependent autophagic activator to ameliorate the pathogenesis of Alzheimer's disease.

20.
BMC Neurol ; 21(1): 371, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563155

RESUMO

BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS. METHODS: We searched several databases to identify relevant studies, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Central Register of Controlled Trials(CENTRAL). The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. RESULTS: Six randomised controlled trials (RCTs) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.76 points (95 % CI, -4.08 to -1.45, p < 0.001) after treatment with 3, 4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.34 mV, 95 % CI, 0.98 to 1.70, p < 0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity. CONCLUSIONS: The pooled results of RCTs demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

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