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1.
J Magn Reson Imaging ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664744

RESUMO

BACKGROUND: The relationship between osteoporosis and intervertebral disc (IVD) degeneration remains controversial. Novel quantitative Dixon (Q-Dixon) and GRAPPATINI T2 mapping techniques have shown potential for evaluating the biochemical components of the spine. PURPOSE: To investigate the correlation of osteoporosis with IVD degeneration in postmenopausal women. STUDY TYPE: Prospective. SUBJECTS: A total of 105 postmenopausal females (mean age, 65 years; mean body mass index, 26 kg/m2 ). FIELD STRENGTH/SEQUENCE: 3 T; sagittal; 6-echo Q-Dixon, multiecho spin-echo GRAPPATINI T2 mapping, turbo spin echo (TSE) T1-weighted and TSE T2-weighted sequences. ASSESSMENT: The subjects were divided into normal (N = 47), osteopenia (N = 28), and osteoporosis (N = 30) groups according to quantitative computed tomography examination. The Pfirrmann grade of each IVD was obtained. Region of interest analysis was performed separately by two radiologists (X.L., with 10 years of experience, and S.C., with 20 years of experience) on a fat fraction map and T2 map to calculate the bone marrow fat fraction (BMFF) from the L1 to L5 vertebrae and the T2 values of each adjacent IVD separately. STATISTICAL TESTS: One-way analysis of variance, post-hoc comparisons, and Kruskal-Wallis H tests were performed to evaluate the differences in the magnetic resonance imaging parameters between the groups. The relationships between BMFF and the IVD features were analyzed using the Spearman correlation analysis and linear regression models. RESULTS: There were significant differences in BMFF among the three groups. The osteoporosis group had higher BMFF values (64.5 ± 5.9%). No significant correlation was found between BMFF and Pfirrmann grade (r = 0.251, P = 0.06). BMFF was significantly negatively correlated with the T2 of the adjacent IVD from L1 to L3 (r = -0.731; r = -0.637; r = -0.547), while significant weak correlations were found at the L4 to L5 levels (r = -0.337; r = -0.278). DATA CONCLUSION: This study demonstrated that osteoporosis is associated with IVD degeneration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 4.

2.
Andrologia ; : e14275, 2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34658054

RESUMO

The updated meta-analysis was conducted to further verify the effect of varicocele on sperm DNA damage, supplying clinicians and researchers with high-grade evidence. The sperm DNA damage was evaluated by DNA fragmentation index (DFI), associated with the male fertility capability tightly. PubMed, Web of Science and Cochrane Library were searched extensively for eligible studies with the search terms: varicocele, sperm DNA and sperm DNA damage. Finally, a total of 12 studies were included in our meta-analysis with a total of 845 patients diagnosed with varicocele and 2,377 healthy controls. A statistical difference of DFI between varicocele patients and healthy controls was found after pooling the data ((Standardised mean difference) SMD: 1.40, 95%CI: 0.83-1.98, p < .0001), using the random effect model. We conducted subgroup analysis according to study region (Brazil and Other countries), detection methods of DFI (TUNEL, Comet, and SCSA), sample size (<50 and >50) and age (<30 and >30 years), based on substantial heterogeneity among eligible studies. The stability of pooled results was verified by sensitivity analysis. All these statistical analyses were conducted using Stata version 16.0. In conclusion, patients diagnosed with clinical varicocele had higher DFI than healthy controls, which means varicocele could impair sperm DNA, consequently the fertility potential of affected men.

3.
Plant Physiol ; 186(4): 2078-2092, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34618111

RESUMO

Tomato (Solanum lycopersicum) is a highly valuable fruit crop, and yield is one of the most important agronomic traits. However, the genetic architecture underlying tomato yield-related traits has not been fully addressed. Based on ∼4.4 million single nucleotide polymorphisms obtained from 605 diverse accessions, we performed a comprehensive genome-wide association study for 27 agronomic traits in tomato. A total of 239 significant associations corresponding to 129 loci, harboring many previously reported and additional genes related to vegetative and reproductive development, were identified, and these loci explained an average of ∼8.8% of the phenotypic variance. A total of 51 loci associated with 25 traits have been under selection during tomato domestication and improvement. Furthermore, a candidate gene, Sl-ACTIVATED MALATE TRANSPORTER15, that encodes an aluminum-activated malate transporter was functionally characterized and shown to act as a pivotal regulator of leaf stomata formation, thereby affecting photosynthesis and drought resistance. This study provides valuable information for tomato genetic research and breeding.

4.
Anal Chim Acta ; 1178: 338847, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34482880

RESUMO

Photodynamic therapy has been generally developed and approved as a promising theranostic technique in recent years, which requires photosensitizers to bear high efficiency of reactive oxygen species production, precisely targeting ability and excellent biocompatibility. The real-time monitoring the microenvironments such as viscosity dynamic involved in mitophagy mediated by photodynamic therapy is significantly important to understand therapeutic process but barely reported. In this work, a pyridinium-functionalized triphenylamine derivative, (E)-4-(2-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)vinyl)-1-methylpyridin-1-ium iodide (Mito-I), was exploited as photosensitizer for mitochondria-targeted photodynamic therapy and as fluorescent probe for imaging the mitochondrial viscosity dynamic during mitophagy simultaneously. The results indicated that the additional phenyl ring in Mito-I was beneficial to promote its efficiency of singlet oxygen production. The excellent capability of targeting mitochondria and singlet oxygen generation allowed Mito-I for the specifically mitochondria-targeted photodynamic therapy. Moreover, Mito-I displayed off-on fluorescence response to viscosity with high selectivity and sensitivity. The observed enhancement in fluorescence intensity of Mito-I revealed the increasingly mitochondrial viscosity during mitophagy mediated by the photodynamic therapy of Mito-I. As a result, this work presents a rare example to realize the mitochondria-targeting photodynamic therapy as well as the real-time monitoring viscosity dynamic during mitophagy, which is of great importance for the basic medical research involved in photodynamic therapy.


Assuntos
Mitofagia , Fotoquimioterapia , Mitocôndrias , Fármacos Fotossensibilizantes/farmacologia , Viscosidade
5.
Plants (Basel) ; 10(9)2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34579490

RESUMO

Acid rain deposition (AR) has long-lasting implications for the community stability and biodiversity conservation in southwest China. Acer catalpifolium is a critically endangered species in the rain zone of Western China where AR occurs frequently. To understand the effects of AR on the morphology and physiology of A. catalpifolium, we conducted an acid stress simulation experiment for 1.5 years. The morphological, physiological, and photosynthetic responses of A. catalpifolium to the acidity, composition, and deposition pattern of acid stress was observed. The results showed that simulated acid stress can promote the growth of A. catalpifolium via the soil application mode. The growth improvement of A. catalpifolium under nitric-balanced acid rain via the soil application mode was greater than that of sulfuric-dominated acid rain via the soil application mode. On the contrary, the growth of A. catalpifolium was significantly inhibited by acid stress and the inhibition increased with the acidity of acid stress applied via leaf spraying. The inhibitory impacts of nitric-balanced acid rain via the leaf spraying of A. catalpifolium were greater than that of sulfur-dominant acid rain via leaf spraying. The observations presented in this work can be utilized for considering potential population restoration plans for A. catalpifolium, as well as the forests in southwest China.

6.
Cells ; 10(9)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34571920

RESUMO

General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the expression of many inflammatory mediators. NF-κB is likely to be involved in the mechanism of most inflammatory diseases. We discovered a specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), about 20 years ago by molecular design from a natural product. It directly binds to and inactivates NF-κB components. It has been widely used to suppress cellular and animal inflammatory disease models and was shown to be potent in vivo anti-inflammatory activity without any toxicity. We have prepared ointment of DHMEQ for the treatment of severe skin inflammation. It inhibited inflammatory cytokine expressions and lowered the clinical score in mouse models of atopic dermatitis. Intraperitoneal (IP) administration of DHMEQ ameliorated various disease models of inflammation, such as rheumatoid arthritis, sepsis, and also graft rejection. It has been suggested that inflammatory cells in the peritoneal cavity would be important for most peripheral inflammation. In the present review, we describe the synthesis, mechanism of action, and cellular and in vivo anti-inflammatory activities and discuss the clinical use of DHMEQ for inflammatory diseases.

7.
Int Immunopharmacol ; 99: 108016, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34385029

RESUMO

OBJECTIVE: The purpose of this study was to explore the relationship between pretreatment cytokine status and overall survival and establish a prognostic nomogram incorporating cytokines in newly diagnosed multiple myeloma (NDMM) patients. METHODS: A total of 121 patients with NDMM from the Wuhan Union Hospital were included in our study. Patient serum levels of cytokines, including macrophage inflammatory protein 1 alpha (MIP-1α), migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor-α (VEGF-α), monocyte chemoattractant protein-1 (MCP-1) and soluble interleukins IL-17A, IL-6, IL-21 and IL-10 were assessed before treatment. Based on the results of the multivariate Cox proportional hazards model, we developed a prognostic nomogram. We used the concordance index (C-index) and a calibration curve to measure the predictive performance of the nomogram. RESULTS: Three important variables (lactate dehydrogenase, MIP-1α and creatinine) were incorporated in the nomogram using multivariate Cox analysis. The 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 83.8% and 21.8% in the low-risk group of the nomogram and 17.4% and 8.4% in the high-risk group, respectively. The C-index of the nomogram for OS prediction was 0.80 (95% CI: 0.68-0.92), showing superiority over the predictive power of the Durie-Salmon staging system (C-index = 0.58; 95% CI: 0.49-0.67), International Staging System (C-index = 0.70; 95% CI: 0.61-0.79) and Revised-International Staging System (C-index = 0.71; 95% CI: 0.63-0.80). The calibration curve showed that the nomogram accurately predicted the 1-year, 2-year and 3-year OS of NDMM patients. CONCLUSION: The established nomogram provides accurate and individualized OS risk estimation for NDMM patients.

8.
Plant Cell ; 33(10): 3293-3308, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34338777

RESUMO

The degree of stigma exsertion has a major influence on self-pollination efficiency in tomato, and its improvement is essential for raising productivity and for fixing advantageous traits in cultivated tomato. To study the evolution of stigma exsertion degree in tomato, we searched for genes associated with this trait and other aspects of flower morphology, including the lengths of anthers, styles, and ovaries. We performed a genome-wide association on 277 tomato accessions and discovered a novel stigma exsertion gene (SE3.1). We reannotated the structure of the gene, which encodes a C2H2-type zinc finger transcription factor. A mutation of the lead single nucleotide polymorphism creates a premature termination codon in SE3.1 and an inserted stigma in cultivated tomatoes. SE3.1 is essential for the conversion of flush stigmas to inserted stigmas. This conversion has a major impact on the rate of self-fertilization. Intriguingly, we found that both SE3.1 and Style2.1 contribute to the transition from stigma exsertion to insertion during the domestication and improvement of tomato. Style2.1 controls the first step of exserted stigmas to flush stigmas, and SE3.1 controls the second step of flush stigmas to inserted stigmas. We provide molecular details for the two-step process that controls the transition from stigma exsertion to insertion, which is of great agronomic importance in tomato.

9.
ACS Omega ; 6(31): 20569-20576, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34396002

RESUMO

Blue indigo dye, an important natural colorant, is used for textiles and food additives worldwide, while another red isomer, indirubin, is the major active ingredient of a traditional Chinese medicine named "Danggui Longhui Wan" for treating various diseases including granulocytic leukemia, cancer, and Alzheimer's disease. In this work, we constructed a new and highly efficient indigoid production system by optimizing a novel terpenoid cyclase, XiaI, from the xiamycin biosynthetic pathway. Through introducing the flavin-reducing enzyme Fre, tryptophan-lysing and -importing enzymes TnaA and TnaB, and H2O2-degrading enzyme KatE and optimizing the fermentation parameters including temperature, the concentration of isopropyl-ß-d-thiogalactopyranoside, and feeding of the l-tryptophan precursor, the final maximum productivity of indigoids by the recombinant strain Escherichia coli BL21(DE3) (XiaI-Fre-TnaAB-KatE) was apparently improved to 101.9 mg/L, an approximately 60-fold improvement to that of the starting strain E. coli BL21(DE3) (XiaI) (1.7 mg/L). In addition, when the fermentation system was enlarged to 1 L in the flask (feeding with 5 mM tryptophan and 10 mM 2-hydroxyindole), the indigoid productivity further increased to 276.7 mg/L at 48 h, including an indigo productivity of 26.0 mg/L and an indirubin productivity of 250.7 mg/L, which has been the highest productivity of indirubin so far. This work provided a basis for the commercial production of bio-indigo and the clinical drug indirubin in the future.

10.
Eur J Med Chem ; 224: 113697, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34273662

RESUMO

ß2-Agonists that bind to plasmalemmal ß2-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their ß2-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC50 < 20 pM) and selective ß2-agonists among the compounds tested. They behaved as partial ß2-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are ß2-agonists with potential applicability in chronic respiratory diseases.

11.
J Sci Med Sport ; 24(12): 1240-1244, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34281769

RESUMO

OBJECTIVES: The deficits in sensory pathways caused by peripheral edema, pain, and inflammation of the damaged ligaments may induce maladaptive changes within the central nervous system. The purpose of this study was to determine whether patients with lateral ankle instability (LAI) exhibit morphological differences of brain grey matter when compared with healthy controls, and then assess the relationships between the observed differences and the characteristics of patients. DESIGN: Cross-sectional. METHODS: Thirty patients with LAI and 32 healthy controls without LAI underwent MRI scans using anatomical T1 sequences. A voxel-wise general linear model was used to compare the grey matter volume throughout the whole brain between patients and controls. Linear regression analyses were performed for the grey matter volume within the significant clusters to assess their relationship with age, sex, the existence of acute injury, pain level, sports activity level, and the duration of LAI within the patient group. RESULTS: The grey matter volume of a cluster within the cerebellar vermis (Vermis_4_5 in automated anatomical labeling template) was significantly reduced in patients with LAI (Gaussian Random Field corrections with two-tailed p-cluster < 0.05 and p-voxel < 0.001). Multivariate linear regression analysis revealed that the duration of LAI tended to be passively associated with the grey matter volume of this LAI-related vermal cluster (p = 0.092). CONCLUSIONS: Participants with LAI exhibited a reduced grey matter volume of a cluster within the cerebellar vermis compared with participants without LAI, and the degree of volume reduction tended to be positively associated with the duration of LAI.

12.
Hortic Res ; 8(1): 148, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34193825

RESUMO

There is a critical need to identify germplasm resources and genes that promote cold tolerance of tomato because global tomato production is threatened by cold stress. We found that the expression of an F-box gene family member named ShPP2-1 from Solanum habrochaites is cold inducible and studied its contribution to cold tolerance. Overexpression of ShPP2-1 in cultivated tomato (AC) reduced cold tolerance by intensifying damage to cell membranes. To explore the underlying molecular mechanism, we conducted a yeast two-hybrid library screen and found that a protein containing ACT domain repeats named ACR11A interacts with PP2-1. Overexpression of SlACR11A in AC enhanced the cold tolerance of seedlings and germinating seeds. Cold tolerance decreased in tomato plants that overexpressed both of these genes. Additionally, we performed seed germination experiments in the cold with 177 tomato accessions and identified two alleles of SlACR11A that differ in one single-nucleotide polymorphism. We found that one of these alleles, SlACR11AG, is significantly enriched in cold-tolerant tomato plants. Taken together, our findings indicate that the combination of low expression levels of PP2-1 and high expression levels of ACR11A can promote cold tolerance. These genes may therefore serve as direct targets for both genetic engineering and improvement projects that aim to enhance the cold tolerance of tomato.

13.
Andrologia ; 53(9): e14158, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34191302

RESUMO

Kidney transplantation has been considered as the most effective therapy for patients with end-stage renal disease. However, less attention was attached to infertility. The present meta-analysis was conducted to compare the semen quality between patients with dialysis and patients after kidney transplantation. An extensive search in MEDLINE, PubMed and Web of Science was conducted from inception to March 2021. The data extracted for meta-analysis included sample size and characteristics, main reported outcomes like semen quality and hormone levels. For the semen quality and hormone levels, the standardized mean difference (SMD) and 95% confidential interval (CI) were calculated to evaluate the effect size. Finally, 5 studies were included in meta-analysis. Kidney transplantation could improve the sperm density of patients undergoing dialysis (SMD 1.58 [0.02, 3.15]). Additionally, the sperm motility was also improved after the kidney transplantation (SMD 3.26 [0.73, 5.79]). The sperm density of kidney transplantation patients was lower than that in healthy subjects (SMD -0.75 [-1.42, -0.07]), same as the sperm motility (SMD -0.50 [-0.80, -0.20]). Our meta-analysis suggests kidney transplantation could improve semen quality of patients with ESRD, including sperm density and sperm motility. Of note, semen quality of renal transplantation recipient still is inferior to healthy subjects.


Assuntos
Transplante de Rim , Humanos , Masculino , Diálise Renal , Sêmen , Análise do Sêmen , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides
14.
Hortic Res ; 8(1): 128, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34059638

RESUMO

In plants, chloroplasts are the sites at which photosynthesis occurs, and an increased abundance of chloroplasts increases the nutritional quality of plants and the resultant color of fruits. However, the molecular mechanisms underlying chlorophyll synthesis and chloroplast development in tomato fruits remain unknown. In this study, we isolated a chlorophyll-deficient mutant, reduced chlorophyll mutant 1 (rcm1), by ethylmethanesulfonate mutagenesis; this mutant produced yellowish fruits with altered chloroplast development. MutMap revealed that Solyc08g005010 is the causal gene underlying the rcm1 mutant phenotype. A single-nucleotide base substitution in the second exon of SlRCM1 results in premature termination of its translated protein. SlRCM1 encodes a chloroplast-targeted metalloendopeptidase that is orthologous to the BCM1 protein of Arabidopsis and the stay-green G protein of soybean (Glycine max L. Merr.). Notably, the yellowish phenotype of the lutescent1 mutant can be restored with the allele of SlRCM1 from wild-type tomato. In contrast, knockout of SlRCM1 by the CRISPR/Cas9 system in Alisa Craig yielded yellowish fruits at the mature green stage, as was the case for lutescent1. Amino acid sequence alignment and functional complementation assays showed that SlRCM1 is indeed Lutescent1. These findings provide new insights into the regulation of chloroplast development in tomato fruits.

15.
J Magn Reson Imaging ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34189805

RESUMO

BACKGROUND: Anatomic repair is widely accepted as the primary surgical treatment for chronic lateral ankle instability (CLAI). T2-mapping is a powerful tool for quantitative assessment of biochemical changes in cartilage matrix. PURPOSE: To longitudinally evaluate cartilage matrix changes in the hindfoot joints of CLAI patients before and after anatomic repair by using T2-mapping with magnetic resonance imaging (MRI). STUDY TYPE: Prospective. SUBJECTS: Thirty-two CLAI patients (males/females = 20/12) and 21 healthy controls (males/females = 13/7). FIELD STRENGTH/SEQUENCE: 3 T; sagittal multi-echo spin-echo technique (T2-mapping), coronal, sagittal, and axial spin-echo PD-FS, and sagittal T1WI sequences. ASSESSMENT: MRI examinations were performed in CLAI patients at baseline (prior to surgery) and 3 years after anatomic repair and in healthy controls. On T2-maps, the hindfoot joints were segmented into 16 cartilage subregions. The T2 value of each subregion was measured. All patients were evaluated with the American Orthopedic Foot and Ankle Society (AOFAS) scale at baseline and after surgery. STATISTICAL TESTS: Analysis of variance (ANOVA) and Student's t-test were used. The differences corresponding to P < 0.05 were considered statistically significant. RESULTS: At baseline, the T2 values in most cartilage subregions of talar dome and medial posterior subtalar joint (pSTJ) were higher in CLAI patients than in healthy controls. After surgery, only the T2 value of anteriomedial talar dome decreased from that at baseline (31.11 ± 3.88 msec vs. 34.27 ± 5.30 msec). The T2 values of other subregions with elevated T2 values remained higher than healthy controls. There were no significant differences in T2 values in the midtarsal joints between CLAI patients and healthy controls (P = 0.262, 0.104, 0.169, 0.103). Postoperatively, the patients' AOFAS scores improved significantly from 67.81 to 89.13. DATA CONCLUSION: CLAI patients exhibited elevated T2 values in most subregions of talar dome and medial pSTJ. After anatomic repair, although the patients exhibited good clinical outcomes, the elevated T2 values could not be fully recovered. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 4.

16.
Andrologia ; 53(8): e14149, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34151474

RESUMO

While the intima-media thickness (IMT) of the cavernous artery was used for diagnosis for vascular erectile dysfunction (ED) with more accuracy than the peak systolic velocity, the role of the IMT in predicting treatment responses remained unexamined. A total of 136 patients with ED were enrolled. The baseline clinical and laboratory characteristics were collected. Penile Doppler ultrasonography (PDU) was performed on all patients by a blinded sonographer. Sildenafil was administrated to all patients with an adjusted dose of 50 or 100 mg on demand over a period of 3 months. A follow-up was conducted on all patients using the Erectile Hardness Score (EHS) questionnaire along with the visual and tactile version of the standardised EHS tool. The peak systolic velocity (PSV) and IMT were compared between sildenafil responders and sildenafil nonresponders, while receiver operator characteristic (ROC) curves were used to calculate the cut-off values and compare the test power respectively. There was no statistical difference from the baseline characteristics. The IMT of cavernous artery was more accurate than PSV to predict the sildenafil response (AUC = 0.809, 0.626 respectively). IMT could predict sildenafil responders more accurately than PSV, and the cut-off value of the IMT of the cavernous artery was less than 0.22 mm.


Assuntos
Espessura Intima-Media Carotídea , Disfunção Erétil , Artérias/diagnóstico por imagem , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Pênis/diagnóstico por imagem , Citrato de Sildenafila/uso terapêutico
17.
Sex Med ; 9(3): 100356, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34051538

RESUMO

INTRODUCTION: The association between folic acid (FA) and erectile dysfunction (ED) was contradictory in the published original articles, and no meta-analysis was conducted to pool these data. AIM: To verify the role of FA in the pathology of ED and explore the treatment efficacy of FA for ED patients. METHODS: An extensive search was performed on PubMed, Cochrane Library, and Web of Science to obtain all relevant studies published up to October 31, 2020. Studies comparing the serum FA level between ED patients and healthy controls, or comparing the score of the IIEF-5, or IIEF before and after folic acid therapy alone or combination in ED patient were eligible for our meta-analysis. The Newcastle-Ottawa Scales (NOS) was used to qualify included studies. MAIN OUTCOME MEASURES: The standardized mean differences (SMD) and their corresponding 95% confidence intervals (95% CIs) were calculated to pool our data. RESULTS: Nine studies were eligible for our meta-analysis to verify the association between FA and ED, and to explore the treatment efficacy of FA for ED patients. The pooled SMD of the FA level difference between ED patients and healthy subjects was -0.94 (95% CI: -1.59, -0.30, P = .004). Moreover, the level of folic acid in healthy subjects, Mild ED patients, Moderate ED patients and Severe ED patients was 11.847 (95%CI = 9.671, 14.022), 9.496 (95%CI = 8.425, 10.567), 6.597 (95%CI = 5.187, 8.007) and 5.623 (95%CI = 3.535, 7.711) respectively. The SMD of changes in score of IIEF-5 was 1.89 with 95%CI (1.60, 2.17) after FA administration in ED patients. Our analysis also showed that combination therapy of FA plus tadalafil changed the score of IIEF with 0.90 (95%CI = 0.44, 1.36) comparing to combination of placebo plus tadalafil. CONCLUSION: This novel meta-analysis demonstrated that FA was an independent risk factor for ED and FA supplement may have potentially positive effects in the treatment of ED patients. Zhang Y, Zhang W, Dai Y, et al. Serum Folic Acid and Erectile Dysfunction: A Systematic Review and Meta-Analysis. Sex Med 2021;9:100356.

18.
Neuroscience ; 465: 85-94, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33895342

RESUMO

Autism spectrum disorder (ASD) is a widespread, complex and serious neurodevelopmental disorder. Complex genetic and environmental factors are thought to contribute to the development of ASD. Genome-wide association analysis has identified multiple autism-related genes. Mutation of the phosphatase and tensin homolog (Pten) is closely related to autism and accounts for 5-17% of cases of autism. However, the detailed mechanism is still unclear. Recently, mitochondrial dysfunction was tightly associated with ASD pathogenesis, such as developmental degeneration, learning and various behavioral disorders. The mitochondrial DNA (mtDNA) copy number in children with autism is also significantly increased. The correlation between Pten and mitochondrial dysfunction in autism is still unknown. In this study, we examined how Pten regulates mitochondrial biogenesis through the AKT/GSK-3ß/PGC-1α signaling pathways. We found that PTEN could dephosphorylate AKT to inhibit its activity, leading to decreased GSK3ß phosphorylation. This decrease in GSK3ß phosphorylation, which could activate itself, increased PGC-1α phosphorylation to promote its degradation and then regulated mitochondrial biogenesis by NRF-1 and TFAM downstream of PGC-1α. In the Valproic acid (VPA) induced autism mouse model, the PTEN protein level was significantly decreased while PGC-1α and COX IV levels were increased in the hippocampus and cortex. Our data suggest that there is a correlation between PTEN and mitochondrial dysfunction and this correlation may be a potential mechanism of ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtorno do Espectro Autista/genética , Transtorno Autístico/genética , DNA Mitocondrial , Estudo de Associação Genômica Ampla , Glicogênio Sintase Quinase 3 beta , Humanos , Biogênese de Organelas , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
19.
Front Oncol ; 11: 632910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33747954

RESUMO

Background: Circulating tumor DNA (ctDNA) has offered a minimally invasive approach for the detection and measurement of cancer. However, its diagnostic and prognostic value in hematological malignancies remains unclear. Materials and methods: Pubmed, Embase, and Cochrane Library were searched for relating literature. Diagnostic accuracy variables and disease progression prediction data were pooled by the Meta-Disc version 1.4 software. Review Manager version 5.4 software was applied for prognostic data analysis. Results: A total of 11 studies met our inclusion criteria. In terms of diagnosis, the pooled sensitivity and specificity were 0.51 (95% confidence intervals (CI) 0.38-0.64) and 0.96 (95% CI 0.88-1.00), respectively. The AUSROC (area under the SROC) curve was 0.89 (95%CI 0.75-1.03). When it comes to the prediction of disease progression, the overall sensitivity and specificity was 0.83 (95% CI 0.67-0.94) and 0.98 (95% CI 0.93-1.00), respectively. Moreover, a significant association also existed between the presence of ctDNA and worse progression-free survival (HR 2.63, 95% CI 1.27-5.43, p = 0.009), as well as overall survival (HR 2.92, 95% CI 1.53-5.57, p = 0.001). Conclusions: The use of ctDNA in clinical practice for hematological malignancies is promising, as it may not only contribute to diagnosis, but could also predict the prognosis of patients so as to guide treatment. In the future, more studies are needed to realize the standardization of sequencing techniques and improve the detection sensitivity of exploration methods.

20.
Front Oncol ; 11: 639528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33747963

RESUMO

Background: To investigate the prognostic value of circulating plasma cells (CPC) and establish novel nomograms to predict individual progression-free survival (PFS) as well as overall survival (OS) of patients with newly diagnosed multiple myeloma (NDMM). Methods: One hundred ninetyone NDMM patients in Wuhan Union Hospital from 2017.10 to 2020.8 were included in the study. The entire cohort was randomly divided into a training (n = 130) and a validation cohort (n = 61). Univariate and multivariate analyses were performed on the training cohort to establish nomograms for the prediction of survival outcomes, and the nomograms were validated by calibration curves. Results: When the cut-off value was 0.038%, CPC could well distinguish patients with higher tumor burden and lower response rates (P < 0.05), and could be used as an independent predictor of PFS and OS. Nomograms predicting PFS and OS were developed according to CPC, lactate dehydrogenase (LDH) and creatinine. The C-index and the area under receiver operating characteristic curves (AUC) of the nomograms showed excellent individually predictive effects in training cohort, validation cohort or entire cohort. Patients with total points of the nomograms ≤ 60.7 for PFS and 75.8 for OS could be defined as low-risk group and the remaining as high-risk group. The 2-year PFS and OS rates of patients in low-risk group was significantly higher than those in high-risk group (p < 0.001). Conclusions: CPC is an independent prognostic factor for NDMM patients. The proposed nomograms could provide individualized PFS and OS prediction and risk stratification.

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