Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.725
Filtrar
1.
Int J Biol Markers ; : 1724600819884722, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674884

RESUMO

OBJECTIVE: To investigate the role of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and P16 in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 95 paraffin-embedded samples of tumorous tissue of HNSCC were collected. Expression levels of PD-1, PD-L1, and P16 were determined by immunohistochemistry. RESULTS: A significantly higher proportion of PD-1 among patients infected with the human papillomavirus was found. PD-L1 expression is closely associated with the primary site of the tumor, postoperative recurrence, survival, PD-1 expression and P16 expression. Univariable analysis indicated that T stage, N stage, tumor node metastasis stage, tumor differentiation, and PD-L1 expression were all shown to be prognostic variables for overall survival in patients with HNSCC. In the multivariate analysis, only N stage (P = 0.010) and PD-L1 expression (P = 0.001) were found to be independent prognostic variables for overall survival. In addition, for disease recurrence, multivariate analysis showed that only PD-L1 expression was the associated independent risk factor. For the patients with negative PD-L1 expression, Kaplan-Meier analysis revealed that they had significantly worse outcomes in terms of overall survival (P = 0.001). Similarly, compared with the patients with positive PD-L1 expression, those with negative PD-L1 expression had a higher probability of recurrence (P = 0.026). CONCLUSIONS: The expression of PD-L1, PD-1, and P16 in HNSCC is significantly correlated. Human papillomavirus infection (P16 positive) is negatively related to postoperative recurrence. HNSCC patients with positive PD-L1/PD-1 expression tend to have better overall survival outcomes and lower probability of recurrence, providing more evidence for the PD-l-targeted immunotherapy of HNSCC.

2.
Clin Nutr ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31669001

RESUMO

BACKGROUND & AIMS: To investigate the association of VitD with GDM, and examine the potential modifying effect of prepregnancy BMI in Chinese pregnant women. METHODS: 3318 pregnant women underwent oral glucose tolerance test (OGTT) were selected from Zhoushan Pregnant Women Cohort. Plasma VitD levels were measured in the first (T1) and/or second trimester (T2). Multiple linear and logistic regression models were used for evaluating the association of VitD with GDM. RESULTS: Prepregnancy BMI was positively associated with all three time-point glucose of OGTT. 25(OH)D level in T1 (ß = -0.003) and T2 (ß = -0.004), and its change from T1 to T2 (ß = -0.004) were significantly and inversely associated with fasting blood glucose (FBG) of OGTT, but not 1-h and 2-h postload blood glucose of OGTT, respectively. The negative associations of VitD and FBG were stronger among overweight/obese women. VitD deficiency (25(OH)D < 20 ng/ml) in T2 was associated with an increased risk of GDM with increased FBG, GDM subtype 1 (OR: 2.10) and subtype 3 (OR: 2.19). Moreover, prepregnancy BMI modified this effect on GDM subtype 1 (BMI < 24: OR = 1.42; BMI ≥ 24: OR = 9.61, P for interaction = 0.002). Lower VitD increment from T1 to T2 was associated with a higher risk for GDM among overweight/obese women. Additionally, GDM prevalence fluctuated with the season, i.e. lower in summer/fall and higher in winter/spring. CONCLUSIONS: Maternal VitD deficiency was associated with a higher risk of GDM subtype with increased FBG, and the risk is much greater among overweight/obesity women. The lower the VitD increment during pregnancy, the greater the risk of GDM, especially in overweight/obesity women. Furthermore, seasonal variation of GDM may be exhibited as a critical confounder in the association of VitD and GDM.

3.
Environ Res ; 180: 108843, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31670082

RESUMO

BACKGROUND: Previous studies have shown that ambient air pollution exposure can increase the risk of type 2 diabetes mellitus (T2DM) significantly. In consideration of the common underlying pathophysiologic mechanisms, exposure to air pollution may also increase the risk of gestational diabetes mellitus (GDM), but the current evidence was inconsistent and has not well been systematically reviewed. Our goal was to perform a systematic review and meta-analysis assessing the association between air pollution exposure and GDM. METHODS: An extensive literature search was conducted in selected electronic databases for related human epidemiological studies published in English language. Summary effect estimates were calculated using random-effect models for a) risk per unit increase in continuous air pollutant concentration and b) risk of high versus low exposure level in individual study if each exposure that had been examined in ≥2 studies. We evaluated the heterogeneity using Cochran's Q test and quantified it by I2 statistic. Publication bias was also evaluated through the funnel plot when sufficient number of studies are available. RESULTS: A total of 11 studies evaluating the association between GDM and exposure to air pollution were identified finally. The summary odds ratio (OR) for incidence of GDM following a 10 µg/m3 increase in PM2.5 exposure during the second trimester was 1.04 (95% Confidence Interval (CI): 1.01, 1.09) and in NOx during the first trimester was 1.03 (95%CI: 1.00, 1.07) per 10 ppb increase, while for high versus low SO2 exposure during the second trimester was 1.25 (95%CI: 1.02, 1.53). High heterogeneity among study-specific results in majority of the analyses were observed, and attributed to different exposure assessment methods, populations, study locations, and covariates adjustment. Publication bias cannot be excluded because of the inclusion of small number of studies. CONCLUSIONS: The present study supports the evidence that air pollution exposure increases the risk the GDM, albeit the existence of high heterogeneity. Further studies are necessary to elaborate the suggestive associations. These results are of public health significance since worsening air pollution in developing countries has been expected to increase the risk of GDM development.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31604771

RESUMO

Many Gram-negative bacteria employ N-acylhomoserine lactones (AHLs) as quorum sensing (QS) signal molecules to regulate virulence expression in a density-dependent manner. Quorum quenching (QQ) via enzymatic inactivation of AHLs is a promising strategy to reduce bacterial infections and drug resistance. Herein, a thermostable AHL lactonase (AidB), which could degrade different AHLs, with or without a substitution of carbonyl or hydroxyl at the C-3 position, was identified from the soil bacterium Bosea sp. F3-2. Ultra-high performance liquid chromatography analysis demonstrated that AidB is an AHL lactonase that hydrolyzes the ester bond of the homoserine lactone ring. AidB was thermostable in the range 30 to 80 °C and showed maximum activity after pre-incubating at 60 °C for 30 min. The optimum temperature of AidB was 60 °C, and the enzyme could be stably stored in ddH2O at 4 °C or room temperature. AidB homologs were only found in Rhizobiales and Rhodospirillales of the α-Proteobacteria AidBAt from Agrobacterium and AidBRm from Rhizobium (amino acid identities of 50.6% and 52.8% to AidB, respectively) also showed thermostable AHL degradation activity. When introduced into bacteria, plasmid-expressed AidB attenuated pyocyanin production by Pseudomonas aeruginosa PAO1 and the pathogenicity of Pectobacterium carotovorum subsp. carotovorum Z3-3, suggesting that AidB is a potential therapeutic agent by degrading AHLs.IMPORTANCE Quorum-sensing system using AHLs as the signal in many bacterial pathogens is a critical virulence regulator and an attractive target for anti-infective drugs. In this work, we identified a novel AHL lactonase AidB from a soil bacterial strain Bosea sp. F3-2. The expression of aidB reduced the production of AHL signals and QS-dependent virulence factors in Pseudomonas aeruginosa and Pectobacterium carotovorum The homologs of AidB with AHL degrading activities were only found in several genera belong to α-Proteobacteria Remarkably, AidB is a thermostable enzyme retained its catalytic activity after treatment at 80°C for 30 min and exhibits reliable storage stability at both 4 °C and room temperature. These properties might make it more suitable for practical application.

5.
Yi Chuan ; 41(10): 919-927, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31624054

RESUMO

Fibrillin-2 (FBN2) is an important component of microfibers which are involved in the formation of elastic fibers in connective tissue throughout the human body. Hereditary connective tissue diseases may result from genetic mutations of FBN2 causing heterogeneity of fibrin. Genetic mutations of FBN2 are associated with a variety of hereditary connective tissue diseases including Congenital Contractural Arachnodactyl (CCA), Macular Degeneration (MD), and myopathy. Studies have shown that the FBN2 gene is recognized as the only pathogenic gene related to CCA and that CCA patients have different clinical presentations depending on the identified genetic mutations at different FBN2 sites. In this review, we summarize the roles of FBN2, its mutations and impact on the physiological and pathological processes of many hereditary connective tissue diseases. We include brief descriptions of clinical manifestations of these diseases providing a basis for further exploration of the specific molecular mechanism of FBN2 gene mutation pathogenesis which provides a theoretical basis for the therapy and medications for refractory diseases caused by FBN2 gene mutation.

6.
PLoS One ; 14(10): e0224153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31661503

RESUMO

Fairness concern behavior is extremely common in social life, and many scholars are beginning to pay attention to this behavior. In this study, we investigate a two-echelon construction supply chain that consists of a general contractor and a subcontractor under cap-and-trade policy. We study the carbon emission reduction decisions and profit distribution mechanism in the construction supply chain with fairness concern and cap-and-trade. We use the Nash bargaining model to describe the fairness concerns of the construction supply chain members and use the co-opetition model to portray the profit distribution. We show that the fairness concern can impose an adverse influence on firms' profits and decrease the magnitude of their carbon emission reductions. The subcontractor's fairness concern causes greater losses to the construction supply chain's profit. We further demonstrate the impact of fairness concern on the optimal decisions of the general contractor and the subcontractor through numerical analysis.

7.
J Matern Fetal Neonatal Med ; : 1-9, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31533498

RESUMO

Objectives: We conducted this study to investigate the risk factors for spontaneous abortion among rural Chinese women. Methods: Risk factors prior to pregnancy associated with spontaneous abortion were identified among 17,248 rural women enrolled in a prospective population-based follow-up study. The risk of spontaneous abortion was estimated with odds ratio (OR) and 95% confidence interval (CI) for several factors. A nonconditional logistic regression analysis was then performed to identify the independently associated factors. Results: The total sample of this study population consisted of 17,248 pregnant women including 921 of them whose pregnancies resulted in spontaneous abortion and the incidence of spontaneous abortion was 5.04%. After the adjustment of confounding factors, menarche age, serum creatinine, family genetic diseases or maternal congenital defects was associated with an increased risk of spontaneous abortion while folic acid supplementation reduced the risk among rural Chinese women. Conclusions: The findings of our study suggest that multiple modifiable factors may increase the risk of spontaneous abortion which may help relevant departments better to guide detailed effectively prevention strategies toward spontaneous abortion to improve the reproductive quality of rural population. Further studies are required to elaborate these risk factors for spontaneous abortion.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31512361

RESUMO

Understanding the effects of intermolecular interactions on metal-to-metal charge transfer (MMCT) is crucial to develop molecular devices by grafting MMCT-based molecular arrays. Herein, we report a series of solvent-free {Fe2 Co2 } compounds sharing the same cationic tetranuclear {[Fe(PzTp)(CN)3 ]2 [Co(dpq)2 ]2 }2+ (PzTp- =tetrakis(pyrazolyl)borate, dpq=dipyrido[3,2-d:2',3'-f]quinoxaline) square units but having anions with different size, including BF4 - , PF6 - , OTf- , and [Fe(PzTp)(CN)3 ]- . Intermolecular π⋅⋅⋅π interactions between dpq ligands, which coordinate to cobalt ions in the {[Fe(PzTp)(CN)3 ]2 [Co(dpq)2 ]2 }2+ units, can be modulated by introducing different counterions, regulating the distortion of the CoN6 octahedron and ligand field around the cobalt ions. This change results in different MMCT behavior. Computational analyzes reveal the substantial role of the intermolecular interactions tuned by the presence of different counteranions on the MMCT behavior.

9.
Theranostics ; 9(21): 6269-6283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534550

RESUMO

Sepsis is a major cause of patient mortality and morbidity from bacterial infections. Although neutrophils are known to be important in the development of sepsis, how distinctive neutrophil subtypes regulate inflammatory processes involved in septicemia remains unclear. Preconditioning protects organisms against subsequent higher-dose exposures to the same, or even different, stimuli. Several studies have reported various effects of preconditioning on immune cells. However, the detailed mechanisms underlying neutrophil-mediated protection through preconditioning in sepsis remain unknown. Methods: Flow cytometry was conducted to sort the mice peritoneal lavage cells and the blood samples from patients with sepsis. Western blotting and ELISA were carried out to elucidate the expression of TLR9 signal transduction pathway proteins. Histological analysis was used to assess the effect of InP on intestine and liver structure in tlr9-/- and cav-1-/- mice. Fluorescence microscopy, Co-IP, and FRET were carried out to determine the association of TLR9 with Cav-1. Results: We show that membrane toll-like receptor-9 positive (mTLR9+) neutrophils exert a protective effect against fatal bacterial infections through the process of inflammatory preconditioning (InP). InP, which occurs in the setting of a low-dose bacterial challenge, active ingredient is Monophosphoryl lipid A (MPLA), triggers the membrane translocation of TLR9 from the neutrophil cytosol, where it binds to Cav-1. Our findings showed that InP enables TLR9 to facilitate MyD88-mediated TRAF3 and IRF3 signal transduction. Depletion of either TLR9 or Cav-1 largely eliminates the neutrophil-mediated InP effect in sepsis models in vitro and in vivo. Further, examination of clinical samples from patients with sepsis showed that clinical outcomes and likelihood of recovery are closely correlated with mTLR9 and Cav-1 expression in circulating neutrophils. Conclusion: These results demonstrate that the TLR9-Cav-1 axis is a critical signaling pathway involved in the regulation of neutrophil-dependent MPLA mediated InP, and the presence of mTLR9+ neutrophils could be an attractive indicator of clinical outcomes in bacterial sepsis that could be further explored as a potential therapeutic target.

10.
Nat Commun ; 10(1): 4363, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554794

RESUMO

The LKB1/AMPK pathway plays a major role in cellular homeostasis and tumor suppression. Down-regulation of LKB1/AMPK occurs in several human cancers and has been implicated in metabolic diseases. However, the precise upstream regulation of LKB1-AMPK pathway is largely unknown. Here, we report that AMPK activation by LKB1 is regulated by tankyrases. Tankyrases interact with and ribosylate LKB1, promoting its K63-linked ubiquitination by an E3 ligase RNF146, which blocks LKB1/STRAD/MO25 complex formation and LKB1 activation. LKB1 activation by tankyrase inhibitors induces AMPK activation and suppresses tumorigenesis. Similarly, the tankyrase inhibitor G007-LK effectively regulates liver metabolism and glycemic control in diabetic mice in a LKB1-dependent manner. In patients with lung cancer, tankyrase levels negatively correlate with p-AMPK levels and poor survival. Taken together, these findings suggest that tankyrase and RNF146 are major up-stream regulators of LKB1-AMPK pathway and provide another focus for cancer and metabolic disease therapies.

11.
Adv Mater ; : e1904058, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31553099

RESUMO

Many inorganic nanoparticles are prepared and their behaviors in living systems are investigated. Yet, common electrolytes such as NaCl are left out of this campaign. The underlying assumption is that electrolyte nanoparticles will quickly dissolve in water and behave similarly as their constituent salts. Herein, this preconception is challenged. The study shows that NaCl nanoparticles (SCNPs) but not salts are highly toxic to cancer cells. This is because SCNPs enter cells through endocytosis, bypassing cell regulations on ion transport. When dissolved inside cancer cells, SCNPs cause a surge of osmolarity and rapid cell lysis. Interestingly, normal cells are much more resistant to the treatment due to their relatively low sodium levels. Unlike conventional chemotherapeutics, SCNPs cause immunogenic cell death or ICD. In vivo studies show that SCNPs not only kill cancer cells, but also boost an anticancer immunity. The discovery opens up a new perspective on nanoparticle-based therapeutics.

12.
J Cardiothorac Surg ; 14(1): 172, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547844

RESUMO

OBJECTIVE: This study aims to discuss the efficacy and safety of the application of thrombus aspiration catheters during emergency PCI operations for acute ST-elevation myocardial infarction (STEMI) patients with high thrombus load. METHODS: A total of 204 patients diagnosed with acute STEMI and high thrombus load in the Sixth Affiliated Hospital of Guangxi Medical University from July 1, 2016 to June 30, 2017 were selected for the present study. These patients were randomly divided into two groups: thrombus catheter aspiration group (group A, n = 101), and balloon dilatation group (group B, n = 103). The blood flow of the culprit coronary artery in the thrombolysis in myocardial infarction (TIMI) immediately after the emergency PCI operation in these two groups of patients was recorded. Then, an echocardiogram was performed to determine the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) after the operation, and data on major adverse cardiovascular events (MACE) during the 30 days of postoperative follow-up were collected. RESULTS: The comparative difference between these two groups of patients in terms of hypertension, smoking, diabetes, usage rate of GPIIb/IIIa receptor antagonist, time from hospitalization to balloon dilatation (D2B) and other basic clinical data was not statistically significant (P > 0.05). The postoperative TIMI flow grade of these two groups of patients improved, and the comparative difference between the data obtained from these two groups was statistically significant (P < 0.05). The comparative difference between these two groups in terms of LVEDD and LVEF at 7 days after the operation was not statistically significant (P > 0.05). There was a difference in the occurrence rate of MACE in these two groups of patients during the 30 days of postoperative follow-up, but the comparative difference between these two groups was not statistically significant (P = 0.335). CONCLUSION: The application of thrombus aspiration catheter during the emergency PCI operation of STEMI patients with high thrombus load can better improve the myocardial reperfusion. There is no basis for increasing the stroke occurrence risk. However, it obviously fails to improve the recent prognosis and more studies need to explore its effect on myocardial remodeling and major adverse cardiovascular events.

13.
J Reprod Dev ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31474647

RESUMO

L-carnitine (LC) is well known for its antioxidant activity. In this study, we explored the potential mechanistic effects of LC supplementation on aged bovine oocytes in vitro. We showed that in-vitro maturation could enhance the subsequent developmental capacity of aging oocytes, when supplemented with LC. After in vitro fertilization, the blastocyst formation rate in the aged oocytes post-LC treatment significantly increased compared to that in untreated aged oocytes (29.23 ± 2.20% vs. 20.90 ± 3.05%). Furthermore, after LC treatment, the level of intracellular reactive oxygen species in aged oocytes significantly decreased, and glutathione levels significantly increased, compared to those in untreated aged oocytes. Mitochondrial membrane potential, the percentage of early apoptotic oocytes, and caspase-3 activity were significantly reduced in LC-treated aged oocytes compared to those in untreated aged oocytes. Furthermore, during in vitro aging, the mRNA levels of the anti-apoptotic genes, Bcl-xl and survivin in LC-treated aged oocytes were significantly higher than those in untreated aged oocytes. Overall, these results indicate that at least in in vitro conditions, LC can prevent the aging of bovine oocytes and improve the developmental capacity of bovine embryo.

14.
Peptides ; 121: 170153, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499086

RESUMO

Oxytocin (OXT) that effects the nociception process is mainly synthesized and secreted in the hypothalamic supraoptic nucleus (SON). Although the periaqueductal gray (PAG) hardly synthesizes OXT, OXT in PAG also plays a role in pain regulation. The communication investigates whether OXT in the PAG comes from SON to influence pain modulation. RT-PCR was used to analyze OXT mRNA expression and radioimmunoassay to measure OXT concentration. The results showed that (1) pain stimulation enhanced OXT mRNA expression in the SON at 10 min (268.1 ±â€¯39.2%, p < 0.001) and 20 min (135.4±37.9%, p < 0.05) treatment and did not change in the PAG; (2) OXT level increase in SON perfusion liquid during pain stimulation [236.7±22.1% at 10 min (p < 0.001), 223.1±12.4% at 20 min (p<0.001), 56.1 ±â€¯15.7% at 30 min (p < 0.01) and 11.2±14.2% at 40 min] was earlier than that in PAG perfusion liquid [17.8±9.7% at 10 min, 375.6±35.1% at 20 min (p <  0.001), 123.2±17.7% at 30 min (p <  0.001) and 52.7±22.4% at 40 min (p < 0.05)]; (3) SON excitation (L-glutamate sodium microinjection) induced OXT level increase in PAG perfusion liquid in a dose-dependent manner; (4) the bilateral SON cauterization completely controlled and the right SON cauterization partly reversed the pain stimulation induced-OXT concentration increase in PAG perfusion liquid. The data suggested that OXT in PAG came from SON, which might influence the pain process.

15.
Nat Rev Cancer ; 19(10): 568-586, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31462760

RESUMO

Cancer immunotherapies targeting adaptive immune checkpoints have substantially improved patient outcomes across multiple metastatic and treatment-refractory cancer types. However, emerging studies have demonstrated that innate immune checkpoints, which interfere with the detection and clearance of malignant cells through phagocytosis and suppress innate immune sensing, also have a key role in tumour-mediated immune escape and might, therefore, be potential targets for cancer immunotherapy. Indeed, preclinical studies and early clinical data have established the promise of targeting phagocytosis checkpoints, such as the CD47-signal-regulatory protein α (SIRPα) axis, either alone or in combination with other cancer therapies. In this Review, we highlight the current understanding of how cancer cells evade the immune system by disrupting phagocytic clearance and the effect of phagocytosis checkpoint blockade on induction of antitumour immune responses. Given the role of innate immune cells in priming adaptive immune responses, an improved understanding of the tumour-intrinsic processes that inhibit essential immune surveillance processes, such as phagocytosis and innate immune sensing, could pave the way for the development of highly effective combination immunotherapy strategies that modulate both innate and adaptive antitumour immune responses.

17.
Am J Reprod Immunol ; 82(5): e13180, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31397035

RESUMO

PROBLEM: Systemic immuno-inflammatory response caused by maternal immune imbalance is central to the pathogenesis of preeclampsia (PE). We hypothesized that changes in the number of decidual mesenchymal stem cells (dMSCs) may be associated with maternal immune imbalance. We aimed to evaluate the expression of CXCL12/CXCR4 axis in patients with PE and its influence on the migration behavior of dMSCs, to further clarify the pathogenesis of PE. METHOD OF STUDY: Fourteen women with PE and 11 controls were included. DMSCs were extracted from decidual tissue by type II collagenase digestion and adherence. ELISA and immunohistochemistry analysis were used to measure serum and tissue levels of CXCL12. Q-PCR and Western blotting were used to detect CXCR4 expression on dMSCs, whereas transwell assay was used to measure the migration ability of dMSCs. RESULTS: Decidual mesenchymal stem cells from women with PE showed higher expressions of CXCR4 and HIF-1α than the dMSCs of controls did. Tissues from women with PE showed the highest CXCL12 levels in the decidua, followed by the placenta and umbilical cord, whereas tissues from controls showed the highest CXCL2 levels in the umbilical cord, followed by the placenta and decidua. dMSCs from women with PE showed possibly higher migration ability than that of dMSCs from controls, under the induction of CXCL12, whereas dMSCs showed a decreasing trend in hypoxic than in normoxic environment. CONCLUSION: Decidual mesenchymal stem cells from women with PE can migrate to the decidua layer with the concentration gradient of CXCL12, which may play a role in the occurrence and development of PE.

18.
J Proteomics ; 208: 103478, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31394311

RESUMO

Asthenozoospermia, in which sperm motility is affected, is one of the primary causes of male infertility. However, the exact mechanism responsible for the defective motility remains unknown. It is important to identify the precise proteins or pathways involved in sperm motility. The present study analyzed five asthenozoospermic sperm samples and five healthy controls using TMT-based quantitative method and identified 152 differentially expressed proteins, with 84 upregulated and 68 downregulated in asthenozoospermia. Four proteins (GPI, MDH1, PGAM1 and PGAM2) were found in several over-represented energy metabolism pathways using bioinformatics analysis. Glucose-6-phosphate isomerase (GPI), a rate-limiting enzyme converting glucose-6-phosphate to fructose-6-phosphate, was found to be significantly decreased in asthenozoospermia by Western blotting and ELISA on an extended sample size. Furthermore, substitution of glucose with fructose-6-phosphate significantly promoted asthenozoospermic sperm motility in vitro. Taken together, our results suggest that the poor motility of sperm in asthenozoospermia may partly result from defects in GPI-associated energy metabolism. SIGNIFICANCE: To identify the key proteins or pathways involved in sperm motility, the accurate TMT-based quantitative method was applied to characterize protein profiles of asthenozoospermic sperm. GPI, an enzyme involved in energy metabolism, was found to be differentially abundant, and validated by extended sample analysis. The supplement of the product of GPI, fructose-6-phosphate, could significantly improve sperm motility. Our study could provide new insights into the molecular basis of sperm motility and the improvement of motility in asthenozoospermia.

19.
Anal Chem ; 91(16): 10901-10907, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31362489

RESUMO

Azoreductase (AzoR) is an essential reductive enzyme which is closely associated with the intestinal disease such as ulcerative colitis (UC). To date, only a few fluorescent probes for detecting AzoR activity in bacteria or cells have been constructed successfully. It is still challenging to design fluorescent probes for in situ monitoring AzoR in vivo. In this paper, a near-infrared (NIR) fluorescent probe (Cy-Azo) based on hemicyanine is designed and synthesized. The emission of the probe is located at 735 nm in the NIR region, which is favorable for its application in vivo. In addition, Cy-Azo shows high sensitivity to AzoR activity with 17-fold fluorescence enhancement and is particularly selective to AzoR over other enzymes, ions, and amino acids. Meanwhile, a possible response mechanism (the azo group in Cy-Azo is reduced by AzoR and cleaved resulting in the production of Cy-NH2) was proposed and verified by HPLC, MS, and theory calculation. In addition, based on low cell cytotoxicity, Cy-Azo is successfully applied in visualizing the activity of AzoR in two cell lines (HCT116 and HepG2 cells) and three types of bacteria (E. coli, S. aureus, and P. aeruginosa). In particular, due to its NIR emission, the probe can monitor AzoR activity in acute and chronic UC mice models. To our knowledge this is the first fluorescent probe for detecting AzoR activity in vivo, which can provide much important information for the diagnosis and treatment of UC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA