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1.
Talanta ; 236: 122835, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635225

RESUMO

Enrofloxacin (ENR) is a broad-spectrum fungicide that has been largely applied in pharmacy and animal-specific medicine. In this paper, a simple, novel and highly sensitive molecularly imprinted electrochemiluminescence (MIP-ECL) sensor based on mercaptopropionic acid-functionalized copper nanoclusters (MPA-Cu NCs) was developed to selectively detect enrofloxacin (ENR). MPA-Cu NCs prepared by a one-step method were used to modify the glassy carbon electrode. A molecularly imprinted polymer film containing the cavity was constructed after electropolymerization and elution. Under optimized conditions, the MIP-ECL sensor could detect ENR in the range of 0.1 nM-1 µM (R2 = 0.9863) with a low limit of detection of 27 pM, and the recovery rates of ENR in biological and lake water samples were 88.20-105.0%. The MIP-ECL sensor provided path to improve the stability issues of Cu NCs, which might open promising avenues to develop new ECL systems for biological analysis and environmental water monitoring.


Assuntos
Técnicas Biossensoriais , Impressão Molecular , Cobre , Eletrodos , Enrofloxacina
2.
PeerJ ; 9: e12162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721957

RESUMO

Background: To date, there have been no reports on the sexual and psychological health of patients with azoospermia during the coronavirus disease 2019 (COVID-19) pandemic. Previous studies on the sexual health of couples with azoospermia are limited and are especially lacking in data on the wives of azoospermic men. Methods: We conducted a case-control cross-sectional study between 1 July 2020 and 20 December 2020. In total, 100 couples with azoospermia comprised the experimental group and 100 couples with normozoospermia comprised the control group. The couples' sexual health was measured using standardised sexual function questionnaires (male: International Index of Erectile Function-15 [IIEF-15] and Premature Ejaculation Diagnostic Tool [PEDT]; female: Female Sexual Function Index [FSFI]) and a self-designed questionnaire to evaluate changes in sexual behaviours (sexual satisfaction, desire, frequency of sexual activity, masturbation, and pornography use) during lockdown. The couples' psychological health was measured using the 7-item Generalized Anxiety Disorder (GAD-7) scale and 9-item Patient Health Questionnaire (PHQ-9). The Actor-Partner Interdependence Model (APIM) was used to analyse the associations between sexual health and psychological health. Results: The IIEF-15 scores (53.07 ± 11.11 vs. 57.52 ± 8.57, t =  - 3.17, p = 0.00) were lower and the PEDT scores (6.58 ± 3.13 vs. 5.17 ± 2.22, t = 3.67, p = 0.00) and incidence of premature ejaculation (χ 2 = 14.73, p = 0.00) were higher for men with azoospermia than for men with normozoospermia. Compared with those of wives of men with normozoospermia, the total FSFI scores (25.12 ± 5.56 vs. 26.75 ± 4.82, t =  - 2.22, p = 0.03) of wives of men with azoospermia were lower. The chi-square test showed that the perceived changes in sexual satisfaction (χ 2 = 7.22, p = 0.03), frequency of masturbation (χ 2 = 21.96, p = 0.00), and pornography use (χ 2 = 10.90, p = 0.01) were significantly different between the female groups with azoospermia and normozoospermia, but there were no significant changes in sexual behaviour between the male groups. The GAD-7 (men: 7.18 ± 5.56 vs. 5.68 ± 4.58, p = 0.04; women: 6.65 ± 5.06 vs. 5.10 ± 3.29, p = 0.01) and PHQ-9 scores (men: 10.21 ± 6.37 vs. 7.49 ± 6.10, p = 0.00; women: 8.81 ± 6.50 vs. 6.98 ± 4.43, p = 0.02) were significantly higher for couples with azoospermia than for couples with normozoospermia. The APIM showed that for couples with azoospermia, sexual function negatively correlated with their own anxiety (men: ß = -0.22, p = 0.00; women: ß = -0.38, p = 0.00) and depression symptoms (men: ß = -0.21, p = 0.00; women: ß = -0.57, p = 0.00) but not with their partner's anxiety and depression symptoms (p > 0.05). Conclusions: Couples with azoospermia had a lower quality of sexual function and higher levels of psychological distress than couples with normozoospermia. Their sexual health negatively correlated with psychological distress.

3.
Appl Opt ; 60(31): 10002-10008, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34807195

RESUMO

Large-scale optical fiber phased arrays (OFPAs) are capable of realizing high-power lasers and high-speed beam steering, which are widely used in long-distance detection and communication. However, dephasing occurring from optical fiber jitter and power amplifier noise can reduce beam quality and steering precision in applications. We demonstrate a two-dimensional 64-element OFPA system that employs a stochastic parallel gradient descent algorithm to synchronize the phases and thus achieve high-quality multi-beam output. Using multi-beam steering, the total scan time for covering a certain field of view can be shorter compared to single-beam steering. Moreover, an avalanche photodiode array is used to enhance the precision of the voltage for beam steering. Experimental results show that the peak sidelobe ratio of the main beam achieves 23.7 dB, and the speed of the beam steering between two discretionary angles is 128 kHz.

4.
Transl Androl Urol ; 10(10): 3862-3872, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804828

RESUMO

Background: Varicocele (VC) is one of the most common causes of infertility in men, and microscopic varicocelectomy is currently the major surgical procedure for VC. We assessed the clinical effectiveness of microsurgical subinguinal varicocelectomy (MSV) with enhanced recovery after surgery (ERAS) in the treatment of VC in terms of semen quality improvement rate, pregnancy rate, pain relief rate, recurrence rate, and complication rate after MSV and explored the indications for VC surgery. Methods: In total, 216 patients undergoing MSV in our center between June 2019 and July 2020 were enrolled in this study. All patients received the surgery under local anesthesia and were admitted and discharged within 24 hours. All patients were followed up for more than 6 months, and the rates of semen quality improvement, pregnancy, pain relief, recurrence, and postoperative complications were recorded. We can evaluate the pain degree of patients through the numerical rating scale (NRS). (I) 0 points for painless; (II) 1-3: mild pain; (III) 4-6: moderate pain; (IV) 7-10 points are severe pain. 0 is the most slightly, indicating comfort, and 10 is the most painful and unbearable. Results: The sperm concentration, total sperm count, progressive motility rate, sperm viability, and morphology were significantly improved after the surgery (all P values <0.05). The rate of semen quality improvement was 88.2%, and the semen indicators returned to normal in 26.6% of the patients. Among the patients who were followed up for 1 year, the natural conception rate reached 27.1% and was accompanied by a 95.5% pain relief rate, a 0.5% VC recurrence rate, and a 2.3% postoperative complication rate.We obtained data through laboratory examination of semen DNA fragments index (DFI). Compared with preoperative and postoperative DFI, postoperative DFI was improved, and the pregnancy outcome was improved. Conclusions: MSV under local anesthesia increases the rates of semen quality improvement, pregnancy, and pain relief while lowering the rates of recurrence and postoperative complications. MSV may also help to improve the pregnancy outcomes in patients with VC accompanied by sperm DNA fragmentation or nonobstructive azoospermia, but this should be verified by further investigation.

5.
Oncogene ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782718

RESUMO

Bladder cancer (BLCA) is the most common malignant tumor of the urinary system and is characterized by high metastatic rates and poor prognosis. The expression of tight junction protein 1 (TJP1) is associated with bladder cancer invasion; however, the mechanism by which TJP1 affects vasculature remodeling remains unknown. In this study, we found that TJP1 expression correlated with tumor angiogenesis and poor overall survival in clinical samples. Furthermore, TJP1 overexpression promoted tumor angiogenesis in BLCA cells and stimulated recruitment of macrophages to tumors by upregulating CCL2 expression. Mechanistically, TJP1 interacted with TWIST1 and enhanced the transcriptional activity of CCL2. The impairment of tumor angiogenesis caused by knockdown of TJP1 was dramatically rescued by overexpression of TWIST1. Furthermore, TJP1 recruited USP2, which deubiquitinated TWIST1, thereby protecting TWIST1 from proteasome-mediated protein degradation. In conclusion, our results suggest that TJP1 controls angiogenesis in BLCA via TWIST1-dependent regulation of CCL2. We demonstrate that TJP1 functions as a scaffold for the interaction between USP2 and TWIST1 and this may provide potential therapeutic targets in bladder cancer.

6.
J Hum Hypertens ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782738

RESUMO

Little information is available on the association between brachial-ankle pulse wave velocity (baPWV) and the risk of stroke in Chinese H-type hypertension patients. Therefore, our study aimed to assess this association between baseline baPWV and short-term risk of first stroke and to propose a cutoff value of baPWV that could predict near cerebrovascular events. A total of 9787 hypertension patients without preexisting stroke who underwent baPWV measurement were included. The primary end points were first symptomatic stroke. Secondary end points were first ischemic stroke and first hemorrhagic stroke. During a median follow-up of 20.8 months, there was a total of 138 first strokes including 123 first ischemic strokes and 15 first hemorrhagic strokes. When baPWV was categorized in quartiles, the higher risks of first stroke (HR = 1.52; 95% CI: 1.05-2.21) and first ischemic stroke (HR = 1.53; 95% CI: 1.03-2.26) were found in participants in quartile 4 (≥21.31 m/s), compared with those in quartile 1-3 (<21.31 m/s). In receiver operating characteristic curve analysis, the best cutoff value of baPWV that could predict first stroke was 21.43 m/s. Higher baPWV (≥21.43 m/s) was significantly associated with increased risk of first stroke (HR = 1.60; 95% CI: 1.10-2.32) and first ischemic stroke (HR = 1.60; 95% CI: 1.08-2.37). In conclusion, higher baPWV levels were associated with an increased risk of first stroke among Chinese H-type hypertensive patients. In addition, a cutoff value of 21.43 m/s of baPWV was proposed that could predict the next two years' cerebrovascular events.

7.
Lipids Health Dis ; 20(1): 160, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774030

RESUMO

BACKGROUND: The high drug resistance and metabolic reprogramming of clear cell renal cell carcinoma (ccRCC) are considered responsible for poor prognosis. In-depth research at multiple levels is urgently warranted to illustrate the lipid composition, distribution, and metabolic pathways of clinical ccRCC specimens. METHODS: In this project, a leading-edge targeted quantitative lipidomic study was conducted using 10 pairs of cancerous and adjacent normal tissues obtained from ccRCC patients. Accurate lipid quantification was performed according to a linear equation calculated using internal standards. Qualitative and quantitative analyses of lipids were performed with multiple reaction monitoring analysis based on ultra-performance liquid chromatography (UPLC) and mass spectrometry (MS). Additionally, a multivariate statistical analysis was performed using data obtained on lipids. RESULTS: A total of 28 lipid classes were identified. Among them, the most abundant were triacylglycerol (TG), diacylglycerol (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Cholesteryl ester (CE) was the lipid exhibiting the most considerable difference between normal samples and tumor samples. Lipid content, chain length, and chain unsaturation of acylcarnitine (CAR), CE, and DG were found to be significantly increased. Based on screening for variable importance in projection scores ≥1, as well as fold change limits between 0.5 and 2, 160 differentially expressed lipids were identified. CE was found to be the most significantly upregulated lipid, while TG was observed to be the most significantly downregulated lipid. CONCLUSION: Based on the absolute quantitative analysis of lipids in ccRCC specimens, it was observed that the content and change trends varied in different lipid classes. Upregulation of CAR, CE, and DG was observed, and analysis of changes in the distribution helped clarify the causes of lipid accumulation in ccRCC and possible carcinogenic molecular mechanisms. The results and methods described herein provide a comprehensive analysis of ccRCC lipid metabolism and lay a theoretical foundation for cancer treatment.

8.
Am J Cancer Res ; 11(10): 5076-5093, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765313

RESUMO

Hypoxia is a common feature of tumor microenvironment (TME). This study aims to establish the genetic features related to hypoxia in Bladder urothelial carcinoma (BLCA) and investigate the potential correlation with hypoxia in the TME and immune cells. We established a BLCA outcome model using the hypoxia-related genes from The Cancer Genome Atlas using regression analysis and verified the model using the Gene Expression Omnibus GSE32894 cohort. We measured the effect of each gene in the hypoxia-related risk model using the Human Protein Atlas website. The predictive abilities were compared using the area under the receiver operating characteristic curves. Gene Set Enrichment Analysis was utilized for indicating enrichment pathways. We analyzed immune cell infiltration between risk groups using the CIBERSORT method. The indicators related to immune status between the two groups were also analyzed. The findings indicated that the high-risk group had better outcomes than the low-risk group in the training and validation sets. Each gene in the model affected the survival of BLCA patients. Our hypoxia-related risk model had better performance compared to other hypoxia-related markers (HIF-1α and GLUT-1). The high-risk group was enriched in immune-related pathways. The expression of chemokines and immune cell markers differed significantly between risk groups. Immune checkpoints were more highly expressed in the high-risk group. These findings suggest that the hypoxia-related risk model predicts patients' outcomes and immune status in BLCA risk groups. Our findings may contribute to the treatment of BLCA.

9.
Front Nutr ; 8: 714291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746202

RESUMO

Background: Evidence of an association between dairy product and main related dairy nutrient intake, and the asthenozoospermia risk have been limited and controversial. Methods: A hospital-based case-control study including 549 men with asthenozoospermia and 581 normozoospermic controls was carried out in the infertility clinics of Shengjing Hospital of China Medical University between June, 2020 and December, 2020. Dietary intake was assessed with a validated food frequency questionnaire. According to the World Health Organization guidelines, semen parameters were collected through masturbation and were measured with WLJY9000 instrument and flow cytometry. The daily intake of dairy products and related nutrients was categorized into three groups according to control distribution, and the lowest tertile was used as the reference category. An unconditional multiple logistic regression was used to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for asthenozoospermia risk. Results: After adjustment for potential confounders, we found no statistically significant associations between the intake of total dairy products and asthenozoospermia risk (ORT3vs.T1 = 1.19, 95%CI = 0.85-1.67). Additionally, we generated null findings regarding the main related nutrients from dairy, including protein (ORT3vs.T1 = 1.19, 95%CI = 0.85-1.68), fat (ORT3vs.T1 = 1.28, 95%CI = 0.91-1.80), calcium (ORT3vs.T1 = 1.20, 95%CI = 0.85-1.68), saturated fatty acids (ORT3vs.T1 = 1.30, 95%CI = 0.92-1.83), and phosphorous (ORT3vs.T1 = 1.18, 95%CI = 0.84-1.67), and the asthenozoospermia risk. Of note, after stratification by body mass index (BMI), and the saturated fatty acids consumption from dairy was significantly associated with a higher asthenozoospermia risk (ORT3vs.T1 = 1.76, 95%CI = 1.01-3.09) among participants with a BMI below 25 kg/m2. Conclusion: This study provided limited evidence of an association between the intake of total dairy products and the main related dairy nutrients including protein, fat, calcium, saturated fatty acids, and phosphorus, and the asthenozoospermia risk. Further studies are warranted to confirm our findings in the future.

10.
J Exp Bot ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34752617

RESUMO

Winter dormancy (WD) is the most crucial strategy for plants coping with potentially deadly environments. In recent decades, this process in economically important perennial eudicots has been extensively studied due to changing climates. However, in evergreen monocots with no chilling requirements, dormancy processes are so far a mystery. In this study, we compared the WD process in closely related evergreen (Iris japonica) and deciduous (I. tectorum) iris species across crucial developmental time points. Both iris species exhibit a "temporary" WD process with distinct durations, and could easily resume growth under warm conditions. To decipher transcriptional changes, full-length sequencing for evergreen iris, while short read RNA-sequencing for deciduous one was applied to generate respective reference transcriptome. Combining results from the multipronged approach, SHORT VEGETATIVE PHASE and FRUITFULL (FUL) from MADS-box was associated with dormancy- and growth-related module, respectively. They were coexpressed with genes involved in phytohormone signaling, carbohydrate metabolism, and environmental adaptation. Also, gene expression patterns and physiological changes in above pathways highlighted potential abscisic acid and jasmonic acid antagonism in coordinating growth and stress responses, whereas differences in carbohydrate metabolism and reactive oxygen species scavenging might lead to species-specific WD durations. Moreover, a detailed analysis of MIKC C  MADS-box in irises revealed common features described in eudicots as well as possible new roles for members in monocots during temporary WD, such as FLOWERING LOCUS C and FUL. In essence, our results not only provide a portrait of temporary WD in perennial monocots but also offer new insights into the regulatory mechanism underlying WD in plants.

11.
Brain Sci ; 11(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34679367

RESUMO

Oxidative stress mechanisms may explain associations between perinatal acetaminophen exposure and childhood attention-deficit hyperactivity disorder (ADHD). We investigated whether the changes in umbilical cord plasma amino acids needed to synthesize the antioxidant glutathione and in the oxidative stress biomarker 8-hydroxy-deoxyguanosine may explain the association between cord plasma acetaminophen and ADHD in the Boston Birth Cohort (BBC). Mother-child dyads were followed at the Boston Medical Center between 1998 and 2018. Cord plasma analytes were measured from archived samples collected at birth. Physician diagnoses of childhood ADHD were obtained from medical records. The final sample consisted of 568 participants (child mean age [SD]: 9.3 [3.5] years, 315 (52.8%) male, 248 (43.7%) ADHD, 320 (56.3%) neurotypical development). Cord unmetabolized acetaminophen was positively correlated with methionine (R = 0.33, p < 0.001), serine (R = 0.30, p < 0.001), glycine (R = 0.34, p < 0.001), and glutamate (R = 0.16, p < 0.001). Children with cord acetaminophen levels >50th percentile appeared to have higher risk of ADHD for each increase in cord 8-hydroxy-deoxyguanosine level. Adjusting for covariates, increasing cord methionine, glycine, serine, and 8-hydroxy-deoxyguanosine were associated with significantly higher odds for childhood ADHD. Cord methionine statistically mediated 22.1% (natural indirect effect logOR = 0.167, SE = 0.071, p = 0.019) and glycine mediated 22.0% (natural indirect effect logOR = 0.166, SE = 0.078, p = 0.032) of the association between cord acetaminophen >50th percentile with ADHD. Our findings provide some clues, but additional investigation into oxidative stress pathways and the association of acetaminophen exposure and childhood ADHD is warranted.

12.
Psychosom Med ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34654026

RESUMO

OBJECTIVE: We aimed to investigate the prospective association between self-perceived psychological stress and first stroke, and examine possible effect modifiers among adults with hypertension. METHODS: A total of 20,688 hypertensive adults with information on self-perceived psychological stress at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). Participants were randomly assigned to a double-blind treatment of receiving a single tablet daily with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. Follow up visits occurred every 3 months after randomization. Psychological stress was measured with a one-item 3-point rating scale. The primary outcome was first stroke (fatal or nonfatal). RESULTS: The median treatment period was 4.5 years. Compared with participants with low levels of psychological stress, those with high psychological stress had a significantly higher risk of first stroke (adjusted HR, 1.40; 95%CI: 1.01, 1.94) or first ischemic stroke (adjusted HR, 1.45; 95%CI: 1.01, 2.09). Moreover, a stronger positive relationship between psychological stress and first stroke was found in participants with time-averaged mean arterial pressure (MAP) <101 mmHg (median) (P-interaction = 0.004) during the treatment period. However, our study did not find a significant association between psychological stress and first hemorrhagic stroke. CONCLUSIONS: Higher psychological stress was associated with an increased risk of first stroke among treated hypertensive patients, especially in those with lower MAP during the treatment period.

13.
Pediatr Pulmonol ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607393

RESUMO

BACKGROUND: Previous studies on maternal folate status during pregnancy and child asthma risk yielded mixed results, and few considered maternal asthma history, a known risk factor of childhood asthma. This study examined whether the role of maternal folate in childhood asthma differs by maternal asthma history and whether there is an interaction between the two factors. METHODS: This study included 1948 mother-child dyads from the Boston Birth Cohort. Childhood asthma was defined based on physician diagnosis documented in electronic medical records, and maternal asthma was based on standard questionnaire interview. Maternal plasma folate level within a few days of delivery was measured by chemiluminescent immunoassay. Logistic regression models were applied to examine individual and joint associations of maternal asthma history and plasma folate level with childhood asthma, adjusting for other covariables. RESULTS: When stratified by maternal asthma history, an L-shaped relationship between maternal folate level and child asthma was observed in children born to mothers with asthma history (pinteraction = 0.03). The highest risk was found in children having maternal asthma history and low maternal folate level (odds ratio = 5.93; 95% confidence interval: 2.86-12.3) compared with children without maternal asthma history and with sufficient maternal folate levels. Sensitivity analyses using different definitions of asthma and stratified by major covariables yielded similar findings. CONCLUSION: In this US prospective high-risk birth cohort, maternal asthma history and low folate level interactively increased the risk of child asthma. If further confirmed, optimizing maternal folate levels during pregnancy may mitigate child asthma risk in the setting of maternal asthma history.

14.
Allergy Asthma Clin Immunol ; 17(1): 102, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627374

RESUMO

BACKGROUND: Knowledge is limited about the relationship between clinical reactivity to foods through breastfeeding and long-term food allergy outcomes. We explored parent-perceived symptoms of food allergy via breastfeeding and the association with future tolerance. METHODS: Subjects identified from the Chicago Food Allergy Study (2005-2011) were categorized by parent-reported reactions to maternally ingested foods via breastfeeding (50/898 peanut-allergic, 69/620 egg-allergic, and 153/589 milk-allergic). The primary outcome was tolerance [passed oral food challenge (OFC) or consumption of previously implicated food]. Secondary outcomes included severe reactions (anaphylaxis and/or cardiovascular/respiratory symptoms) and additional concomitant food allergies. Univariate chi-square analyses were performed to assess for association between variables, followed by logistic regression models. RESULTS: Of the 50 subjects with parent-reported peanut-associated symptoms with breastfeeding, none gained tolerance. There were no significant associations between parent-reported breastfeeding symptoms and development of tolerance for egg and milk (egg: OR 0.46, 95% CI 0.21-1.01, p = 0.053; milk: OR 1.13, 95% CI 0.70-1.81, p = 0.614). All egg-allergic subjects with parent-perceived symptoms while breastfeeding also reported multiple food allergies (n = 69), but milk- and peanut-allergic subjects were not more likely to have multiple allergies (milk: OR 1.89, 95% CI 0.88-4.02, p = 0.10; peanut: OR 2.36, 95% CI 0.72-7.76, p = 0.16). There were no significant associations between parent-reported breastfeeding symptoms and subsequent reaction severity. CONCLUSIONS: A significant proportion of parents perceive symptoms of food allergy attributable to indirect breastfeeding exposures. Our exploratory analysis suggests that infants with parent-perceived clinical reactivity to peanut via breastmilk may be less likely to gain tolerance. Infants with parent-reported reactivity to egg via breastmilk exposure were more likely to report multiple food allergies. Further rigorous prospective studies are needed to clarify the true prevalence of IgE-mediated food allergy symptoms attributable to indirect breastfeeding exposures and the association with development of tolerance.

15.
J Cell Mol Med ; 25(21): 10164-10174, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34651428

RESUMO

Mantle cell lymphoma (MCL) is a haematologic malignancy. The proteasome inhibitor (PI) bortezomib has been approved to treat MCL, but resistance has emerged through mechanisms that remain unclear. This study aimed to explore the mechanism of PI resistance in MCL and identify new targets for this patient subgroup. Carfilzomib-resistant (CR) MCL cell lines and primary samples were used for both in vitro and in vivo experiments to identify gene expression and explore their related signalling pathways. We first identified mucin 20 (MUC20) suppression in carfilzomib-resistant MCL models. MUC20 overexpression sensitized cells to carfilzomib in vitro and in vivo. MUC20 expression was inversely related to activation of c-Met and the downstream p44/42 MAPK pathway. c-Met activation with hepatocyte growth factor (HGF) induced PI resistance, while c-Met inhibition restored PI sensitivity. Carfilzomib resistance and depressed MUC20 expression were associated with enhanced proteasome activity and higher expression of proteassemblin (POMP), a chaperone for catalytically active proteasome assembly. c-Met and POMP were associated through binding and induction of MAPK-regulated ELK1 to the POMP promoter. Our data reveal that c-Met signalling activation enhanced proteasome capacity as a mechanism of PI resistance, and MUC20 expression may be a useful biomarker for PI therapy.

16.
Proc Natl Acad Sci U S A ; 118(38)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34521752

RESUMO

CtIP is a DNA end resection factor widely implicated in alternative end-joining (A-EJ)-mediated translocations in cell-based reporter systems. To address the physiological role of CtIP, an essential gene, in translocation-mediated lymphomagenesis, we introduced the T855A mutation at murine CtIP to nonhomologous end-joining and Tp53 double-deficient mice that routinely succumbed to lymphomas carrying A-EJ-mediated IgH-Myc translocations. T855 of CtIP is phosphorylated by ATM or ATR kinases upon DNA damage to promote end resection. Here, we reported that the T855A mutation of CtIP compromised the neonatal development of Xrcc4 -/- Tp53 -/- mice and the IgH-Myc translocation-driven lymphomagenesis in DNA-PKcs -/- Tp53 -/- mice. Mechanistically, the T855A mutation limits DNA end resection length without affecting hairpin opening, translocation frequency, or fork stability. Meanwhile, after radiation, CtIP-T855A mutant cells showed a consistent decreased Chk1 phosphorylation and defects in the G2/M cell cycle checkpoint. Consistent with the role of T855A mutation in lymphomagenesis beyond translocation, the CtIP-T855A mutation also delays splenomegaly in λ-Myc mice. Collectively, our study revealed a role of CtIP-T855 phosphorylation in lymphomagenesis beyond A-EJ-mediated chromosomal translocation.

17.
Autism Res ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558795

RESUMO

Selenium (Se) is an essential trace element involved in various biological processes, including neurodevelopment. Available literature indicates that both Se deficiency and excess may be detrimental to health. It is also known that Se can cross the placenta from maternal to fetal circulation. To date, the role of maternal Se status in child long-term neurodevelopment is largely unexplored. This study investigated the temporal and dose-response associations between maternal Se status and child risk of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). It consisted of 1550 mother-infant dyads from the Boston Birth Cohort. Maternal red blood cell (RBC) Se levels were measured in samples collected within 72 h of delivery (biomarker of third trimester Se status). Pediatric neurodevelopmental diagnoses were obtained from electronic medical records. Data analyses showed that maternal RBC Se levels were positively associated with child risk of developing ASD, with an adjusted odds ratio of 1.49 for ASD (95% CI: 1.09, 2.02) per IQR increase in Se. There was also a positive association between maternal Se and ADHD (OR: 1.29; 95% CI: 1.04, 1.56, per IQR increase in Se). These associations remained robust even after adjusting for pertinent covariables; and there was no significant interaction between Se and these covariables. Our findings suggest that prenatal exposure to high maternal Se levels may adversely affect child neurodevelopment. Our findings warrant further investigation; if confirmed, optimizing maternal prenatal Se levels may be necessary to maximize its health benefits while preventing undue risk.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34474950

RESUMO

In this E-Challenge, the authors report on a patient with symptoms of exertional dyspnea and angina, scheduled to have surgical unroofing of an identified myocardial bridge (MB). An MB is very common in patients with hypertrophic cardiomyopathy (HCM). Intraoperative transesophageal echocardiography with provocative maneuvers revealed the patient had a systolic anterior motion of the mitral valve with septal contact and resulting outflow tract obstruction despite the notable absence of significant basal septal hypertrophy. HCM has many phenotypic variants that can make the identification of patients with latent left ventricular outflow tract obstruction difficult in the absence of a high index of suspicion. In this report, the authors discuss the association between MBs and HCM and the importance of recognizing phenotypic variants of HCM.

19.
Sci Rep ; 11(1): 18181, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518608

RESUMO

To investigate the effects of ketamine on glucose uptake and glucose transporter (GLUT) expression in depressive-like mice. After HA1800 cells were treated with ketamine, 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) was added to the cells to test the effects of ketamine on glucose uptake, production of lactate, and expression levels of GLUT, ERK1/2, AKT, and AMPK. Adult female C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS), 27 CUMS mice were randomly divided into the depression, ketamine (i.p.10 mg/kg), and FR180204 (ERK1/2 inhibitor, i.p.100 mg/kg) + ketamine group. Three mice randomly selected from each group were injected with 18F-FDG at 6 h after treatment. The brain tissue was collected at 6 h after treatment for p-ERK1/2 and GLUTs. Treatment with ketamine significantly increased glucose uptake, extracellular lactic-acid content, expression levels of GLUT3 and p-ERK in astrocytes and glucose uptake in the prefrontal cortex (P < 0.05), and the immobility time was significantly shortened in depressive-like mice (P < 0.01). An ERK1/2 inhibitor significantly inhibited ketamine-induced increases in the glucose uptake in depressive-like mice (P < 0.05), as well as prolonged the immobility time (P < 0.01). The expression levels of p-ERK1/2 and GLUT3 in depressive-like mice were significantly lower than those in normal control mice (P < 0.01). Ketamine treatment in depressive-like mice significantly increased the expression levels of p-ERK1/2 and GLUT3 in the prefrontal cortex (P < 0.01), whereas an ERK1/2 inhibitor significantly inhibited ketamine-induced increases (P < 0.01).Our present findings demonstrate that ketamine mitigated depressive-like behaviors in female mice by activating the ERK/GLUT3 signal pathway, which further increased glucose uptake in the prefrontal cortex.

20.
J Nutr ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558624

RESUMO

BACKGROUND: Associations between vitamin D and stroke remain inconsistent. One major risk factor for stroke is high blood glucose, but the role it plays in this association is not well-studied. OBJECTIVES: We aimed to evaluate the individual association between plasma 25-hydroxyvitamin D (25(OH)D) and risk of first stroke stratified by fasting blood glucose (FBG), and the joint associations between plasma 25(OH)D, glycemic status and first stroke in hypertensive adults. METHODS: This study was a nested, case-control design utilizing data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 591 first stroke cases (of which 475 were ischemic stroke, 114 were hemorrhagic stroke, and 2 were uncertain type) and 591 matched controls. The age range of the study population was 45-75 years. The normal FBG (NFG) group had FBG < 5.6 mmol/L,  and the impaired FBG (IFG) group had FBG ≥ 5.6 mmol/L and < 7.0 mmol/L. Diabetes was defined as participants with FBG ≥ 7 mmol/L or who were receiving treatment with hypoglycemic agents. Odds ratios (ORs) (95% confidence intervals) were calculated using unconditional logistic regression models. RESULTS: Multivariable adjusted models revealed an inverse association between quartiles of 25(OH) D and risk of first stroke among participants with NFG, but the opposite trend was observed for those with IFG or diabetes. The largest odds ratios (>2) were observed among patients with diabetes, compared to the reference group of NFG and high 25(OH)D. Those with NFG and low 25(OH)D (OR = 1.73, 95%CI = 1.22 to 2.44) or those with IFG and high 25(OH)D (OR = 1.74, 95%CI = 1.14 to 2.67) both had higher risk of total stroke. There was a significant interaction between 25(OH)D and a combined group of IFG and diabetes (P = 0.001). Similar results were observed for ischemic stroke. CONCLUSIONS: In a hypertensive population, the relation between plasma 25(OH)D and risk of first stroke was significantly modified by fasting blood glucose.Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.

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