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1.
Anal Bioanal Chem ; 413(26): 6639-6647, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34595556

RESUMO

Herein, a novel, convenient, and highly selective electrochemical sensor for determination of nitrite based on a polythiophene-derivative film-modified glassy carbon electrode (GCE) was established. In this work, 2,5-di-thiophen-3-yl-thiazolo[5,4-d]thiazole (DTT), a novel thiophene derivative, was synthesized and used to form an original and excellent polymer film (PolyDTTF) on GCE through one-step electropolymerization for the first time. The modified electrodes were characterized by electron microscopy (SEM), Fourier transform infra-red spectroscopy (FT-IR), UV-visible spectra, Raman spectroscopy, and electrochemical technologies, in which the electrochemical sensor based on PolyDTTF was successfully constructed and demonstrated a significant electrocatalytic effect on nitrite. The influence of pH value, electrodeposition scanning times, scanning speed, and potential on the electrochemical behavior of nitrite were investigated in detail. Furthermore, the nitrite sensor exhibits excellent responses proportional to nitrite concentrations (R2 = 0.9972) over a concentration range of 5.5 × 10-9 ~ 3.5 × 10-5 M with a detection limit (LOD) of 2 nM, and has extremely good anti-interference ability for nitrite detection. This proposed sensor can be used to detect nitrite in actual samples, opening the possibility for applications in the food industry and environmental analysis.

2.
Histopathology ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637146

RESUMO

AIMS: It is unknown whether Epstein-Barr virus (EBV) infection can occur in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, also known as double-hit or triple-hit lymphoma (DHL/THL). METHODS AND RESULTS: Here we report 16 cases of EBV+ DHL/THL from screening 846 cases of DHL/THL and obtaining additional EBV+ cases through multi-institutional collaboration: 8 MYC/BCL2 DHL, 6 MYC/BCL6 DHL, and 2 THL. There were 8 men and 8 women with a median age of 65 years (range, 32-86). Two patients had a history of follicular lymphoma and one had AIDS. Nine of 14 patients had an International Prognostic Index of ≥3. Half of the cases showed high-grade/Burkitt-like morphology and the other half diffuse large B-cell lymphoma morphology. By immunohistochemistry, the lymphoma cells were positive for MYC (n=14/16), BCL2 (n=12/16), BCL6 (n=14/16), CD10 (n=13/16), and MUM1 (n=6/14). By Hans algorithm, 13 cases were classified as GCB and 3 as non-GCB. The lymphomas frequently showed an EBV latency type I with a median EBV-encoded small RNAs of 80% positive cells (range, 20-100%). After a median follow-up of 36.3 months (range, 2.0-41.6), 7 patients died with a median survival of 15.4 months (range, 3.4-47.3) after diagnosis of EBV+ DHL/THL. Five of 6 patients with MYC/BCL6 DHL were alive including 4 in complete remission. In contrast, only 4/10 patients with MYC/BCL2 DHL or THL were alive including 2 in complete remission. The median survival in patients with MYC/BCL6 DHL was unreached and was 21.6 months in patients with MYC/BCL2 DHL or THL. CONCLUSIONS: EBV infection in DHL/THL is rare (~1.5%). Cases of EBV+ DHL/THL are largely similar to their EBV-negative counterparts clinicopathologically. Our findings expand the spectrum of EBV+ B-cell lymphomas currently recognized in the WHO classification and suggest differences between EBV+ MYC/BCL2 and MYC/BCL6 DHL that may have therapeutic implications.

3.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3949-3959, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472272

RESUMO

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.


Assuntos
Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
4.
Phytomedicine ; 92: 153739, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34592488

RESUMO

BACKGROUND: Triptolide is naturally isolated from Tripterygium wilfordii Hook F., possessing multiple biological activities. Hepatotoxicity is one of the main side effects of triptolide. However, the effect of triptolide on nonalcoholic fatty liver disease remains unknown (NAFLD). PURPOSE: This study aimed to observe the amelioration of triptolide against NAFLD and investigate the engaged mechanism. METHODS: Two typical animal models of NAFLD, obese db/db mice and methionine/choline-deficient (MCD) diet-fed mice, were used. Hepatic steatosis, inflammation, and fibrosis were evaluated by H&E and Masson staining. Oil red O staining and lipid extraction analysis were used to detect fat content in mice livers. Expression of lipid metabolism, inflammatory and fibrogenic genes was also detected by Real-time PCR and Western blotting, respectively. Phosphoproteomics, molecular docking, and TR-FRET assay were performed to provide further insight into how triptolide improved NAFLD. RESULTS: Intraperitoneal injection of triptolide at a daily dose of 50 µg/kg significantly alleviated MCD diet-induced nonalcoholic steatohepatitis (NASH), but 100 µg/kg triptolide caused severe hepatotoxicity. Pathological staining confirmed low-dose triptolide treatment reducing hepatic lipid deposition, inflammation, and fibrosis in NASH. Serum biochemical analysis revealed a reduction in the level of liver enzymes and bilirubin. MCD also induced rising expression of typical genes and proteins related to fibrosis (fibronectin, α-SMA, collagens, TGF-ß) and inflammation (ILs, TNF-α, MCP-1), which was suppressed by low-dose triptolide. Data from the proteomics/phosphoproteomics and TR-FRET assay indicated triptolide was a potential allosteric AMPK agonist to increase the phosphorylation on Thr172 residue, with the EC50 of 277.78 µM and 231.02 µM for AMPKα1 and AMPKα2, respectively. Moreover, triptolide exhibited an ability to activate AMPK and further led to increasing ACC1 phosphorylation in the liver. The positive results that triptolide ameliorated hepatic lipogenesis, fatty acid oxidation, and fibrosis of NAFLD via activating AMPK were further confirmed in db/db mice with 10-week intervention (50 µg/kg, i.v., twice a week). CONCLUSION: This study demonstrates that dose-related triptolide as an allosteric AMPK agonist has the potential to alleviate NAFLD without hepatotoxicity.

5.
Int J Sports Med ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553365

RESUMO

We aimed to examine speed of movement and its interactive association with fatness to changes in cardiometabolic risk factors over one year in children. The analysis included 8345 children aged 6-13 years. Cardiometabolic risk score was computed by summing Z-scores of waist circumference, the average of systolic and diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol (multiplied by -1), and triglycerides. Both high baseline and improvement in speed of movement were associated with favourable changes in percent body fat, lipids, and cardiometabolic risk score. Percentages of the association between baseline speed of movement and changes in cardiometabolic risk score, triglycerides, and high-density lipoprotein cholesterol explained by baseline BMI were 24.6% (19.6-29.1%), 26.2% (19.7-31.1%), and 12.5% (9.6-15.4%), respectively. The corresponding number for percent body fat was 47.0% (40.4-54.1%), 43.3% (36.7-51.7%), and 29.8% (25.0-34.6%), respectively. Speed of movement mediated the association between fatness and cardiometabolic risk factors. Improved speed of movement was associated with a lower increase in blood pressure in obese children only. Speed of movement is a strong predictor of changes in cardiometabolic risk factors. Fatness and speed of movement are interactively associated with cardiometabolic risk factors. Speed of movement may attenuate the positive association between fatness and blood pressure.

6.
Int J Nanomedicine ; 16: 6441-6453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34584410

RESUMO

Background: Renal fibrosis is the common pathway in chronic kidney diseases progression to end-stage renal disease, but to date, no clinical drug for its treatment is approved. It has been demonstrated that the inhibitor of proto-oncogene Ras, farnesylthiosalicylic acid (FTS), shows therapeutic potential for renal fibrosis, but its application was hindered by the water-insolubility and low bioavailability. Hence, in this study, we improved these properties of FTS by encapsulating it into bovine serum albumin nanoparticles (AN-FTS) and tested its therapeutic effect in renal fibrosis. Methods: AN-FTS was developed using a classic emulsification-solvent ultrasonication. The pharmacokinetics of DiD-loaded albumin nanoparticle were investigated in SD rats. The biodistribution and therapeutic efficacy of AN-FTS was assessed in a mouse model of renal fibrosis induced by unilateral ureteral obstruction (UUO). Results: AN-FTS showed a uniform spherical shape with the size of 100.6 ± 1.12 nm and PDI < 0.25. In vitro, AN-FTS displayed stronger inhibitory effects on the activation of renal fibroblasts cells NRK-49F than free FTS. In vivo, AN-FTS showed significantly higher peak concentration and area under the concentration-time curve. After intravenous administration to UUO-induced renal fibrosis mice, AN-FTS accumulated preferentially in the fibrotic kidney, and alleviated renal fibrosis and inflammation significantly more than the free drug. Mechanistically, the improved anti-fibrosis effect of AN-FTS was associated with greater inhibition in renal epithelial-to-mesenchymal transformation process via Ras/Raf1/p38 signaling pathway. Conclusion: The study reveals that AN-FTS is capable of delivering FTS to fibrotic kidney and showed superior therapeutic efficacy for renal fibrosis.

7.
Am J Clin Nutr ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582546

RESUMO

BACKGROUND: The associations between nut consumption and cancer risk have not been extensively investigated. OBJECTIVES: We aimed to examine the associations between nut consumption, especially specific types of nuts (peanut, tree nut, walnut, and tree nut other than walnut), and cancer risk. METHODS: Nut consumption was assessed by FFQ at baseline and updated every 2-4 y in the Nurses' Health Study (1980-2014), the Nurses' Health Study II (1991-2015), and the Health Professionals Follow-up Study (1986-2018). We examined the associations between the intake of total and specific types of nuts and risk of total cancer and common cancers, including lung, colorectal, breast, bladder, and aggressive prostate cancer. Cox proportional-hazards models were used to obtain the HRs and 95% CIs in each cohort as well as pooled. RESULTS: During 5,873,671 person-years of follow-up in 180,832 women and 45,560 men, we documented 44,561 incident cancer cases. As compared with nonconsumers, the pooled multivariable HRs of total nut consumption for ≥5 times/wk were 0.99 (95% CI: 0.94, 1.04; P-trend = 0.54) for total cancer, 0.88 (95% CI: 0.74, 1.04; P-trend = 0.18) for lung cancer, 1.07 (95% CI: 0.92, 1.26; P-trend = 0.89) for colorectal cancer, 0.90 (95% CI: 0.71, 1.14; P-trend = 0.65) for bladder cancer, 0.96 (95% CI: 0.85, 1.08; P-trend = 0.36) for breast cancer, and 1.18 (95% CI: 0.92, 1.51; P-trend = 0.52) for aggressive prostate cancer. CONCLUSIONS: In 3 large prospective cohorts, frequent nut consumption was not associated with risk of total cancer and common individual cancers.

8.
Am J Otolaryngol ; 43(1): 103231, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34537512

RESUMO

OBJECTIVE: The objective of this study was evaluate the short-and long-term graft outcome and complications of endoscopic modified perichondrium-cartilage sandwich graft for repairing chronic subtotal and total perforations. STUDY DESIGN: Prospective case series. MATERIALS AND METHODS: 135 patients with chronic subtotal and total perforations who underwent endoscopic modified perichondrium-cartilage sandwich graft technique. The graft success rate, hearing outcome, and complications were evaluated at postoperative 6 and 24 months. RESULTS: 124 patients were finally included in this study. The graft success rate was 96.3% in subtotal perforation and 97.7% in total perforation (P = 0.874), with an overall success rate of 96.8% at postoperative 6 months. The graft success rate was 95.8% (68/71) in subtotal perforation and 94.9% (37/39) in total perforation (P = 0.795), with an overall success rate of 95.5% (105/110) at postoperative 24 months. The mean ABG improved from 28.0 ± 5.3 dB preoperatively to 14.9 ± 4.8 dB postoperatively 12 months (P < 0.05) for subtotal perforations; from 33.4 ± 7.4 dB preoperatively to 16.1 ± 2.4 dB postoperatively 12 months (P < 0.05) for total perforations. No graft-related complications (e.g., graft lateralization, significant blunting, graft medialization) were encountered during the follow-up period. Of the 110 patients, temporal bone CT revealed well pneumatization of the middle ear and mastoid region. However, graft keratin pearl was noticed in 1.8% (2/110) patients. CONCLUSIONS: Endoscopic modified perichondrium-cartilage sandwich graft for repairing subtotal and total perforations had excellent short and long-term graft success rate with less time-consuming and minimal complications.

9.
Neural Netw ; 144: 455-464, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34583101

RESUMO

Pancreatic cancer is the deadliest cancer type with a five-year survival rate of less than 9%. Detection of tumor margins plays an essential role in the success of surgical resection. However, histopathological assessment is time-consuming, expensive, and labor-intensive. We constructed a lab-designed, hand-held Raman spectroscopic system that could enable intraoperative tissue diagnosis using convolutional neural network (CNN) models to efficiently distinguish between cancerous and normal pancreatic tissue. To our best knowledge, this is the first reported effort to diagnose pancreatic cancer by CNN-aided spontaneous Raman scattering with a lab-developed system designed for intraoperative applications. Classification based on the original one-dimensional (1D) Raman, two-dimensional (2D) Raman images, and the first principal component (PC1) from the principal component analysis on the 2D image, could all achieve high performance: the testing sensitivity, specificity, and accuracy were over 95%, and the area under the curve approached 0.99. Although CNN models often show great success in classification, it has always been challenging to visualize the CNN features in these models, which has never been achieved in the Raman spectroscopy application in cancer diagnosis. By studying individual Raman regions and by extracting and visualizing CNN features from max-pooling layers, we identified critical Raman peaks that could aid in the classification of cancerous and noncancerous tissues. 2D Raman PC1 yielded more critical peaks for pancreatic cancer identification than that of 1D Raman, as the Raman intensity was amplified by 2D Raman PC1. To our best knowledge, the feature visualization was achieved for the first time in the field of CNN-aided spontaneous Raman spectroscopy for cancer diagnosis. Based on these CNN feature peaks and their frequency at specific wavenumbers, pancreatic cancerous tissue was found to contain more biochemical components related to the protein contents (particularly collagen), whereas normal pancreatic tissue was found to contain more lipids and nucleic acid (particularly deoxyribonucleic acid/ribonucleic acid). Overall, the CNN model in combination with Raman spectroscopy could serve as a useful tool for the extraction of key features that can help differentiate pancreatic cancer from a normal pancreas.

10.
BMC Gastroenterol ; 21(1): 335, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454434

RESUMO

BACKGROUND: Although salt plays an important role in maintaining the normal physiological metabolism of the human body, many abnormalities in the liver caused by a high-salt diet, especially with normal pathological results, are not well characterized. METHODS: Eight-week-old female C57BL/6 mice were randomly divided into a normal group and a high salt group. These groups were then fed with normal or sodium-rich chow (containing 6% NaCl) for 6 weeks. Liver injury was evaluated, and the influences of a high-salt diet on the liver were analyzed by transcriptome sequencing at the end of week 6. RESULTS: We found that although no liver parenchymal injury could be found after high-salt feeding, many metabolic abnormalities had formed based on transcriptome sequencing results. GO and KEGG enrichment analyses of differentially expressed genes revealed that at least 15 enzymatic activities and the metabolism of multiple substances were affected by a high-salt diet. Moreover, a variety of signaling and metabolic pathways, as well as numerous biological functions, were involved in liver dysfunction due to a high-salt diet. This included some known pathways and many novel ones, such as retinol metabolism, linoleic acid metabolism, steroid hormone biosynthesis, and signaling pathways. CONCLUSIONS: A high-salt diet can induce serious abnormal liver metabolic activities in mice at the transcriptional level, although substantial physical damage may not yet be visible. This study, to our knowledge, was the first to reveal the impact of a high-salt diet on the liver at the omics level, and provides theoretical support for potential clinical risk evaluation, pathogenic mechanisms, and drug design for combating liver dysfunction. This study also provides a serious candidate direction for further research on the physiological impacts of high-salt diets.


Assuntos
Cloreto de Sódio , Transcriptoma , Animais , Dieta , Feminino , Fígado/metabolismo , Redes e Vias Metabólicas/genética , Camundongos , Camundongos Endogâmicos C57BL , Cloreto de Sódio/metabolismo
11.
Ecotoxicol Environ Saf ; 224: 112634, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34392153

RESUMO

Nickel is a heavy metal element extensively distributed in the environment and widely used in modern life. Divalent nickel is one of the most widespread forms of nickel and has been reported as toxic to various tissues. However, whether exposure to divalent nickel negatively affects ovarian homeostasis and oocyte quality remains unclear. In this study, we found that 3 weeks of nickel sulfate exposure affected body growth and decreased the weight and coefficient of the ovary, and increased atretic follicles exhibiting enhanced apoptosis in granulosa cells. Further studies have found that nickel sulfate triggered ovarian fibrosis and inflammation via transforming growth factor-ß1 and nuclear factor-κB pathways, and reduced oocyte development ability. In addition, nickel sulfate increased the level of reactive oxygen species, which induced DNA damage and early apoptosis. Moreover, it was found that nickel sulfate caused damage to the mitochondria showing aberrant morphology, distribution and membrane potential while decreased levels of histone methylation. To summarize, our results indicated that nickel sulfate exposure triggered ovarian fibrosis and inflammation and caused structural and functional disorders of mitochondria in oocytes, which consequently disturbed ovarian homeostasis and follicle development and decreased oocyte quality.

12.
Nutrients ; 13(8)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34444859

RESUMO

Walnut consumption is associated with health benefits. We aimed to (1) examine the association between walnut consumption and mortality and (2) estimate life expectancy in relation to walnut consumption in U.S. adults. We included 67,014 women of the Nurses' Health Study (1998-2018) and 26,326 men of the Health Professionals Follow-up Study (1998-2018) who were free of cancer, heart disease, and stroke at baseline. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During up to 20 years of follow-up, we documented 30,263 deaths. The hazard ratios for total mortality across categories of walnut intake (servings/week), as compared to non-consumers, were 0.95 (95% confidence interval (CI), 0.91, 0.98) for <1 serving/week, 0.94 (95% CI, 0.89, 0.99) for 1 serving/week, 0.87 (95% CI, 0.82, 0.93) for 2-4 servings/week, and 0.86 (95% CI, 0.79, 0.93) for >=5 servings/week (p for trend <0.0001). A greater life expectancy at age 60 (1.30 years in women and 1.26 years in men) was observed among those who consumed walnuts more than 5 servings/week compared to non-consumers. Higher walnut consumption was associated with a lower risk of total and CVD mortality and a greater gained life expectancy among U.S. elder adults.


Assuntos
Dieta/mortalidade , Juglans , Expectativa de Vida/tendências , Mortalidade/tendências , Nozes , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Causas de Morte , Dieta/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Regressão , Estados Unidos
13.
Eur J Pharmacol ; 909: 174411, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34390710

RESUMO

Advanced Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a poor prognosis. The anti-malaria compounds dihydroartemisinin (DHA) have shown to regulate multiple targets and signaling pathways in cancers, but a global view of its mechanism of action remains elusive. In present study, we integrated network pharmacology and in vitro and in vivo experimental models to investigate the mechanisms of DHA in preventing NSCLC proliferation. We first proved that DHA inhibits the growth of lung cancer via inducing cell apoptosis and cell cycle arrest, then we integrated information from publicly available databases to predict interactions between DHA and its potential targets in NSCLC, as well as the signaling pathways involved. In this way we identified 118 common targets of DHA and NSCLC, and further analyzed with the correlation between these targets by KEGG and GO analysis. Our data indicate that mTOR/HIF-1α signaling is one of potential critical pathways involved in DHA-induced tumor inhibition in NSCLC. Finally, the data from human and mouse lung cancer cell lines and in mouse Lewis lung cancer models showed that DHA does decrease the expression level of mTOR and HIF-1α which supported the potential roles of mTOR/HIF-1α Signaling in NSCLC and deserves further investigation.

14.
J Am Coll Cardiol ; 78(7): 666-678, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34384548

RESUMO

BACKGROUND: Evidence regarding lignan consumption in relation to coronary heart disease (CHD) risk remains limited and mixed. OBJECTIVES: The aim of this study was to prospectively examine associations between lignan intake and CHD risk in U.S. men and women. METHODS: We prospectively followed 214,108 men and women in 3 cohorts who did not have cardiovascular disease or cancer at baseline. Diet was repeatedly assessed using a validated food frequency questionnaire every 2-4 years since baseline. RESULTS: During 5,517,225 person-years of follow-up, we documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarction and 3,961 fatal CHD cases. In multivariable-adjusted analyses, comparing extreme quintiles, the pooled hazard ratios of CHD were 0.85 (95% CI: 0.79-0.92) for total lignans, 0.76 (95% CI: 0.71-0.82) for matairesinol, 0.87 (95% CI: 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI: 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83-0.95) for lariciresinol (all P values for trend ≤0.003). Nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: the risk reduction plateaued at intakes above approximately 300 µg/d, 10 µg/d, and 100 µg/d, respectively (P < 0.01 for all nonlinearity). The inverse associations for total lignan intake appeared to be more apparent among participants with higher total fiber intake (P = 0.04 for interaction). In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher. CONCLUSIONS: Increased long-term intake of lignans was associated with a significantly lower risk of total CHD in both men and women. Possible synergistic effects may exist between lignan and fiber intake in relation to CHD risk reduction, possibly through enhancing the production of enterolignans.

15.
Biochem Pharmacol ; 192: 114736, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34411567

RESUMO

Reprogramming of energy metabolism is a hallmarkofcancer, and the pentose phosphate pathway (PPP) is a major glucose metabolic pathway important for meeting the cellular demands of biosynthesis and anti-oxidant defense. Our previous study showed that phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A) plays an important role in glioblastoma cell survival and growth under cellular energy stress condition. However, the crucial functions of PIKE-A in cancer energy metabolism are poorly understood.In the present study, we show that PIKE-A promotes DNA biosynthesis, NADPH production and inhibits reactive oxygen species (ROS) production, leading to increasing proliferation and growth of glioblastoma cell and suppressing cellular senescence. Mechanistically, PIKE-A binds to STAT3 and stimulates its phosphorylation mediated by tyrosine kinase Fyn, which enhances transcription of the rate-limitting enzyme glucose-6-phosphate dehydrogenase (G6PD) in the PPP. Finally, targeting PIKE-A-G6PD axis sensitizes glioblastoma to temozolomide (TMZ)treatment. This study reveals that STAT3 is a novel binding partner of PIKE-A which recruits Fyn to phosphorylate STAT3, contributing to the expression of G6PD, leading to promoting tumor growth and suppressing cellular senescence. Thus, the PIKE-A/STAT3/G6PD axis strongly links the PPP to carcinogenesis and may become a promising cancer therapeutic target.

16.
Lancet ; 398(10302): 747-758, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454673

RESUMO

BACKGROUND: The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19. METHODS: We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes. FINDINGS: 1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls. INTERPRETATION: Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.


Assuntos
COVID-19/complicações , Sobreviventes , Idoso , Ansiedade/etiologia , COVID-19/fisiopatologia , COVID-19/psicologia , Depressão/etiologia , Tolerância ao Exercício , Fadiga/etiologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Qualidade de Vida , SARS-CoV-2 , Teste de Caminhada
18.
Gastroenterology ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34389341

RESUMO

BACKGROUND & AIMS: China has the largest number of incident liver, esophageal, gastric, and colorectal cancer cases in 2020. Examining the time trend of relevant lifestyle risk factors would help project the trend of these gastrointestinal (GI) cancer incidence in China. METHODS: We estimated the time trend of the lifestyle factors based on the China Health and Nutrition Survey 1991 to 2011. We applied the comparative risk assessment method to estimate the population attributable fraction of GI cancers attributable to each risk factor. We also projected the prevalence of lifestyle factors and the associated burden of GI cancer from 2011 to 2031. RESULTS: In 2011, 56.5% of colorectal, 59.8% of gastric, 48.5% of esophageal, and 35.2% of liver cancer in China were attributable to the lifestyle risk factors under study. Smoking, sodium intake, low vegetable intake, and low fruit intake have improved over time but remained far from optimal and are expected to be responsible for 170,000, 35,000, 22,000, and 50,000 GI cancer cases in 2031, respectively. High body mass index, red and processed meat consumption, and low physical activity are expected to contribute increasingly more GI cancer, accounting for 142,000, 185,000, 60,000, and 53,000 cases in 2031, respectively. The estimated population attributable fraction for all risk factors in 2031 is 52.1%. CONCLUSIONS: Lifestyle risk factors have had an impact on the risk of GI cancer in China, and the impact is projected to increase. If everyone could adhere to the optimal lifestyle, half of all GI cancer events would be prevented by year 2031.

19.
Reprod Biomed Online ; 43(2): 197-204, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34253450

RESUMO

This meta-analysis investigated whether a previous Caesarean section has an impact on the outcomes of treatment with assisted reproductive technology (ART). PubMed, Embase, Cochrane Library, Web of Science and Google Scholar were searched. Clinical trials published in English up to May 2020 were included. Seven studies performed between 2016 and 2020 met all the inclusion criteria. It was found that previous Caesarean section leads to significantly decreased clinical pregnancy rate (CPR) (risk ratio [RR] 0.86; 95% confidence interval [CI], 0.81, 0.92; P < 0.00001) and live birth rate (LBR) (RR 0.80; 95% CI 0.73, 0.86; P < 0.00001). Caesarean section increased the miscarriage rate (RR 1.39; 95% CI 1.18, 1.64; P < 0.0001), and difficult transfer (RR 8.23; 95% CI 4.63, 14.65; P < 0.00001) after ART compared with women who had previous vaginal delivery. The combined results also showed similar endometrial thickness, number of oocytes retrieved, implantation rate, ectopic pregnancy rate, preterm birth and stillbirth between women with previous Caesarean section and women with previous vaginal delivery. In conclusion, Caesarean sections have a detrimental effect on CPR and LBR, and increase the risk of miscarriage and difficult transfer. The indications for Caesarean section should be strictly controlled, and full consultation should be provided to pregnant women. Further studies with stratification analysis of twin and single pregnancies are needed to evaluate the impact of Caesarean section.

20.
Aesthetic Plast Surg ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312695

RESUMO

Once cartilage is damaged, its self-repair capacity is very limited. The strategy of tissue engineering has brought a new idea for repairing cartilage defect and cartilage regeneration. In particular, nasal cartilage regeneration is a challenge because of the steady increase in nasal reconstruction after oncologic resection, trauma, or rhinoplasty. From this perspective, three-dimensional (3D) printing has emerged as a promising technology to address the complexity of nasal cartilage regeneration, using patient's image data and computer-aided deposition of cells and biomaterials to precisely fabricate complex, personalized tissue-engineered constructs. In this review, we summarized the major progress of three prevalent 3D printing approaches, including inkjet-based printing, extrusion-based printing and laser-assisted printing. Examples are highlighted to illustrate 3D printing for nasal cartilage regeneration, with special focus on the selection of seeded cell, scaffolds and growth factors. The purpose of this paper is to systematically review recent research about the challenges and progress and look forward to the future of 3D printing techniques for nasal cartilage regeneration.Level of Evidence III This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

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