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1.
Gene ; 807: 145934, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34478820

RESUMO

Residual feed intake (RFI) is a measurement of feed efficiency, and is inversely correlated with feed efficiency. The differentially expressed genes (DEGs) associated with RFI vary substantially among studies, posing great challenges in finding the RFI-related marker genes. This study attempted to resolve this issue by integrating and comparing the multiple transcriptome sequencing data associated with RFI in the cattle liver, using differential, functional enrichment, protein-protein interaction (PPI) network, weighted co-expression network (WGCNA), and gene set enrichment analyses (GSEA) to identify the candidate genes and functional enrichment pathways that are closely associated with RFI. Four candidate genes namely SHC1, GPX4, ACADL, and IGF1 were identified and validated as the marker genes for RFI. Four functional enrichment pathways, namely the fatty acid metabolism, sugar metabolism, energy metabolism, and protein ubiquitination were also found to be closely related to RFI. This study identified several genes and signaling pathways with shared characteristics, which will provide new insights into the molecular mechanisms related to the regulation of feed efficiency, and provide basis for molecular markers related to feed efficiency in beef cattle.

2.
Chin J Integr Med ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596802

RESUMO

OBJECTIVE: To compare the safety differences between Chinese medicine (CM) and Western medicine (WM) based on Chinese Spontaneous Reporting Database (CSRD). METHODS: Reports of adverse events (AEs) caused by CM and WM in the CSRD between 2010 and 2011 were selected. The following assessment indicators were constructed: the proportion of serious AEs (PSE), the average number of AEs (ANA), and the coverage rate of AEs (CRA). Further comparisons were also conducted, including the drugs with the most reported serious AEs, the AEs with the biggest report number, and the 5 serious AEs of interest (including death, anaphylactic shock, coma, dyspnea and abnormal liver function). RESULTS: The PSE, ANA and CRA of WM were 1.09, 8.23 and 2.35 times higher than those of CM, respectively. The top 10 drugs with the most serious AEs were mainly injections for CM and antibiotics for WM. The AEs with the most reports were rash, pruritus, nausea, dizziness and vomiting for both CM and WM. The proportions of CM and WM in anaphylactic shock and coma were similar. For abnormal liver function and death, the proportions of WM were 5.47 and 3.00 times higher than those of CM, respectively. CONCLUSION: Based on CSRD, CM was safer than WM at the average level from the perspective of adverse drug reactions.

3.
J Phys Chem A ; 125(40): 8816-8826, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34606278

RESUMO

The photophysical mechanisms of tellurium-substituted uracils were studied at the multistate complete-active-space second-order perturbation level with a particular focus on how the position and number of tellurium substitutions affect their nonadiabatic relaxation processes. Electronic structure analysis reveals that the lowest several excited states are closely concerned with the n and π orbitals at the Te7-C2 [Te8-C4] moiety of 2-tellurouracil (2TeU) [4TeU and 24TeU]. Both planar and twisted minima were optimized for 2TeU, whereas only planar ones were obtained for 4TeU and 24TeU, except for a twisted T1 minimum of 4TeU. Based on intersection structures and linearly interpolated internal coordinate paths, we proposed several feasible excited-state deactivation paths. It is found that the relaxation channels for 2TeU are more complicated than those of 4TeU and 24TeU. The electronic population transfer to the T1 state for 2TeU is easier than that for 4TeU and 24TeU in consideration of the barrier heights from the S2 Franck-Condon point to the S2/S1 or S2/T2 intersections. In addition, the recovery of the ground state from the T1 state for 2TeU will be more efficient than that for the other two systems as well.

4.
Bioorg Chem ; 116: 105384, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34601294

RESUMO

The Src homology-2 domain containing-protein tyrosine phosphatase-2 (SHP2) is a convergent node for oncogenic cell-signaling cascades including the PD-L1/PD-1 pathway. As an oncoprotein as well as a potential immunomodulator, SHP2 has now emerged as an attractive target for novel anti-cancer agents. Although significant progress has been made in identifying chemotypes of SHP2 inhibitors, these specific compounds might not be clinically useful to inhibit frequently encountered mutated SHP2 variants. Consequently, it is highly desirable to develop chemically different SHP2 inhibitors sensitive to SHP2 mutants. This work developed a new type of SHP2 inhibitors with 2,5-diaryl-1,3,4-oxadiazole scaffold. The representative compound 6l exhibited SHP2 inhibitory activity with IC50 of 2.73 ± 0.20 µM, showed about 1.56-fold, 5.26-fold, and 7.36-fold selectivity for SHP2 over SHP1, PTP1B and TCPTP respectively. Further investigations confirmed that 6l behaved as mixed-type inhibitor sensitive to leukemia cell TF-1 and inhibited SHP2 mediated cell signaling and proliferation. Molecular dynamics simulation provided more detailed information on the binding modes of compounds and SHP2 protein. These preliminary results could provide a possible opportunity for the development of novel SHP2 inhibitors sensitive to SHP2 mutants with optimal potency and improved pharmacological properties.

5.
Hereditas ; 158(1): 33, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465393

RESUMO

BACKGROUND: Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) has been proved to play a vital role in human cancers. Nevertheless, the exact role of ENTPD1 in thyroid carcinoma (THCA) remained unclear. This study aimed to evaluate its prognostic value and reveal the potential regulatory mechanism in THCA. RESULTS: (1) Higher expression of ENTPD1 was found in THCA tissue compared with normal tissue (all P < 0.05). ENTPD1 expression was associated with age, sub-type and clinical stage of THCA patients (all P < 0.05). Immunohistochemistry showed its higher expression in patients with early stage. (2) ENTPD1 high expression was associated with favorable overall survival of THCA patients (all P < 0.05), especially for male patients and those with advanced stage, B-cells and Natural killer T-cells decreased (all P < 0.05). (3) Pathway analysis indicated that ENTPD1 mainly participated in metabolic process and negatively regulated metabolism-related pathway such as butanoate metabolism, pyruvate metabolism and fatty acid metabolism ((all P < 0.05). (4) ENTPD1 appeared genetic alteration in THCA, and the main mutation type of ENTPD1 was missense substitution (15.89%). (5) A weak correlation between ENTPD1 expression and methylation was found (P < 0.001). Methylation of ENTPD1 in THCA was lower than in normal group (P < 0.001), but it did not correlate with any clinical phenotypes of THCA patients. CONCLUSIONS: ENTPD1 was highly expressed in THCA, and ENTPD1 high expression contributed to the prognosis of THCA patients. The present study inferred that ENTPD1 might serve as a metabolism-related gene and play a critical role in THCA through regulating metabolic pathways.

6.
Mol Pharm ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579532

RESUMO

Stemness and metastasis are the two main challenges in cancer therapy and are related to disease relapse post-treatment. They both have a strong correlation with chemoresistance and poor prognosis, ultimately leading to treatment failure. It has been reported that chemotherapy can induce stemness and metastasis in many cancer types, especially treatment with the chemotherapeutic agent doxorubicin (DOX) in breast cancer. A combination treatment is an efficient and elegant approach in cancer therapy through simultaneous delivery of two or more drugs with a delivery system for its synergistic effect, which is not an additive of two individual drugs. Herein, we report a combinatorial system with DOX and all-trans retinoic acid (ATRA) to address both of the above issues. As a common critical regulatory factor for oncogenic signal transduction pathways, Pin1 is a specific isomerase highly expressed within various tumor cells. ATRA, a newly identified Pin1 inhibitor, can abolish several oncogenic pathways by effectively inhibiting and degrading overexpressed Pin1. We successfully developed a folic acid (FA)-modified chitosan (CSO)-derived polymer (FA-CSOSA) and obtained FA-CSOSA/DOX and FA-CSOSA/ATRA drug-loaded micelles. FA modification can improve the uptake of the nanoparticles in tumor cells and tumor sites via folate receptor-mediated cell internalization. Compared to treatment with DOX alone, the combined treatment induced 4T1 cell apoptosis in a synergistic manner. Reduced stemness-related protein expression and inhibited metastasis were observed during treatment with FA-CSOSA/DOX and FA-CSOSA/ATRA and were found to be associated with Pin1. Further in vivo experiments showed that treatment with FA-CSOSA/DOX and FA-CSOSA/ATRA resulted in 85.5% tumor inhibition, which was 2.5-fold greater than that of cells treated with DOX·HCl alone. This work presents a new paradigm for addressing chemotherapy-induced side effects via degradation of Pin1 induced by tumor-targeted delivery of DOX and ATRA.

7.
Virol Sin ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523109

RESUMO

Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality in children worldwide. In this study, we aimed to describe the aetiology of viral infection of pediatric CAP in Chinese mainland. During November 2014 to June 2016, the prospective study was conducted in 13 hospitals. The hospitalized children under 18 years old who met the criteria for CAP were enrolled. The throat swabs or nasopharyngeal aspirates (NPAs) were collected which were then screened 18 respiratory viruses using multiplex PCR assay. Viral pathogens were present in 56.6% (1539/2721) of the enrolled cases, with the detection rate of single virus in 39.8% of the cases and multiple viruses in 16.8% of the cases. The most frequently detected virus was respiratory syncytial virus (RSV) (15.2%, 414/2721). The highest detection rate of virus was in < 6-month-age group (70.7%, 292/413). RSV, human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs) and influenza B virus (Flu B) showed the similar prevalence patterns both in north and south China, but HPIVs, Flu A, human bocavirus (HBoV), human adenovirus (HAdV) and human coronaviruses (HCoVs) showed the distinct circulating patterns in north and south China. Human enterovirus/human rhinovirus (HEV/HRV) (27.6%, 27/98), HBoV (18.4%, 18/98), RSV (16.3%, 16/98) and HMPV (14.3%, 14/98) were the most commonly detected viruses in severe pneumonia cases with single virus infection. In conclusion, viral pathogens are frequently detected in pediatric CAP cases and may therefore play a vital role in the aetiology of CAP. RSV was the most important virus in hospitalized children with CAP in Chinese mainland.

8.
BMJ Open ; 11(9): e051499, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521675

RESUMO

OBJECTION: The objective of this study was to assess attitudes towards the use of Traditional Chinese Medicine (TCM) for COVID-19 among Chinese immigrants in Canada during the early stage of the COVID-19 pandemic. METHODS: A cross-sectional study was conducted in April 2020 in Canada. Individuals aged 16 or older who were of Chinese origin and living in Canada at the time of the survey were invited to participate in an online survey. Descriptive and univariate statistics were performed to describe participant attitudes towards various preventive and treatment measures for COVID-19. Multiple logistic regression was used to identify independent associations with sociodemographic factors and attitudes. RESULTS: A total of 754 eligible respondents were included in the analysis. 65.8% of the participants were female, 77.2% had a university degree or higher and 28.6% were 55 years of age or older. Overall, 48.8% of the study participants believed that TCM was effective in preventing COVID-19% and 46.2% would use TCM if they had COVID-19-related symptoms. However, the corresponding numbers for western medicine were 20.8% and 39.9%, which were statistically lower (p<0.01). Older participants (55+vs <35, OR=3.55 (95% CI 2.05 to 6.14); 35-54 vs <35, OR=1.98 (95% CI 1.27 to 3.08)) and those who were dissatisfied with their income (OR=2.47(95% CI 1.56 to 3.92)) were more likely to believe TCM was effective against COVID-19. Similarly, older participants (55+vs <35, OR=3.13 (95% CI 1.79 to 5.46); 35-54 vs <35, OR=2.25 (95% CI 1.35 to 3.74)), females (OR=1.60 (95% CI 1.15 to 2.23)), and those born in mainland China (OR=10.49 (95% CI 2.32 to 47.39)) were more likely to use TCM if they had symptoms of COVID-19. CONCLUSION: Despite the lack of scientific evidence to support its use, TCM was widely believed by Chinese immigrants in Canada to be an effective means of preventing COVID-19 and many also stated they would use it if they were experiencing symptoms of COVID-19.


Assuntos
COVID-19 , Emigrantes e Imigrantes , Atitude , Canadá , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Medicina Tradicional Chinesa , Pandemias , SARS-CoV-2
9.
Dev Cell ; 56(18): 2592-2606.e7, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34508658

RESUMO

Membrane contact between intracellular organelles is important in mediating organelle communication. However, the assembly of molecular machinery at membrane contact site and its internal organization correlating with its functional activity remain unclear. Here, we demonstrate that a gel-like condensation of Cidec, a crucial protein for obesity development by facilitating lipid droplet (LD) fusion, occurs at the LD-LD contact site (LDCS) through phase separation. The homomeric interaction between the multivalent N terminus of Cidec is sufficient to promote its phase separation both in vivo and in vitro. Interestingly, Cidec condensation at LDCSs generates highly plastic and lipid-permeable fusion plates that are geometrically constrained by donor LDs. In addition, Cidec condensates are distributed unevenly in the fusion plate generating stochastic sub-compartments that may represent unique lipid passageways during LD fusion. We have thus uncovered the organization and functional significance of geometry-constrained Cidec phase separation in mediating LD fusion and lipid homeostasis.

10.
J Cell Mol Med ; 25(20): 9609-9616, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34545688

RESUMO

Hirschsprung disease (HSCR) is an infrequent congenital intestinal dysplasia. The known genetic variations are unable to fully explain the pathogenesis of HSCR. The α/ß-hydratase domain 1 (ABHD1) interferes with the proliferation and migration of intestinal stem cells. Docking protein 6 (DOK6) is involved in neurodevelopment through RET signalling pathway. We examined the association of ABHD1 and DOK6 genetic variants with HSCR using 1470 controls and 1473 HSCR patients from Southern Chinese children. The results clarified that DOK6 rs12968648 G allele significantly increased HSCR susceptibility, in the allelic model (p = 0.034; OR = 1.12, 95%CI = 1.01~1.24) and the dominant model (p = 0.038; OR = 1.12, 95%CI = 1.01~1.25). Clinical stratification analysis showed that rs12968648 G allele was associated with increased risk of short-segment HSCR (S-HSCR), in the allelic model (p = 0.028; OR = 1.14, 95%CI = 1.01~1.28) and the additive model (p = 0.030; OR = 1.14, 95%CI = 1.01~1.28). ABHD1 rs2304678 C allele had higher risk to develop total colonic aganglionosis (TCA) in the allelic model (p = 7.04E-03; OR = 1.67, 95%CI = 1.15~2.43) and the dominant model (p = 4.12E-03; OR = 1.93, 95%CI = 1.23~3.04). DOK6 rs12968648 and ABHD1 rs2304678 had significant intergenic synergistic effect according to logical regression (p = 0.0081; OR = 0.76, 95%CI = 0.63~0.93) and multifactor dimensionality reduction (MDR, p = 0.0045; OR = 1.25, 95%CI = 1.07~1.46). This study verified two susceptible variations of HSCR on ABHD1 and DOK6. Their roles in HSCR should be conducted in further studies.

11.
Bosn J Basic Med Sci ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582743

RESUMO

Testicular damage and testosterone secretion disorder are associated with diabetes mellitus. Quercetin,  a common flavonoid, has antioxidant, anti-cancer,  and blood sugar lowering effects. Therefore, this study aims to investigate the effect of quercetin on the reproductive system of male rats with diabetes in vivo and in vitro and elucidate its mechanism. Streptozotocin (STZ)  induction was used to establish a diabetes model in forty male Sprague Dawley (SD) rats, which were subsequently administered with 20 or 50 mg/kg of quercetin. Leydig cells of rat testes were treated by high glucose (HG) followed by 5 or 10 µM quercetin. Two doses of quercetin increased rat body weight and testicular weight, decreased blood glucose,and inhibited oxidative stress. RT-qPCR and Western blotting revealed that quercetin alleviated STZ-induced testicular damage and promoted testosterone synthesis. Both doses of quercetin reduced ROS and MDA levels, and increased SOD level in HG-treated cells. Both, in vivo and in vitro results confirmed that a high dose of quercetin was more effective. MiR-1306-5p was upregulated in testicular tissue of diabetic rats and HG-treated cells. 17ß-hydroxysteroid dehydrogenase (HSD17B7) was a target of miR-1306-5p and HSD17B7 was downregulated in STZ-induced rat tissues and HG-treated cells. HSD17B7 overexpression reversed the increase of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (Grp78) protein levels as well as eIF2α phosphorylation level and promotion of cell apoptosis caused by miR-1306-5p overexpression. Moreover, overexpression of HSD17B7 activated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) axis in HG-treated cells. In conclusion, quercetin inhibits ER stress and improves testosterone secretion disorder through the miR-1306-5p/HSD17B7 axis in diabetic rats.

12.
Ginekol Pol ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34541645

RESUMO

OBJECTIVES: The aim of this study was to investigate adverse pregnancy outcomes (APOs) and mother-to-child transmission (MTCT) of intrahepatic cholestasis in pregnancy (ICP) in hepatitis B virus infection (HBV) patients. MATERIAL AND METHODS: We performed a retrospective study at Beijing Youan Hospital in China from January 2010 through May 2017. A total of 232 patients were enrolled, including 106 HBV-infected ICP patients (Group H + C), 20 ICP patients (Group C) and 106 HBV-infected patients (Group H). Characteristics, APOs and MTCT rate of HBV were compared between groups. Group H + C was subdivided into 3 groups according to total bile acid (TBA) values and gestational age at diagnosis (GA). APOs were also compared within Group H + C according to TBA values and GA. RESULTS: There was no difference in live birth delivery mode and APOs between Groups H + C and C. Compared with Groups H, no difference was in live birth and MTCT rates of HBV. However, cesarean section delivery and APOs rates were higher in Group H+C (p < 0.05). Compared with Group H, adverse maternal outcomes such as postpartum hemorrhage and premature birth were more likely to occur in Group H + C (p < 0.001). Adverse fetal outcomes, the proportions of amniotic fluid reaching III degrees (AFIII), NICU admission, neonatal asphyxia and SGA were significantly higher among Group H + C than Group H (p < 0.05). Contamination of the AFIII rate increased with increasing TBA (p < 0.05). The rate of preterm birth and small for gestational age (SGA) was more common in GA 28-32 w compared with GA < 28 w and > 33 w (p < 0.01). CONCLUSIONS: H + C patients had more APOs than HBV patients, but the difference was not significant when compared with ICP patients. Although we did not find any difference in MTCT rate between H + C and HBV patients, active treatment to prevent neonatal asphyxia and HBV infection should be considered. Therefore, it is necessary to emphasize maternal and fetal monitoring during pregnancy and delivery.

13.
Virol Sin ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398429

RESUMO

Human respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015-2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A (RSV-A) was the predominant subgroup during this research period except in 2016. Totally, 535 sequences of the second hypervariable region (HVR-2) of the G gene were obtained. Combined with 182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1 (512), NA1 (6) and GA5 (3), respectively; while 196 RSV-B sequences fell in BA9 (193) and SAB4 (3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258Q and H266L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than 10%, while the sequences with T290I and T312I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites (296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015-2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

14.
Clin Ther ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34366153

RESUMO

PURPOSE: Henagliflozin is a highly selective and effective sodium glucose co-transporter (SGLT)-2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of meal intake on the pharmacokinetic properties of henagliflozin, and to understand the excretion pathways of henagliflozin in humans. METHODS: In this Phase I, randomized, open-label, single-dose, two-period crossover study, 12 healthy male Chinese volunteers were randomized to receive either henagliflozin 10 mg in the fasted condition followed by henagliflozin 10 mg in the fed condition, or the reverse schedule, with the two administrations separated by a washout period of at least 7 days. Samples of blood, urine, and feces were collected and analyzed for the investigation of the pharmacokinetic profile and excretion pathways in the fasted and fed conditions. Any adverse events that occurred throughout the study were recorded for tolerability assessment. FINDINGS: After the administration of a single oral dose of henagliflozin, mean (SD) plasma AUC0-∞ and Cmax were 1200 (274) h · ng/mL and 179 (48.8) ng/mL, respectively, in the fasted state and were decreased to 971 (245) h · ng/mL and 115 (34.2) ng/mL in the fed state. The fed/fasted ratios (90% CIs) of the geometric mean values of Cmax, AUC0-t, and AUC0-∞ were 64% (54%-76%), 80% (76%-85%), and 80% (76%-85%), respectively. The median (range) Tmax was prolonged from 1.5 (1-3) hours in the fasted condition to 2 (1.5-6) hours in the fed condition. Mass-balance testing revealed that henagliflozin was eliminated primarily as the parent drug in feces and as glucuronide metabolites in urine. In the fasted state, the cumulative excretion percentages of the parent drug and its metabolites to dose in feces and urine were 40.6% and 33.9%, respectively. The values in the fed condition were changed to 50.4% and 25.5%, respectively. These findings suggest that postprandial administration decreases the absorption rate and the extent of henagliflozin exposure in humans, but has no effect on the metabolism or elimination of the drug. IMPLICATIONS: In the present study, the consumption of a high-fat meal prior to henagliflozin administration was associated with reductions in AUC0-∞ and Cmax of 19.4% and 36.4%, respectively. However, based on the analysis of the pharmacokinetic/pharmacodynamic findings on henagliflozin, this slight change may not have clinical significance. Mass balance of henagliflozin in humans was achieved with ∼75% of the administered dose recovered in excretions within 4 days after administration whether in the fasted or fed state. These findings suggest that henagliflozin tablets can be administered with or without food.

16.
Br J Nutr ; : 1-10, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34435555

RESUMO

Vitamin D, Ca and dairy products are negatively associated with colorectal cancer (CRC) incidence, but little is known of their influence on CRC survival. To investigate prediagnostic intakes of vitamin D, Ca and dairy products for their relevance to CRC prognosis, we analysed 504 CRC patients enrolled in the Newfoundland Colorectal Cancer Registry Cohort Study who were diagnosed for the first time with CRC between 1999 and 2003. Follow-up for mortality and cancer recurrence was through April 2010. Data on diet and lifestyle factors were gathered via a validated, semi-quantitative FFQ and a Personal History Questionnaire. Multivariate Cox models estimated hazard ratios (HR) and 95 % CI for the relationship of prediagnostic intakes of vitamin D, Ca and dairy products with all-cause mortality (overall survival, OS) and disease-free survival (DFS) among CRC patients. We found that prediagnostic Ca intake from foods, but not total Ca intake, was negatively associated with all-cause mortality (HR for Q2 v. Q1, 0·44; 95 % CI, 0·26, 0·75). An inverse relationship was also seen in a dose-response fashion for prediagnostic cheese intake (HR for Q4 v. Q1, 0·57, 95 % CI, 0·34, 0·95, Ptrend = 0·029). No evidence for modification by sex, physical activity, alcohol drinking and cigarette smoking was observed. In summary, high prediagnostic intakes of cheese and Ca from foods may be associated with increased survival among CRC patients. By manipulating diet, this study may contribute to the development of novel therapies that add to the armamentarium against CRC. Replication studies are required before any nutritional interventions are made available.

17.
Environ Int ; 156: 106772, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34425644

RESUMO

BACKGROUND: Exposure to polybrominated diphenyl ethers (PBDEs) may influence risk of developing post-menopausal breast cancer. Although mechanisms are poorly understood, epigenetic regulation of gene expression may play a role. OBJECTIVES: To identify DNA methylation (DNAm) changes associated with PBDE serum levels and test the association of these biomarkers with breast cancer risk. METHODS: We studied 397 healthy women (controls) and 133 women diagnosed with breast cancer (cases) between ages 40 and 58 years who participated in the California Teachers Study. PBDE levels were measured in blood. Infinium Human Methylation EPIC Bead Chips were used to measure DNAm. Using multivariable linear regression models, differentially methylated CpG sites (DMSs) and regions (DMRs) associated with serum PBDE levels were identified using controls. For top-ranked DMSs and DMRs, targeted next-generation bisulfite sequencing was used to measure DNAm for 133 invasive breast cancer cases and 301 age-matched controls. Conditional logistic regression was used to evaluate associations between DMSs and DMRs and breast cancer risk. RESULTS: We identified 15 DMSs and 10 DMRs statistically significantly associated with PBDE levels (FDR < 0.05). Methylation changes in a DMS at BMP8B and DMRs at TP53 and A2M-AS1 were statistically significantly (FDR < 0.05) associated with breast cancer risk. CONCLUSION: We show for the first time that serum PBDE levels are associated with differential methylation and that PBDE-associated DNAm changes in blood are associated with breast cancer risk.


Assuntos
Neoplasias da Mama , Éteres Difenil Halogenados , Adulto , Biomarcadores , Neoplasias da Mama/genética , Metilação de DNA , Epigênese Genética , Feminino , Éteres Difenil Halogenados/toxicidade , Humanos , Menopausa , Pessoa de Meia-Idade
18.
J Cardiothorac Surg ; 16(1): 233, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34391454

RESUMO

BACKGROUND: Atrial fibrillation (AF) is associated with adverse events after cardiac surgery. Multiple studies have reported that posterior pericardiotomy (PP) may be effective for preventing AF after coronary artery bypass grafting (CABG), but some conflicting results have been reported and the quality of evidence from previous meta-analyses has been limited. The present study aimed to systematically evaluate the safety and efficacy of PP for preventing AF after CABG in adults. METHODS: We conducted a quantitative meta-analysis of randomized controlled trials (RCTs) published before May 31, 2021. The primary outcome was AF after CABG under cardiopulmonary bypass. Secondary outcomes included early pericardial effusion, late pericardial effusion, pericardial tamponade, pleural effusion, length of hospital stay, length of intensive care unit (ICU) stay, pulmonary complications, intra-aortic balloon pump use, revision surgery for bleeding, and mortality. RESULTS: Ten RCTs with 1829 patients (910 in the PP group and 919 in the control group) were included in the current meta-analysis. The incidence of AF was 10.3% (94/910) in the PP group and 25.7% (236/919) in the control group. A random-effects model indicated that incidence of AF after CABG significantly lower in the PP group than in the control group (risk ratio = 0.45, 95% confidence interval 0.29-0.64, P < 0.0001). PP also effectively reduced the post-CABG occurrence of early pericardial effusion (RR = 0.28, 95% CI 0.15-0.50; P < 0.05), late pericardial effusion (RR = 0.06, 95% CI 0.02-0.16; P < 0.05), and pericardial tamponade (RR = 0.08, 95% CI 0.02-0.33; P < 0.05) as well as the length of ICU stay (weighted mean difference [WMD] = 0.91,95% CI 0.57-1.24; P < 0.05), while increasing the occurrence pleural effusion (RR = 1.51, 95% CI 1.19-1.92; P < 0.05). No significant differences length of hospital stay (WMD = - 0.45, 95% CI - 2.44 to 1.54, P = 0.66), pulmonary complications (RR = 0.99, 95% CI 0.71-1.39, P = 0.97), revision surgery for bleeding (RR = 0.84, 95% CI 0.43-1.63, P = 0.60), use of IABP (RR = 1, 95% CI 0.61-1.65, P = 1.0), or death (RR = 0.45, 95% CI 0.07-3.03, P = 0.41) were observed between the PP and control groups. CONCLUSIONS: PP may be a safe, effective, and economical method for preventing AF after CABG in adult patients.


Assuntos
Fibrilação Atrial , Derrame Pericárdico , Adulto , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Ponte de Artéria Coronária/efeitos adversos , Humanos , Masculino , Derrame Pericárdico/epidemiologia , Derrame Pericárdico/etiologia , Derrame Pericárdico/prevenção & controle , Pericardiectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Photodiagnosis Photodyn Ther ; 36: 102481, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34403826

RESUMO

BACKGROUND: To explore the association of cigarette smoking with retinal thickness and vascular structure in an elderly Chinese population. METHODS: This cross-sectional study enrolled employees and retirees aged over 50 years at Tianjin University of Sport from October 2020 to December 2020. Information on smoking status and lifestyle was obtained using a detailed questionnaire. All participants underwent full ophthalmic examination. OCTA image was acquired. Vascular and the thickness parameters in central fovea and peripapillary parameters were automatically calculated. Multiple linear regression analyses were utilized to assess the association of smoking with retinal thickness and vascular structure after controlling potential confounders. RESULTS: Compared with non-smoking adults, current smokers (ß=-36.78; P = 0.01) and ever smokers (ß=-35.45; P = 0.00) tended to have thinner macular fovea. Cigarettes daily, pack-years of smoking and CSI were negatively related to macular thickness (cigarettes daily: ß=-1.43; pack-years: ß=-14.73; CSI: ß=-14.70), while they were positively associated with the circumference (cigarettes daily: ß=0.03; pack-years: ß=0.30; CSI: ß=0.31) and the area of FAZ (cigarettes daily: ß=0.01; pack-years: ß=0.07). CONCLUSIONS: Cigarette smoking seems associated with decreased macular fovea thickness and elevated circumference and area of the FAZ compared to non-smokers. Our data add to evidence of smoking on retinal thickness and the microvascular system in the macular area.

20.
Protoplasma ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338853

RESUMO

The secretory ducts of Ferula ferulaeoides (Steud.) Korov. are the main tissue of synthesis, secretion, and accumulation of resin. The formation of secretory ducts is closely related to the harvest and quality of resin, but the lumen formation mode and corresponding mechanism have not been thoroughly studied. This study of F. ferulaeoides investigated the microstructure and ultrastructure of the secretory ducts from a developmental point of view. Stem samples were analyzed by light microscopy, transmission electron microscopy, and fluorescence microscopy. The data results showed (1) the walls of secretory cells were intact during the development of secretory ducts in F. ferulaeoides; (2) the plastids and endoplasmic reticulum of secretory cells participated in the synthesis of resin; (3) pectinase was involved in the degradation of the middle lamella; and (4) no features of programmed cell death during the formation of secretory ducts. The results suggested that the formation of F. ferulaeoides' secretory ducts was schizogenous, and pectinase was involved in its formation. These data may be beneficial to further explore the formation of secretory duct in other species of Ferula L. and the formation mechanism of schizogenous secretory structures.

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