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1.
Circulation ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31918577

RESUMO

Background: Diabetes exacerbates myocardial ischemia/reperfusion (MI/R) injury by incompletely understood mechanisms. Adipocyte dysfunction contributes to remote organ injury. However, the molecular mechanisms linking dysfunctional adipocytes to increased MI/R injury remain unidentified. The current study attempted to clarify whether and how small extracellular vesicles (sEV) may mediate pathological communication between diabetic adipocytes and cardiomyocytes, exacerbating MI/R injury. Methods: Adult male mice were fed a normal or a high fat diet for 12 weeks. sEV (from diabetic serum, diabetic adipocytes, or high glucose/high lipid (HG/HL)-challenged non-diabetic adipocytes) were injected intramyocardially distal of coronary ligation. Animals were subjected to MI/R 48 hours after injection. Results: Intramyocardial injection of diabetic serum sEV in the non-diabetic heart significantly exacerbated MI/R injury, as evidenced by poorer cardiac function recovery, larger infarct size, and greater cardiomyocyte apoptosis. Similarly, intramyocardial or systemic administration of diabetic adipocyte sEV or HG/HL-challenged non-diabetic adipocyte sEV significantly exacerbated MI/R injury. Diabetic epididymal fat transplantation significantly increased MI/R injury in non-diabetic mice, whereas administration of a sEV biogenesis inhibitor significantly mitigated MI/R injury in diabetic mice. Mechanistic investigation identified that miR-130b-3p is a common molecule significantly increased in diabetic serum sEV, diabetic adipocyte sEV, and HG/HL-challenged non-diabetic adipocyte sEV. Mature (but not primary) miR-130b-3p was significantly increased in the diabetic and non-diabetic heart subjected to diabetic sEV injection. Whereas intramyocardial injection of a miR-130b-3p mimic significantly exacerbated MI/R injury in non-diabetic mice, miR-130b-3p inhibitors significantly attenuated MI/R injury in diabetic mice. Molecular studies identified AMPKα1/α2, Birc6, and Ucp3 as direct downstream targets of miR-130b-3p. Overexpression of these molecules (particularly AMPKα2) reversed miR-130b-3p induced pro-apoptotic/cardiac harmful effect. Finally, miR-130b-3p levels were significantly increased in plasma sEV from type 2 diabetic patients. Incubation of cardiomyocytes with diabetic patient sEV significantly exacerbated ischemic injury, an effect blocked by miR-130b-3p inhibitor. Conclusions: We demonstrate for the first time that miR-130b-3p enrichment in dysfunctional adipocyte-derived sEV, and its suppression of multiple anti-apoptotic/cardioprotective molecules in cardiomyocytes, is a novel mechanism exacerbating MI/R injury in the diabetic heart. Targeting miR-130b-3p mediated pathological communication between dysfunctional adipocytes and cardiomyocytes may be a novel strategy attenuating diabetic exacerbation of MI/R injury.

2.
Sci Rep ; 10(1): 23, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913350

RESUMO

Diabetes mellitus (DM) significantly increases myocardial ischemia/reperfusion (MI/R) injury. During DM, cardioprotection induced by conventional pre-conditioning (PreCon) is decreased due to impaired AMP-activated protein kinase (AMPK) signaling. The current study investigated whether PreCon with inhaled anesthetic sevoflurane (SF-PreCon) remains cardioprotective during DM, and identified the involved mechanisms. Normal diet (ND) and high-fat diet (HFD)-induced DM mice were randomized into control and SF-PreCon (3 cycles of 15-minute period exposures to 2% sevoflurane) groups before MI/R. SF-PreCon markedly reduced MI/R injury in DM mice, as evidenced by improved cardiac function (increased LVEF and ±Dp/dt), decreased infarct size, and decreased apoptosis. To determine the relevant role of AMPK, the effect of SF-PreCon was determined in cardiac-specific AMPKα2 dominant negative expressing mice (AMPK-DN). SF-PreCon decreased MI/R injury in AMPK-DN mice. To explore the molecular mechanisms responsible for SF-PreCon mediated cardioprotection in DM mice, cell survival molecules were screened. Interestingly, in ND mice, SF-PreCon significantly reduced MI/R-induced activation of p38, a pro-death MAPK, without altering ERK and JNK. In DM and AMPK-DN mice, the inhibitory effect of SF-PreCon upon p38 activation was significantly blunted. However, SF-PreCon significantly increased phosphorylation of ERK1/2, a pro-survival MAPK in DM and AMPK-DN mice. We demonstrate that SF-PreCon protects the heart via AMPK-dependent inhibition of pro-death MAPK in ND mice. However, SF-PreCon exerts cardioprotective action via AMPK-independent activation of a pro-survival MAPK member in DM mice. SF-PreCon may be beneficial compared to conventional PreCon in diabetes or clinical scenarios in which AMPK signaling is impaired.

4.
Sci Rep ; 10(1): 878, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965030

RESUMO

The C1q complement/TNF-related protein superfamily (CTRPs) displays differential effects on the regulation of metabolic homeostasis, governing cardiovascular function. However, whether and how they may serve as predictor/pro-diagnosis factors for assessing the risks of coronary artery disease (CAD) remains controversial. Therefore, we performed a clinical study to elaborate on the implication of CTRPs (CTRP1, CTRP5, CTRP7, and CTRP15) in CAD. CTRP1 were significantly increased, whereas CTRP7 and CTRP15 levels were decreased in CAD patients compared to the non-CAD group. Significant differences in CTRP1 levels were discovered between the single- and triple-vascular-vessel lesion groups. ROC analysis revealed that CTRP7 and CTRP15 may serve as CAD markers, while CTRP1 may serve as a marker for the single-vessel lesion of CAD. CTRP1 and CTRP5 can serve as markers for the triple-vessel lesion. CTRP1 may serve as an independent risk predictor for triple-vessel lesion, whereas CTRP15 alteration may serve for a single-vessel lesion of CAD. CTRP1 may serve as a novel superior biomarker for diagnosis of severity of vessel-lesion of CAD patients. CTRP7, CTRP15 may serve as more suitable biomarker for the diagnosis of CAD patients, whereas CTRP5 may serve as an independent predictor for CAD. These findings suggest CTRPs may be the superior predictive factors for the vascular lesion of CAD and represent novel therapeutic targets against CAD.

5.
Antiviral Res ; 175: 104716, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981575

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is the most economically important infectious disease affecting the global swine industry, especially since vaccination has had limited impact on PRRSV prevention and control. In this study, the monoclonal antibody PR5nf1 (Mab-PR5nf1, IgM isotype) was shown to react with heterogeneous PRRSV isolates belonging to both PRRSV-1 and PRRSV-2 species. Pepsin digestion of Mab-PR5nf1 did not affect Mab binding to virions, as F(ab)2 fragments demonstrated the same reactivity as undigested Mab. Upon further investigation, Mab-PR5nf1 could neutralize all tested PRRSV isolates of both PRRSV-1 and PRRSV-2, suggesting it was a broadly neutralizing Mab against PRRSV. Interestingly, Mab-PR5nf1 appeared to recognize a specific virus epitope that required post-translational modification within the host cellular Golgi apparatus. Deglycosylation of PRRSV virions with PNGase F abolished Mab binding, suggesting that a novel Mab-binding epitope may exist that confers cross-protection against isolates of both PRRSV species. Additionally, immunization of mice with a cocktail of inactivated PRRSV virus and Mab-PR5nf1 enhanced cell-mediated immunity, as determined by IFN-γ ELIspot. In conclusion, this is the first report describing a novel Mab that recognizes a conserved epitope common to both PRRSV-1 and PRRSV-2 and provides valuable insights to guide future PRRSV vaccine development.

6.
Circ Res ; 126(2): 212-228, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31694459

RESUMO

RATIONALE: Obstructive sleep apnea-hypopnea syndrome, a sleep breathing disorder in which chronic intermittent hypoxia (CIH) is the primary pathology, is associated with multiple cardiovascular diseases. However, whether and how CIH may affect cardiac remodeling following myocardial infarction (MI) remains unknown. OBJECTIVE: To determine whether CIH exposure at different periods of MI may exacerbate post-MI heart failure and to identify the mechanisms underlying CIH-exacerbated post-MI remodeling. METHODS AND RESULTS: Adult male mice were subjected to MI (4 weeks) with and without CIH (4 or 8 weeks). CIH before MI (CIH+MI) had no significant effect on post-MI remodeling. However, double CIH exposure (CIH+MI+CIH) or CIH only during the MI period (MI+CIH) significantly exacerbated pathological remodeling and reduced survival rate. Mechanistically, CIH activated TGF-ß (tumor growth factor-ß)/Smad (homologs of both the Drosophila protein MAD and the C. elegans protein SMA) signaling and enhanced cardiac epithelial to mesenchymal transition, markedly increasing post-MI cardiac fibrosis. Transcriptome analysis revealed that, among 15 genes significantly downregulated (MI+CIH versus MI), Ctrp9 (a novel cardioprotective cardiokine) was one of the most significantly inhibited genes. Real-time polymerase chain reaction/Western analysis confirmed that cardiomyocyte CTRP9 expression was significantly reduced in MI+CIH mice. RNA-sequencing, real-time polymerase chain reaction, and dual-luciferase reporter assays identified that microRNA-214-3p is a novel Ctrp9 targeting miRNA. Its upregulation is responsible for Ctrp9 gene suppression in MI+CIH. Finally, AAV9 (adeno-associated virus 9)-mediated cardiac-specific CTRP9 overexpression or rCTRP9 (recombinated CTRP9) administration inhibited TGF-ß/Smad and Wnt/ß-catenin pathways, attenuated interstitial fibrosis, improved cardiac function, and enhanced survival rate in MI+CIH animals. CONCLUSIONS: This study provides the first evidence that MI+CIH upregulates miR-214-3p, suppresses cardiac CTRP9 (C1q tumor necrosis factor-related protein-9) expression, and exacerbates cardiac remodeling, suggesting that CTRP9 may be a novel therapeutic target against pathological remodeling in MI patients with obstructive sleep apnea-hypopnea syndrome.

8.
J Spec Pediatr Nurs ; : e12281, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31793223

RESUMO

OBJECTIVES: The objective of this study was to describe the occurrence of neonatal procedural pain and explore the factors that influence the frequency of painful procedures. DESIGN: A descriptive prospective epidemiologic study. SETTING: NICU at a general hospital in China. METHODS: A demographic and diagnosis or illness information questionnaire and an occurrence of procedural pain questionnaire specifically designed for this study were used to record the current status of neonatal procedural pain. The neonatal infant pain scale (NIPS) was used to measure pain intensity. A multiple linear regression model was used to explore the factors influencing the frequency of painful procedures. RESULTS: One hundred and twenty neonates experienced a total of 16,840 painful procedures. Each neonate was exposed to a median (IQR) of 66.5(27,154.75) painful procedures during hospitalization and a median (IQR) of 13(11, 19) painful procedures. All 27 different procedures were considered painful, and 70.37% (19/27) of these procedures caused severe pain. Overall, the mean NIPS score of the 27 procedures was 5.04 ± 1.52 with a range from 0 to 7. Respiratory support, age, and length of hospital stay were factors influencing the frequency of painful procedures. CONCLUSIONS: NICU neonates experience pain at a high frequency and intensity during hospitalization. Respiratory support, age, and length of hospital stay were factors influencing the frequency of painful procedures. Strategies are needed to bridge the gap between practice and the evidence-based guidelines.

9.
Sci Rep ; 9(1): 19084, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836775

RESUMO

Gastric cancer (GC) is one of the leading malignancies around the world. Identification of novel and efficient biomarkers for GC diagnosis and evaluation of therapeutic efficiency could improve the therapeutic strategy in future clinical application. This study aims to evaluate the levels of plasma thioredoxin reductase (TrxR) activity in GC patients to confirm its validity and efficacy in GC diagnosis and evaluation of therapeutic efficiency. 923 cases were enrolled in the current study. In the group of GC patients before clinical intervention, plasma TrxR activity [9.09 (7.96, 10.45) U/mL] was significantly higher than in healthy controls [3.69 (2.38, 5.32) U/mL]. The threshold of TrxR activity for GC diagnosis was set at 7.34 U/mL with a sensitivity of 85.5% and a specificity of 97.9%. In GC patients after chemotherapy, plasma TrxR activity was remarkably higher in patients with progressive disease or uncontrolled condition [10.07 (8.19, 11.02) U/mL] compared with patients with complete or partial response [7.12 (6.08, 8.37) U/mL] in response to chemotherapy. TrxR activity displayed the higher efficiency to distinguish between GC patients with two distinct clinical outcomes than carcinoembryonic antigen (CEA), cancer antigen 72-4 (CA72-4) and cancer antigen 19-9 (CA19-9). Moreover, combination of TrxR, CEA, CA72-4 and CA19-9 was demonstrated to be more effective in both GC diagnosis and evaluation of therapeutic efficiency than was each biomarker individually. Together, plasma TrxR activity was identified as a novel and efficient biomarker of GC, both in diagnosis and monitoring of therapeutic efficiency in response to chemotherapy.

10.
Medicine (Baltimore) ; 98(50): e18213, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852078

RESUMO

We aimed to investigate the association between excess body mass index (BMI) and papillary thyroid cancer (PTC) in an operative population, and the impact of higher BMI on clinicopathological aggressiveness of PTC.Charts of 10,844 consecutive patients with thyroid nodules undergoing partial or total thyroidectomy between 1993 and 2015 were reviewed. Patients diagnosed with PTC were stratified in 4 groups: BMI < 18.5 (underweight), 18.5 ≤ BMI < 24 (normal-weight), 24 ≤ BMI < 28 (overweight) and BMI ≥ 28(obese). The impacts of high BMI on prevalence and clinicopathological parameters of PTC were retrospectively analyzed in both univariate and multivariate binary logistic regression analysis.For every 5-unit increase in body mass, the odds of risk-adjusted malignance increased by 36.6%. The individuals who were obese and overweight were associated with high risk of thyroid cancer [odds ratio (OR)= 1.982, P < .001; OR= 1.377, P < .001; respectively] compared to normal weight patients, and this positive association was found in both genders. Obesity was independent predictors for tumors larger than 1 cm (OR = 1.562, P < .001) and multifocality (OR = 1.616, P < .001). However, there was no difference in cervical lymph node (LN) metastasis among BMI groups. Crude analysis showed BMI was associated with advanced tumor-node-metastasis (TNM) stage (relative risk, approximately 1.23 per 5 BMI units, P < .001), but this association disappeared after adjusting for confounding factors.Obesity was significantly associated with the risk of PTC in a large, operative population. Higher BMI was significantly associated with larger tumor size and multifocal tumor.


Assuntos
Índice de Massa Corporal , Obesidade/complicações , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Tireoidectomia/métodos , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/etiologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/cirurgia
11.
Nanomaterials (Basel) ; 9(11)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752211

RESUMO

P25 loaded few layered molybdenum disulfide (MoS2) nanosheets (P25@MoS2) are successfully synthesized through a facile one-step hydrothermal process. The bi-catalytic activities, i.e., photocatalytic and electrocatalytic activities, of the as-prepared nanomaterials have been investigated. For the as-prepared products, the photocatalytic performances were investigated by degrading simulated pollutant under sunlight irradiation, and the hydrogen evolution reaction evaluated the electrocatalytic performances. The results indicate that P25@MoS2 possesses excellent activities in both photocatalysis and electrocatalysis. The presence of MoS2 broadens the light absorption range of P25 and improves the separation and transformation efficiency of photogenerated carriers, thus improving its photocatalytic performance. The existence of P25 inhibits the aggregation of MoS2 to form more dispersed MoS2 nanosheets with only few layers increasing its active sites. Thereby, the electrocatalytic performance is heightened. The excellent multifunction makes the as-prepared P25@MoS2 a promising material in the fields of environment and energy.

12.
J Biosci Bioeng ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672431

RESUMO

CotA-laccases are potential enzymes that are widely used in decolorization of dyes and degradation of toxic substances. In this study, a novel CotA-laccase gene from Bacillus pumilus W3 was applied for rational design. After a series of site-directed genetic mutations, the mutant S208G/F227A showed a 5.1-fold higher catalytic efficiency (kcat/Km) than the wild-type CotA-laccase did. The optimal pH of S208G/F227A was 3.5 with ABTS as substrate. The residual activity of mutant S208G/F227A was more than 80% after incubated for 10 h at pH 7-11. Mutant S208G/F227A showed optimal temperature at 80°C with ABTS as substrate. The thermal stability of mutant laccase S208G/F227A was lower than that of wild-type CotA-laccase. This study showed that Gly208 and Ala227 play key roles in catalytic efficiency and it is possible to improve catalytic efficiency of CotA-laccase through site-directed mutagenesis.

13.
Emerg Microbes Infect ; 8(1): 1642-1657, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31711377

RESUMO

Diverse noroviruses infect humans and animals via the recognition of host-specific glycan ligands. Genogroup II (GII) noroviruses consist of human noroviruses (huNoVs) that generally bind histo-blood group antigens (HBGAs) as host factors and three porcine norovirus (porNoV) genotypes (GII.11/18/19) that form a genetic lineage lacking HBGA-binding ability. Thus, these GII porNoVs provide an excellent model to study norovirus evolution with host ligand specificity changes. Here we solved the crystal structures of a native GII.11 porNoV P protein and a closely-related GII.3 huNoV P protein complexed with an HBGA, focusing on the HBGA-binding sites (HBSs) compared with the previously known ones to understand the structural basis of the host ligand specificity change. We found that the GII.3 huNoV binds HBGAs via a conventional GII HBS that uses an arginine instead of the conserved aromatic residue for the required Van der Waals interaction, while the GII.11 porNoV HBS loses its HBGA-binding function because of two mutations (Q355/V451). A mutant that reversed the two mutated residues back to the conventional A355/Y451 restored the HBGA-binding function of the GII.11 porNoV P protein, which validated our observations. Similar mutations are also found in GII.19 porNoVs and a GII.19 P protein mutant with double reverse mutations restored the HBS function. This is the first reconstruction of a functional HBS based on one with new host specificity back to its parental one. These data shed light on the molecular basis of structural adaptation of the GII porNoVs to the pig hosts through mutations at their HBSs.

14.
Org Lett ; 21(23): 9506-9511, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31747294

RESUMO

Condition-controlled divergent oxidative coupling reactions between indole/tryptamine derivatives and ß-arylacrylic acids with the catalysis of copper(II) have been developed. Specifically, a formal Michael addition/dehydration sequence between indoles and ß-arylacrylic acids occurred in the presence of catalytic CuBr2 in CH3CN under air, thus affording highly functionalized 2,3-dihydro-1H-pyrrolo[1,2-a]indoles. In contrast, upon changing the oxidant to tBuOOH and the solvent to DCM, the reaction course switched to the unprecedented oxidative coupling/cyclization cascade to give the tetracyclic pyrrolo[2,3-b]indolines selectively.

15.
Animals (Basel) ; 9(10)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561614

RESUMO

The rates of mortality and involuntary culling of dairy calves and replacement heifers have great economic implications on the dairy cattle industry around the world. The main objectives of this study were: (1) to obtain population parameters of mortality and involuntary culling rates of dairy calves and replacement heifers; and, (2) to investigate the factors affecting mortality and involuntary culling rates in Chinese Holstein cattle. Two datasets containing records of birth, calving, and culling events from 142,833 Holstein cattle born between 1991 and 2018 were used in this study. The population parameters were obtained using dataset 1, which consisted of dairy calves and replacement heifers that died or were involuntarily culled. Three survival traits were defined in dataset 2, which consisted of females born from 1999 to 2018. A binomial logistic regression was used to analyze the risk factors on the survival traits. The mortality rate of dairy calves and replacement heifers from day 3 to 60, 61 to 365, and 366 to first calving was 5.5%, 7.4%, and 8.7%, and an unfavorable increasing trend was observed. Health events associated with digestive and respiratory or circulatory systems were the main death reasons. Herd-birth year, birth season, and dam parity had significant effects on survival traits. The results from this study will help farmers to better manage calves and replacement heifers and highlight the need to include survival traits in dairy calves and replacement heifers as part of national genetic evaluation schemes.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31480153

RESUMO

Objective: Caseins and fatty acids of milk are synthesized and secreted by the epithelial cells of the mammary gland. All-trans retinoic acid (ATRA), an active metabolite of vitamin A, has been shown to promote mammary development. This study was conducted to determine the effect of ATRA on casein synthesis and fatty acid composition in MAC-T cells. Methods: MAC-T cells were allowed to differentiate for 4 d, treated with ATRA (0, 1.0, 1.5, and 2.0 µM), and incubated for 3 d. We analyzed the fatty acid composition, the mRNA expression of casein and fatty acid synthesis-related genes, and the phosphorylation of casein synthesis-related proteins of MAC-T cells by gas chromatography, qPCR, and western blotting, respectively. Results: In MAC-T cells, ATRA increased the mRNA levels of αS1-casein and ß-casein, janus kinase 2 (JAK2) and E74-like factor 5 (ELF5) of the signal transducer and activator of transcription 5 ß (STAT5-ß) pathway, ribosomal protein S6 kinase beta-1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) of the mammalian target of rapamycin (mTOR) pathway, inhibited the mRNA expression of phosphoinositide 3-kinase (PI3K) and eukaryotic initiation factor 4E (eIF4E) of the mTOR pathway, and promoted the phosphorylation of STAT5-ß and S6K1 proteins. Additionally, ATRA increased the de novo synthesis of fatty acids, reduced the content of long-chain fatty acids, the ratio of monounsaturated fatty acids (MUFA) to saturated fatty acids (SFA), the ratio of polyunsaturated fatty acids (PUFA) to SFA, and the ratio of ω-6 to ω-3 PUFA. The mRNA levels of acetyl-CoA carboxylase 1, fatty acid synthase, lipoprotein lipase, stearoyl-CoA desaturase (SCD), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein 1 (SREBP1) were enhanced by ATRA. Conclusion: ATRA promotes the synthesis of casein by regulating JAK2/STAT5 pathway and downstream mTOR signaling pathway, and it improves the fatty acid composition of MAC-T cells by regulating SREBP1-related genes.

17.
J Cancer ; 10(18): 4278-4285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413747

RESUMO

Background: Chemotherapy impairs ovarian function in premenopausal breast cancer patients. Many breast cancer patients experience menopause earlier and therefore lose their reproductive abilities. The protective effect of gonadotropin-releasing hormone agonist (GnRha) upon the ovary is clearly apparent for hormone receptor (HR) negative patients, although the available data is not consistent for the patient body as a whole when considered regardless of HR status. It is also unknown whether levels of Anti-Mullerian Hormone (AMH) can reflect the influence of chemotherapy upon the ovary. Methods: We randomly assigned 98 premenopausal breast cancer patients regardless HR-positive or -negative to receive either standard chemotherapy with GnRHa (GnRHa group) or standard chemotherapy without GnRHa (control group). Our primary end point was ovarian failure rate (OVF) at 1 year. In addition, we observed the change of AMH level during chemotherapy and the association between AMH and OVF. Results: OVF was significantly lower (44.7%) in the GnRHa group than in the control group (80.6%; P=0.002). Median AMH levels were significantly higher before chemotherapy when compared to after 1/2cycles of chemotherapy, both in the GnRHa group (1.86ng/ml vs 0.12ng/ml; P=0.000) and in the control group (1.57ng/ml vs 0.10ng/ml; P=0.000). OVF was 91.3% in the AMH baseline level <1.1ng/ml group and 63.5% in the AMH baseline level >1.1ng/ml group (P=0.013). Conclusion: Data showed that GnRHa may have a protective effect on young breast cancer patients regardless of HR during chemotherapy. AMH could reflect changes of OVF during chemotherapy and predict OVF after chemotherapy.

18.
Animals (Basel) ; 9(8)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370306

RESUMO

This study investigated the effect of tannin sources on nutrient intake, digestibility, performance, nitrogen utilization, and blood parameters in lactating dairy cows. Four multiparous lactating Holstein cows were used in a balanced 4 × 4 Latin square design, with each period lasting 28 days. Cows were randomly assigned to one of four dietary treatments: Control diet (CON, a totally mixed ration without tannin supplements), control diet supplemented with 3% bayberry condensed tannins (BCT), control diet supplemented with 3% Acacia mangium condensed tannins (ACT), and control diet supplemented with 3% valonia hydrolyzed tannins (VHT). Dietary treatments did not significantly affect nutrient intake, milk yield or composition, microbial protein synthesis, nitrogen utilization efficiency, or plasma concentrations of glucose, non-esterified fatty acids, ß-hydroxybutyrate, total protein, and globulin, or the albumin-to-globulin ratio. Tannin supplements decreased the apparent total tract nutrient digestibility to varying degrees and significantly decreased the milk and blood urea nitrogen contents (p < 0.05). Tannin supplements altered nitrogen excretion routes in lactating dairy cows, and BCT significantly decreased the urinary nitrogen excretion (p = 0.04). Compared with the CON, ACT, and VHT diets, BCT yielded the highest nitrogen retention and nitrogen retention-to-digestible nitrogen ratio despite having a similar nitrogen utilization efficiency (p < 0.05). Bayberry condensed tannin supplementation may be a potential way to improve nitrogen utilization and reduce concerns regarding nitrogen excretion in dairy cows.

19.
Front Microbiol ; 10: 1803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447814

RESUMO

Inflammaging is well understood in the study of humans; however, it is rarely reported for dairy cows. To understand the changing pattern of the gut microbiota, inflammatory status and milk production performance during the aging process in cows, we grouped 180 cows according to their lactation period: L1 (n = 60, 1st lactation), L3 (n = 60, 3rd lactation), and L5+ (n = 60, at least 5th lactation) and analyzed their milk components and daily milk yields to evaluate the changing pattern of milk production. The microbiota was analyzed using high-throughput sequencing of amplicons of 16S rRNA, which also allowed us to predict the functions of microbes and then study the changing pattern of the ruminal and fecal microbiota. Serum cytokines, including TNF-α, IL-6, IL-10, and TGF-ß were measured to study the progress of inflammaging in the cows. We found that old cows (L5+) suffered from a long-term and low-level chronic inflammation, as indicated by significantly higher levels of inflammatory cytokines IL-10, TNF-α, and TGF-ß in the L5+ group (p < 0.001). We also observed a significant decrease in daily milk yield and milk lactose, as well as a significant increase in somatic cell score, among the cows in the L5+ group. For the gut microbiota, most of the genera belonging to Prevotellaceae and Lachnospiraceae, which had a higher abundance among cows of both the L1 and L3 groups (LEfSe, LDA > 2), showed a similar change pattern during the aging process, both in the rumen and in feces, and across the six farms. Beneficial bacteria, like Bacteroidaceae, Eubacterium, and Bifidobacterium, displayed lower abundance in the feces of the L5+ group (LEfSe, LDA > 2). Reconstruction of the fecal bacteria community indicated transformation of the fermenting pattern of older cows' (L5+) feces microbiota, with increased functions related the protein metabolism and fewer functions related to carbohydrate and lipid metabolism compared with those in L1 (p < 0.05). Finally, the connections among these changing patterns were revealed using redundancy analysis and network analysis. The results support the hypothesis of prolonging a cows' productive life and improve dairy cow milk productive performances by manipulating the gut microbiota.

20.
Circ J ; 83(8): 1726-1736, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31217391

RESUMO

BACKGROUND: Withaferin A (WFA), an anticancer constituent of the plant Withania somnifera, inhibits tumor growth in association with apoptosis induction. However, the potential role of WFA in the cardiovascular system is little-studied and controversial.Methods and Results:Two different doses of WFA were tested to determine their cardioprotective effects in myocardial ischemia/reperfusion (MI/R) injury through evaluation of cardiofunction in wild-type and AMP-activated protein kinase domain negative (AMPK-DN) gentransgenic mice. Surprisingly, cardioprotective effects (improved cardiac function and reduced infarct size) were observed with low-dose WFA (1 mg/kg) delivery but not high-dose (5 mg/kg). Mechanistically, low-dose WFA attenuated myocardial apoptosis. It decreased MI/R-induced activation of caspase 9, the indicator of the intrinsic mitochondrial pathway, but not caspase 8. It also upregulated the level of AMP-activated protein kinase (AMPK) phosphorylation and increased the MI/R inhibited ratio of Bcl2/Bax. In AMPK-deficient mice, WFA did not ameliorate MI/R-induced cardiac dysfunction, attenuate infarct size, or restore the Bcl2/Bax (B-cell lymphoma2/Mcl-2-like protein 4) ratio. CONCLUSIONS: These results demonstrated for the first time that low-dose WFA is cardioprotective via upregulation of the anti-apoptotic mitochondrial pathway in an AMPK-dependent manner.

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