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1.
Chemosphere ; 280: 130774, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33971412

RESUMO

ß-Cyclodextrin (ß-CD) is an inexpensive and reproducible material derived from corn starch. It is possible that tetrafluoroterephthalonitrile-crosslinked ß-cyclodextrin polymer (TFN-CD), a cheap but efficient adsorbent, could be a suitable binding agent for use in the passive sampling technique, diffusive gradients in thin-films (DGT). Herein, the TFN-CD binding gel was prepared and then evaluated as the binding phase of DGT to sample six endocrine disrupting chemicals (EDCs) in water. The TFN-CD dispersed uniformly in the binding gel due to its hydrophilicity. The quantitative recoveries (99.3%-106%) of EDCs from the TFN-CD binding gel could be conveniently achieved by ultrasonic extraction using 5 mL methanol for 10 min. Compared with the excellent HLB (hydrophilic-lipophilic-balanced resin) binding gel, the TFN-CD binding gel had comparable or even faster adsorption kinetics, although the equilibrium adsorption capacity was slightly lower. The effective adsorption capacities of TFN-CD-based DGT (TFN-CD-DGT) were roughly estimated to enable a 7-days deployment in EDC solution of 25.7-30.0 µg L-1. Studies of influencing factors showed that the ionic strength (0-0.5 M), pH (3.73-9.13), dissolved organic matter (0-20 mg L-1) and long-term storage (204 days) had negligible influence on the performance of TFN-CD-DGT. Finally, the TFN-CD-DGT was successfully used to record sudden increases in bulk concentrations during simulated discharge events in pond water. These results demonstrate that TFN-CD is a suitable binding agent for sampling of EDCs, and the low cost of TFN-CD could be conducive to the application of DGT in large-scale sampling.

2.
Cell Death Dis ; 12(5): 470, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976108

RESUMO

Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to cardiac fibrosis and heart failure (HF). Recent studies have demonstrated that EndMT is regulated by autophagy, and we previously showed suppression of excessive autophagy and alleviation of cardiac fibrosis in HF mice with inactivated receptor for advanced glycation end products (RAGE). Thus, we investigated whether reduced cardiac fibrosis due to RAGE knockout occurred by inhibiting EndMT mediated by excessive autophagy. We found a decrease in endothelial cells (CD31+/VE-Cadherin+) and an increase in cells co-expressing CD31 and α-smooth muscle actin (α-SMA, myofibroblast marker) at 8 weeks in heart tissue of mice subjected to transverse aortic constriction (TAC), which implied EndMT. Knockout RAGE decreased EndMT accompanied by decreased expression of autophagy-related proteins (LC3BII/I and Beclin 1), and alleviated cardiac fibrosis and improved cardiac function in TAC mice. Moreover, 3-methyladenine (3-MA) and chloroquine (CQ), inhibitors of autophagy, attenuated EndMT, and cardiac fibrosis in TAC mice. Importantly, EndMT induced by AGEs could be blocked by autophagy inhibitor in vivo and in vitro. These results suggested that AGEs/RAGE-autophagy-EndMT axis involved in the development of cardiac fibrosis and knockout RAGE ameliorated cardiac fibrosis through decreasing EndMT regulated by autophagy, which could be a promising therapeutic strategy for HF.

3.
Nat Commun ; 12(1): 2672, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976130

RESUMO

Most patients with triple negative breast cancer (TNBC) do not respond to anti-PD1/PDL1 immunotherapy, indicating the necessity to explore immune checkpoint targets. B7H3 is a highly glycosylated protein. However, the mechanisms of B7H3 glycosylation regulation and whether the sugar moiety contributes to immunosuppression are unclear. Here, we identify aberrant B7H3 glycosylation and show that N-glycosylation of B7H3 at NXT motif sites is responsible for its protein stability and immunosuppression in TNBC tumors. The fucosyltransferase FUT8 catalyzes B7H3 core fucosylation at N-glycans to maintain its high expression. Knockdown of FUT8 rescues glycosylated B7H3-mediated immunosuppressive function in TNBC cells. Abnormal B7H3 glycosylation mediated by FUT8 overexpression can be physiologically important and clinically relevant in patients with TNBC. Notably, the combination of core fucosylation inhibitor 2F-Fuc and anti-PDL1 results in enhanced therapeutic efficacy in B7H3-positive TNBC tumors. These findings suggest that targeting the FUT8-B7H3 axis might be a promising strategy for improving anti-tumor immune responses in patients with TNBC.

4.
Ann Palliat Med ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33977742

RESUMO

BACKGROUND: An ECCOPG (Eastern China Cooperative Oncology Pharmacy Group) funded study was designed to compare the effect of 3 mg versus 6 mg pegfilgrastim for primary prevention of febrile neutropenia (FN) in Chinese breast cancer patients retrospectively. METHODS: Patients undergoing a docetaxel and cyclophosphamide chemotherapy regimen, followed by pegfilgrastim, for primary prevention during 2018 and 2020 were retrospectively enrolled in the present study. The patients were divided into 2 groups according to the dose of pegfilgrastim. The incidence of severe neutropenia (absolute neutrophil count <0.5×109 /L), incidence of FN, and recovery time were calculated to compare the efficacy of different groups. P<0.05 was considered statistically significant. RESULTS: A total of 295 patients were enrolled, 150 in the 3 mg pegfilgrastim group and 145 in the 6 mg pegfilgrastim group. No significant differences were found in the incidence of severe neutropenia (3 vs. 6 mg, 39.3% vs. 34.5%, P=0.401) and the incidence of FN (3 vs. 6 mg, 7.3% vs. 8.3%, P=0.830). Median recovery time was 2 days for both groups (P=0.485). CONCLUSIONS: 3 mg pegfilgrastim may be effective and safe for Chinese breast cancer patients as the primary prevention for FN. Prospective studies are needed to further confirm the prophylactic effect of 3 mg pegfilgrastim.

5.
Sci Total Environ ; 785: 147185, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33933763

RESUMO

Corpse degradation may release amounts of hazardous materials (e.g., cadaverine, putrescine and ammonia) into surrounding areas, which deteriorate environments and result in nitrogen contamination. Nitrate or nitrite can be reduced to nitrogen gas by denitrifying bacteria, thus alleviating nitrogen contamination and purifying aquatic environments. However, the reaction of nirS-encoding denitrifiers to carcass degradation is less studied. Therefore, water physiochemical analysis and high-throughput sequencing were applied to explore the successional pattern of nirS denitrifying communities in the Yellow River water and tap water during three stages of animal cadaver decay (submerged fresh, advanced floating decay as well as sunken remains) and relevant control group. Nitrate nitrogen (NO3-N) and ammonia nitrogen (NH4+-N) concentration in corpse groups were highly elevated compared with control groups. The dominant phylum for nirS denitrifying communities was Proteobacteria. Abundant denitrifying genera Paracoccus, Alicycliphilus and Diaphorobacter were detected, and these genera have been reported to participate in the degradation of organic pollutants. Particularly, nirS-type community structures were remarkably influenced by corpse decay and became similar with succession. Water total dissolved solids (TDS), salinity, conductivity (CON) and phosphate were primary impacting factors driving the community structures, but the effect of water type was almost negligible. Notably, denitrifying community assembly was dominated by deterministic processes rather than stochastic processes, and the relative importance of deterministic processes among most corpse groups was higher than that in control groups, indicating that environmental filtering regulates the denitrifying communities. Our results provide new insight into environmental purification for hazardous materials produced by corpse degradation, thereby providing valuable advice to environmental administration.

6.
Sci Total Environ ; 785: 147298, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33940401

RESUMO

Wetting-drying cycles typically result in a wide range of soil moistures and redox potentials (Eh) that significantly affect the soil microbial community. Although numerous studies have addressed the effects of soil moisture on soil microbial community structure and composition, the response of active microbes to the fluctuation in soil Eh is still largely unknown; this is especially true for the ecological roles of abundant and rare taxa. To explore the dynamics of active and total microbial communities in response to wetting-drying cycles, we conducted a microcosm experiment based on three wetting-drying cycles and 16S rRNA transcript (active) and 16S rRNA gene (total) amplicon sequencing. We found that both active and total microbial communities during three wetting-drying cycles were clustered according to the number of wetting-drying cycles (temporal factor) rather than soil moisture or Eh. Dynamics of the active microbial community, however, were redox dependent during the first wetting-drying cycle. In addition, rare taxa in the active microbial community exhibited more obvious differences than abundant ones during three wetting-drying cycles. Species turnover of abundant and rare taxa of total and active microbes, rather than species richness, explained the highest percentage of community variation. Rare taxa exhibited the most marked temporal turnover during three wetting-drying cycles. Members of Rhodospirillaceae were the major contributor to the resilience of abundant taxa of active microbes during the first wetting-drying cycle. Overall, these findings expand our current understanding of underlying assembly mechanisms of soil microbial communities responding to wetting-drying cycles.

7.
Biochem Biophys Res Commun ; 558: 154-160, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-33915329

RESUMO

Genistein, a naturally occurring phytoestrogen and a member of the large class of compounds known as isoflavones, exerts protective effects in several diseases. Recent studies indicate that genistein plays a critical role in controlling body weight, obesity-associated insulin resistance, and metabolic disorders, but its target organs in reversing obesity and related pathological conditions remain unclear. In this study, we showed that mice supplemented with 0.2% genistein in a high-fat diet for 12 weeks showed enhanced metabolic homeostasis, including reduced obesity, improved glucose uptake and insulin sensitivity, and alleviated hepatic steatosis. We also observed a beiging phenomenon in the white adipose tissue and reversal of brown adipose tissue whitening in these mice. These changes led to enhanced resistance to cold stress. Altogether, our data suggest that the improved metabolic profile in mice treated with genistein is likely a result of enhanced adipose tissue function.

8.
Reprod Biomed Online ; 42(5): 870-880, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33840620

RESUMO

RESEARCH QUESTION: This study aimed to identify small extracellular vesicle (sEV)-linked microRNAs (miRNA) specifically derived from intrafollicular cells in women with polycystic ovary syndrome (PCOS) and to investigate their biological functions. DESIGN: A total of 120 women were recruited from September 2017 to October 2018. To investigate miRNA profiles in sEV derived from follicular fluid and serum, 30 women with PCOS and 30 without PCOS were included for a miRNA microarray containing probes interrogating 2549 human miRNA. To study the expression levels of differentially expressed miRNA, sEV in follicular fluid obtained from another 30 PCOS and 30 non-PCOS patients were used for quantitative real-time polymerase chain reaction analysis. RESULTS: A total of 281 sEV-linked miRNA specifically derived from intrafollicular cells were identified, 179 of which were expressed in both the PCOS and non-PCOS groups. Twenty-six of the 179 intrafollicle-specific sEV-linked miRNA were predicted to target 1537 genes. Functional analysis suggested that these genes were involved in pathways related to folliculogenesis, including the MAPK, and PI3K-Akt signalling pathways. Quantitative real-time polymerase chain reaction analysis showed that the expression of seven intrafollicle-specific sEV-linked miRNA was significantly higher in follicular fluid-derived sEV in women with PCOS than in women without it. These miRNA and their corresponding target genes were identified as being involved in the MAPK signalling pathway and oocyte meiosis. CONCLUSIONS: The data suggest that the aberrantly expressed miRNA and their target genes might be associated with PCOS, providing novel insights into the molecular mechanisms underlying regulation of folliculogenesis and oocyte maturation in PCOS.

9.
Phys Chem Chem Phys ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33903862

RESUMO

It is currently technologically important to predict new two-dimensional (2D) ferromagnetic materials for next-generation information storage media. However, discovered 2D ferromagnetic materials are still rare. Here, we explored the fact that 2D transition metal borides are potential room-temperature 2D ferromagnetic materials. By performing first-principles calculations, we found that the CrB monolayer is a ferromagnetic (FM) metal, while the FeB monolayer is a typically antiferromagnetic (AFM) semiconductor. Interestingly, both CrB and FeB monolayers are FM metals with a moderate magnetic anisotropy energy by saturating with functional groups. Monte Carlo simulations show that the Curie temperature (Tc) of the CrB monolayer is about 520 K, which is further increased to 580 K and 570 K through -F and -OH chemical modification, while Tc is about 250 K, 275 K and 300 K for the FeBF, FeBO and FeBOH monolayer, respectively. Thus, the 2D transition metal borides have great potential applications in information storage devices.

10.
J Trace Elem Med Biol ; 66: 126755, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33838565

RESUMO

OBJECTIVE: We aimed to evaluate the association between baseline plasma zinc and the development of proteinuria as well as possible effect modifiers in hypertensive patients. METHODS: This is a subset of the China Stroke Primary Prevention Trial (CSPPT) Renal Sub-Study. In the CSPPT, participants were randomized to receive a daily oral dose of 1 tablet containing 10 mg enalapril and 0.8 mg folic acid or 1 tablet containing 10 mg enalapril only. A total of 783 participants with plasma zinc measurements and without proteinuria at baseline were included in the current study. The study outcome was the development of proteinuria during the follow-up, defined as a urine dipstick reading of trace or ≥1+ at the exit visit. RESULTS: During a median follow-up duration of 4.4 years, the development of proteinuria occurred in 93 (11.9 %) participants. There was an inverse relation of baseline plasma zinc with the development of proteinuria (per SD increment; OR, 0.74, 95 % CI: 0.55-0.99), p for trend of quartiles = 0.005. CONCLUSIONS: In Chinese hypertensive patients, there was a significant inverse association between baseline plasma zinc and the development of proteinuria, although plasma zinc remained in the reference range.

11.
Nitric Oxide ; 111-112: 14-30, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33839259

RESUMO

Hydrogen sulfide (H2S) is an important gaseous signal molecule which participates in various abiotic stress responses. However, the underlying mechanism of H2S associated salt tolerance remains elusive. In this study, sodium hydrosulfide (NaHS, donor of H2S) was used to investigate the protective role of H2S against salt stress at the biochemical and proteomic levels. Antioxidant activity and differentially expressed proteins (DEPs) of rice seedlings treated by NaCl or/and exogenous H2S were investigated by the methods of biochemical approaches and comparative proteomic analysis. The protein-protein interaction (PPI) analysis was used for understanding the interaction networks of stress responsive proteins. In addition, relative mRNA levels of eight selected identified DEPs were analyzed by quantitative real-time PCR. The result showed that H2S alleviated oxidative damage caused by salt stress in rice seedling. The activities of some antioxidant enzymes and glutathione metabolism were mediated by H2S under salt stress. Proteomics analyses demonstrated that NaHS regulated antioxidant related proteins abundances and affected related enzyme activities under salt stress. Proteins related to light reaction system (PsbQ domain protein, plastocyanin oxidoreductase iron-sulfur protein), Calvin cycle (phosphoglycerate kinase, sedoheptulose-1,7-bisphosphatase precursor, ribulose-1,5-bisphosphate carboxylase/oxygenase) and chlorophyll biosynthesis (glutamate-1-semialdehyde 2,1-aminomutase, coproporphyrinogen III oxidase) are important for NaHS against salt stress. ATP synthesis related proteins, malate dehydrogenase and 2, 3-bisphosphoglycerate-independent phosphoglycerate mutase were up-regulated by NaHS under salt stress. Protein metabolism related proteins and cell structure related proteins were recovered or up-regulated by NaHS under salt stress. The PPI analysis further unraveled a complicated regulation network among above biological processes to enhance the tolerance of rice seedling to salt stress under H2S treatment. Overall, our results demonstrated that H2S takes protective roles in salt tolerance by mitigating oxidative stress, recovering photosynthetic capacity, improving primary and energy metabolism, strengthening protein metabolism and consolidating cell structure in rice seedlings.

12.
BMC Cardiovasc Disord ; 21(1): 202, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882836

RESUMO

BACKGROUND: Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI. METHODS: This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained. RESULTS: A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P < 0.001). Besides, logistic analyses revealed that the increasing NT-proBNP level was robustly associated with an increased risk of in-hospital all-cause death (adjusted odds ratio (OR): 2.86, 95% confidence interval (CI) = 1.16-7.03, P = 0.022). NT-proBNP was able to predict the in-hospital all-cause death (area under the curve (AUC) = 0.888, 95% CI = 0.834-0.941, P < 0.001; cutoff: 1568 pg/ml). Moreover, as revealed by cumulative event analyses, a higher NT-proBNP level was significantly related to a higher long-term all-cause death rate compared with a lower NT-proBNP level (P < 0.0001). CONCLUSIONS: The increasing NT-proBNP level is significantly associated with the increased risks of in-hospital and long-term all-cause deaths among NSTE-ACS patients with MCAD undergoing PCI. Typically, NT-proBN P > 1568 pg/ml is related to the all-cause and in-hospital deaths.

13.
Curr Med Sci ; 41(2): 348-355, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33877553

RESUMO

Hyperthyroid heart disease (HHD) is one of the most severe complications of overt hyperthyroidism and increases the risk of mortality in affected patients. Early identification of patients at a higher risk of developing HHD can improve clinical outcomes through active surveillance and management. Connective tissue growth factor (CTGF), a secreted extracellular protein, plays a significant role in cardiac remodeling and dysfunction. We aimed to investigate the association between plasma CTGF level and the risk of HHD in this study. A total of 142 overt hyperthyroid patients without HHD and 99 patients with HHD were included. The plasma CTGF levels were measured using ELISA kits. Routine clinical medical data and echocardiography parameters were recorded for analysis. The plasma CTGF level was significantly higher in patients with HHD than in those without HHD (P=0.002). The plasma CTGF level was positively correlated with free triiodothyronin, tryrotropin receptor antibody, troponin I and lactate dehydrogenase levels and the left atrium diameters, right atrium diameters, and right ventricular end-diastolic diameters (all P<0.05). Logistic regression analysis showed that quartiles 3 and 4 of plasma CTGF levels were significantly associated with the increased risk of HHD (crude OR: 2.529; 95% CI: 1.188-5.387). However, after adjustment for the potentially confounding variables, quartile 4 alone was significantly associated with the higher risk of HHD relative to quartile 1. Hyperthyroid patients with HHD display higher plasma CTGF levels. Furthermore, CTGF is an independent risk factor for HHD. Therefore, the plasma CTGF level may be a potential biomarker for the risk of HHD.

14.
Acta Diabetol ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33909121

RESUMO

AIMS: The association between estimated glomerular filtration rate (eGFR) and the risk of diabetes remains uncertain. We aimed to examine the association between eGFR based on creatinine (eGFRcr), cystatin C (eGFRcys), or a combination of both (eGFRcr-cys) and new-onset diabetes, using data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative cohort study. METHODS: A total of 4,775 participants with pertinent measurements and without diabetes at baseline from CHARLS were included in the final analysis. The eGFR was calculated by creatinine, cystatin C or a combination of both using the Chronic Kidney Disease Epidemiology Collaboration equations. The study outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 126 mg/dL, random glucose ≥ 200 mg/dL, or HbA1c ≥ 6.5% (48 mmol/mol) at the exit visit. RESULTS: The mean age of the study population was 59.6 years. The mean values for the eGFRcr, eGFRcys, and eGFRcr-cys were 92.4, 78.9 and 85.9 mL/min/1.73m2, respectively. Over 4 years of follow-up, 612 (12.8%) participants experienced diabetes. Participants with lower eGFRcr-cys (< 60 mL/min/1.73m2) had a significantly higher risk of new-onset diabetes (adjusted OR, 1.46; 95%CI: 1.02, 2.09), compared to those with eGFRcr-cys ≥ 60 mL/min/1.73m2. However, there was no significant association between eGFRcr (< 60 vs. ≥ 60 mL/min/1.73m2; adjusted OR, 1.27; 95%CI: 0.75, 2.17) or eGFRcys (adjusted OR, 1.04; 95%CI: 0.80, 1.36) and new-onset diabetes. CONCLUSIONS: Lower eGFRcr-cys (< 60 mL/min/1.73m2), but not eGFRcr or eGFRcys, was significantly associated with an increased risk of new-onset diabetes in Chinese adults.

15.
J Am Chem Soc ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33887909

RESUMO

A bottom-up chemical synthesis of metal-organic frameworks (MOFs) permits significant structural diversity because of various combinations of metal centers and different organic linkers. However, fabrication generally complies with the classic hard and soft acids and bases (HSAB) theory. This restricts direct synthesis of desired MOFs with converse Lewis type of metal ions and ligands. Here we present a top-down strategy to break this limitation via the structural cleavage of MOFs to trigger a phase transition using a novel "molecular scalpel". A conventional CuBDC MOF (BDC = 1,4-benzenedicarboxylate) prepared from a hard acid (Cu2+) metal and a hard base ligand was chemically cleaved by l-ascorbic acid acting as chemical scalpel to fabricate a new Cu2BDC structure composed of a soft acid (Cu1+) and a hard base (BDC). Controlled phase transition was achieved by a series of redox steps to regulate the chemical state and coordination number of Cu ions, resulting in a significant change in chemical composition and catalytic activity. Mechanistic insights into structural cleavage and rearrangement are elaborated in detail. We show this novel strategy can be extended to general Cu-based MOFs and supramolecules for nanoscopic casting of unique architectures from existing ones.

16.
Nat Commun ; 12(1): 2002, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790299

RESUMO

Helicobacter pylori infection is a major etiological factor in gastric diseases. However, clinical antibiotic therapy for H. pylori is limited by continuously decreased therapeutic efficacy and side effects to symbiotic bacteria. Herein, we develop an in vivo activatable pH-responsive graphitic nanozyme, PtCo@Graphene (PtCo@G), for selective treatment of H. pylori. Such nanozymes can resist gastric acid corrosion, exhibit oxidase-like activity to stably generate reactive oxygen species only in acidic gastric milieu and demonstrate superior selective bactericidal property. C18-PEGn-Benzeneboronic acid molecules are modified on PtCo@G, improving its targeting capability. Under acidic gastric pH, graphitic nanozymes show notable bactericidal activity toward H. pylori, while no bacterial killing is observed under intestinal conditions. In mouse model, high antibacterial capability toward H. pylori and negligible side effects toward normal tissues and symbiotic bacteria are achieved. Graphitic nanozyme displays the desired enzyme-like activities at corresponding physiological sites and may address critical issues in clinical treatment of H. pylori infections.


Assuntos
Mucosa Gástrica/enzimologia , Grafite/química , Infecções por Helicobacter/enzimologia , Helicobacter pylori/metabolismo , Oxirredutases/metabolismo , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/uso terapêutico , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/terapia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Oxirredutases/química , Oxirredutases/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
17.
J Am Heart Assoc ; 10(8): e019922, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33843249

RESUMO

Background Antenatal intrauterine fetal hypoxia is a common pregnancy complication that has profound adverse effects on an individual's vascular health later in life. Pulmonary arteries are sensitive to hypoxia, but adverse effects of antenatal hypoxia on pulmonary vasoreactivities in the offspring remain unknown. This study aimed to determine the effects and related mechanisms of antenatal hypoxia on pulmonary artery functions in adult male offspring. Methods and Results Pregnant Sprague-Dawley rats were housed in a normoxic or hypoxic (10.5% O2) chamber from gestation days 10 to 20. Male offspring were euthanized at 16 weeks old (adult offspring). Pulmonary arteries were collected for vascular function, electrophysiology, target gene expression, and promoter methylation studies. In pulmonary artery rings, contractions to serotonin hydrochloride, angiotensin II, or phenylephrine were reduced in the antenatal hypoxic offspring, which resulted from inactivated L-type Ca2+ channels. In pulmonary artery smooth muscle cells, the basal whole-cell Ca2+ currents, as well as vasoconstrictor-induced Ca2+ transients were significantly reduced in antenatal hypoxic offspring. In addition, increased promoter methylations within L-type Ca2+ channel subunit alpha1 C were compatible with its reduced expressions. Conclusions This study indicated that antenatal hypoxia programmed long-lasting vascular hypocontractility in the male offspring that is linked to decreases of L-type Ca2+ channel subunit alpha1 C in the pulmonary arteries. Antenatal hypoxia resulted in pulmonary artery adverse outcomes in postnatal offspring, was strongly associated with reprogrammed L-type Ca2+ channel subunit alpha1 C expression via a DNA methylation-mediated epigenetic mechanism, advancing understanding toward the effect of antenatal hypoxia in early life on long-term vascular health.

18.
Genome Med ; 13(1): 57, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845891

RESUMO

BACKGROUND: Mutations in the DMD gene encoding dystrophin-a critical structural element in muscle cells-cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. METHODS: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46-54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. RESULTS: Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member ß-dystroglycan. CONCLUSIONS: We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

19.
J Surg Res ; 264: 553-561, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33864963

RESUMO

BACKGROUND: Postoperative nutritional therapy is of paramount importance for patients undergoing esophagectomy. The jejunostomy and nasoenteral tube are the popular routes for nutritional therapy. However, which one is the preferred route is unclear. This study aims to analyze the differences in safety and efficacy of the two routes for nutritional therapy. MATERIALS AND METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE (till September 17, 2020) were searched. The primary outcome was postoperative pneumonia. Secondary outcomes were the length of hospital stays (LOS), bowel obstruction, catheter dislocation, anastomotic leakage, overall postoperative complications, and postoperative albumin. Weighted mean differences (WMD) and odds ratios (OR) were calculated for statistical analysis. RESULTS: Ten studies involving a total of 1,531 patients in the jejunostomy group and 1,375 patients in the nasoenteral tube group were included. Compared with patients in the nasoenteral tube group, those in the jejunostomy group had a lower incidence of postoperative pneumonia (OR = 0.68, P < 0.001), shorter LOS (WMD = -0.85, P < 0.001), and lower risk of catheter dislocation (OR = 0.15, P = 0.001). There were no significant differences in the incidence of anastomotic leakage (OR = 0.84, P = 0.43), overall postoperative complications (OR = 0.87, P = 0.59), and postoperative albumin (WMD = -0.40, P = 0.24). However, patients in the jejunostomy group had a higher risk of bowel obstruction (OR = 8.42, P = 0.002). CONCLUSIONS: Jejunostomy for enteral nutrition showed superior outcomes in terms of postoperative pneumonia, LOS, and catheter dislocation. Jejunostomy may be the preferred enteral nutritional route following esophagectomy.

20.
Int Orthop ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33877408

RESUMO

PURPOSE: In the present study, we aimed to evaluate the clinical outcomes of surgical hip dislocation in patients with synovial chondromatosis (SC) of the hip. METHODS: Seven patients with primary SC of the hip treated with open synovectomy and removal of loose bodies by surgical hip dislocation from 2016 to 2019 were retrospectively reviewed. All patients had numerous and widespread loose bodies based on pre-operative images, including routine radiographs, CT, and MRI. The visual analog scale (VAS) score and Harris hip score (HHS) were collected and analyzed before and after surgery. The post-operative radiographs were reviewed to evaluate disease recurrence and osteoarthritis progression. RESULTS: The mean operative time was 61 minutes (range, 42-75 min). An average of 33 loose bodies in each patient (range, 16-67) was removed, and extra-articular pathology was found in one patient. Patients were followed up for a mean duration of 30 months (range, 18-42 months). The average VAS scores were decreased from 3.7 (range, 2-6) pre-operatively to 0.9 (range, 0-2) at the last follow-up, and the HHS was improved from 60.1 (range, 50-73) to 90.1 (range, 82-95). All results demonstrated significant improvements (P < 0.05). Post-operative radiographs showed no recurrence, osteoarthritis progression, or osteonecrosis of the femoral head in all hips. CONCLUSIONS: Surgical hip dislocation was a practical approach for managing both intra-articular and extra-articular pathologic lesions around the hip. It was an effective treatment for SC of the hip with short surgical time, good joint functions, a lower recurrence rate, and few complications.

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