Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.301
Filtrar
2.
BMC Pregnancy Childbirth ; 21(1): 622, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521386

RESUMO

BACKGROUND: Postpartum fatigue is the most common issue among postnatal women and it could not only seriously affect the health of mothers but also bring about adverse impacts on their offspring. This meta-analysis aims to synthesize nonpharmacological evidence and evaluate the effectiveness of interventions for reducing postpartum fatigue among puerperae. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, PsycINFO, CINAHL and ProQuest databases were searched for papers published from inception until June 2021. Grey literature was searched using OpenGrey. Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) evaluating nonpharmacological interventions conducted during 0 ~ 78 weeks postpartum for fatigue reduction were eligible for inclusion. The methodological quality of the included studies was independently assessed by two reviewers using the Cochrane risk-of-bias tool and the risk of bias in nonrandomized studies of interventions. Cohen's kappa coefficient was used to measure inter-rater agreement. The meta-analysis was conducted using Review Manager 5.3. RESULTS: Seventeen published clinical trials matched the eligibility criteria and ten studies involving 1194 participants were included in this meta-analysis. The intervention start time varied from immediately postpartum care to 1 year after delivery, and duration ranged from 1 day to 3 months. The results revealed that exercise (SMD = - 1.74, 95% CI = -2.61 to - 0.88) and drinking tea (MD = - 3.12, 95% CI = -5.44 to - 0.80) resulted in significant improvements in women's postpartum fatigue at postintervention. Drinking tea may have beneficial effects on depression (MD = - 2.89, 95% CI = -4.30 to - 1.49). Positive effects of psychoeducational interventions on postpartum fatigue or depression were not observed. Physical therapies including mother-infant skin-to-skin contact, taking warm showers and breathing lavender oil aroma were used for reducing postpartum fatigue. No significant risk of publication bias was found. Small number of included studies and sample sizes, not time-matched conditions of control groups, high heterogeneity and the risk of bias within the included studies were the main limitations of our review. CONCLUSIONS: This review provides evidence that exercise and drinking tea may be effective nonpharmacological interventions for relieving postpartum fatigue. More effective and targeted exercise programs need to be further studied. Rigorous RCTs of drinking tea are needed. Caution is required when interpreting the findings due to the limitations of our study. Further studies are still needed to validate our findings and increase confidence in the results.

3.
Environ Res ; 204(Pt A): 111919, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34480949

RESUMO

In this study, we investigated a highly efficient adsorbent that can be recycled from the soil. Walnut shells were used as raw materials to prepare original ecological biochar (OBC), illite modified biochar (IBC), FeCl3 modified biochar (magnetic biochar; MBC), and illite and FeCl3 modified biochar (IMBC), which were tested as low-cost adsorbents. The agents were used to remove metolachlor (MET) from soil. Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, magnetic sensitivity curve analysis, and a series of adsorption experiments were conducted to study the interaction between illite and MBC, and the effect on MET adsorption. Compared with OBC, IMBC had more adsorption sites on the surface. IMBC improved the hole filling effect during the adsorption process. IMBC had more oxygen-containing functional groups and it performed better at removing organic matter through π-π interactions. According to the Langmuir model, the Q0 values for IBC, MBC, and IMBC were 91.74 mg g-1, 107.53 mg g-1, and 129.87 mg g-1, respectively, which were significantly higher than that for OBC (72.99 mg g-1). The response surface model was used to explore the optimal adsorption conditions for IMBC. After three regeneration cycles, the MET adsorption rate with IMBC was still 81.38% and the MET recovery rate was 98.12%. Therefore, IMBC was characterized as an adsorbent with high efficiency, low cost, and good recyclability. In addition, we propose a suitable agricultural system for recovering MBC on site in the field.

4.
Int J Oral Sci ; 13(1): 29, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34493701

RESUMO

The use of traditional finite element method (FEM) in occlusal stress analysis is limited due to the complexity of musculature simulation. The present purpose was to develop a displacement boundary condition (DBC)-FEM, which evaded the muscle factor, to predict the dynamic occlusal stress. The geometry of the DBC-FEM was developed based on the scanned plastic casts obtained from a volunteer. The electrognathographic and video recorded jaw positional messages were adopted to analyze the dynamic occlusal stress. The volunteer exhibited asymmetrical lateral movements, so that the occlusal stress was further analyzed by using the parameters obtained from the right-side eccentric movement, which was 6.9 mm long, in the stress task of the left-side eccentric movement, which was 4.1 mm long. Further, virtual occlusion modification was performed by using the carving tool software aiming to improve the occlusal morphology at the loading sites. T-Scan Occlusal System was used as a control of the in vivo detection for the location and strength of the occlusal contacts. Data obtained from the calculation using the present developed DBC-FEM indicated that the stress distribution on the dental surface changed dynamically with the occlusal contacts. Consistent with the T-Scan recordings, the right-side molars always showed contacts and higher levels of stress. Replacing the left-side eccentric movement trace by the right-side one enhanced the simulated stress on the right-side molars while modification of the right-side molars reduced the simulated stress. The present DBC-FEM offers a creative approach for pragmatic occlusion stress prediction.

5.
Pharm Biol ; 59(1): 1256-1259, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34517743

RESUMO

CONTEXT: Pachymic acid and bavachin are commonly used drugs in the therapy of lung cancer. OBJECTIVE: The co-administration of pachymic acid and bavachin was investigated to evaluate their potential drug-drug interaction. MATERIALS AND METHODS: The pharmacokinetics of bavachin (10 mg/kg) was studied in male Sprague-Dawley (SD) rats in the presence of pachymic acid (5 mg/kg) (n = 6). The rats without pre-treatment of pachymic acid were set as the control and the pre-treatment of pachymic acid was conducted for 7 days before the administration of bavachin. The effect of pachymic acid on the activity of CYP2C9 was also estimated in rat liver microsomes with corresponding probe substrates. RESULTS: Pachymic acid influenced the pharmacokinetic profile of bavachin with the increased AUC (32.82 ± 4.61 vs. 19.43 ± 3.26 µg/L/h), the prolonged t1/2 (3.21 ± 0.65 vs. 2.32 ± 0.28 h), and the decreased CLz/F (307.25 ± 44.35 vs. 523.81 ± 88.67 L/h/kg) in vivo. The metabolic stability of bavachin was enhanced by pachymic acid and the transport of bavachin was inhibited by pachymic acid. Pachymic acid was found to inhibit the activity of CYP2C9 with the IC50 of 21.25 µM as well as the activity of P-gp. DISCUSSION AND CONCLUSION: The interaction between pachymic acid and bavachin results from the inhibition of CYP2C9 and P-gp. The dose of bavachin should be adjusted when combining with pachymic acid. The study design can be generalized to a broader study population with adjustment in the dose.

6.
Cell Death Dis ; 12(9): 845, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518524

RESUMO

Tumor cells require high levels of cholesterol for membrane biogenesis for rapid proliferation during development. Beyond the acquired cholesterol from low-density lipoprotein (LDL) taken up from circulation, tumor cells can also biosynthesize cholesterol. The molecular mechanism underlying cholesterol anabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are unclear. Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated in various cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we identified that LPCAT1 is highly expressed in ESCC and that LPCAT1 reprograms cholesterol metabolism in ESCC. LPCAT1 expression was negatively correlated with patient prognosis. Cholesterol synthesis in ESCC cells was significantly inhibited following LPCAT1 knockdown; cell proliferation, invasion, and migration were significantly reduced, along with the growth of xenograft subcutaneous tumors. LPCAT1 could regulate the expression of the cholesterol synthesis enzyme, SQLE, by promoting the activation of PI3K, thereby regulating the entry of SP1/SREBPF2 into the nucleus. LPCAT1 also activates EGFR leading to the downregulation of INSIG-1 expression, facilitating the entry of SREBP-1 into the nucleus to promote cholesterol synthesis. Taken together, LPCAT1 reprograms tumor cell cholesterol metabolism in ESCC and can be used as a potential treatment target against ESCC.

7.
Nat Commun ; 12(1): 5392, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518529

RESUMO

Across a range of creative domains, individual careers are characterized by hot streaks, which are bursts of high-impact works clustered together in close succession. Yet it remains unclear if there are any regularities underlying the beginning of hot streaks. Here, we analyze career histories of artists, film directors, and scientists, and develop deep learning and network science methods to build high-dimensional representations of their creative outputs. We find that across all three domains, individuals tend to explore diverse styles or topics before their hot streak, but become notably more focused after the hot streak begins. Crucially, hot streaks appear to be associated with neither exploration nor exploitation behavior in isolation, but a particular sequence of exploration followed by exploitation, where the transition from exploration to exploitation closely traces the onset of a hot streak. Overall, these results may have implications for identifying and nurturing talents across a wide range of creative domains.

8.
Food Res Int ; 148: 110583, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34507729

RESUMO

Recently protein has gained eminence due to awareness and demand for healthy food. Potato proteins are extracted from potato fruit juice and industrial potato waste; its nutritional and functional values have been found more significant than other vegetables and cereal proteins. Potato proteins can be easily extracted by various separation techniques, including an ion exchange (IEX) and expanded bed adsorption (EBA), and their functional properties can be modified for desire purposes. It contains many essential amino acids necessary for the human body, with an amino acid score (AAS) of 65%. Recent research on potato proteins resulted in several descriptions of new technologies to produce food-grade potato protein. It has recently drawn more attention as a protein source for human consumption, especially as an allergy free protein source and selective activity against cancer cells. Growing shreds of evidence have highlighted that potato protein can be used in many upcoming nutraceuticals and allergy-free food products. Therefore it is gaining more attention from nutritionists and food scientists. This review has summarized the recent knowledge on the nutritional and functional aspects of potato proteins, especially its non-allergic properties, enhancement in functional properties, and possible future-based products.

9.
Pediatr Dermatol ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514630

RESUMO

BACKGROUND/OBJECTIVES: Laryngo-onycho-cutaneous syndrome (LOC) is a rare subtype of junctional epidermolysis bullosa (JEB), featuring aberrant granulation tissue formation in the skin, larynx, and eyes. So far, three mutations including the specific (founder) mutation in exon 39 of LAMA3 (c.151dup) have been identified, but sparse data exists regarding the natural history, the genotype-phenotype correlation, and its differentiation from other JEB types. METHODS: We reviewed our pediatric EB database to identify English children with clinical and genetically diagnosed LOC within the last 15 years. Their demographic, clinical, and laboratory data were examined. We searched three databases for case reports of LOC between January 1986 and November 2020 and extracted clinical and molecular details. RESULTS: We identified 6 LOC patients, all female (mean age 5.4 years). Periungual hypergranulation and skin fragility were the earliest presenting signs (0-3 months), followed by laryngeal stenosis, symblepharon (mean onset 10.7 and 11.8 months, respectively), and dental abnormalities. Five children developed anemia at an average of 19.2 months. We identified 22 published studies in English with 31 cases. CONCLUSIONS: This study delineates the disease course of LOC and highlights the overlap with some forms of JEB. Classical signs/symptoms including anemia appear early in life. Genetic analysis revealed three new LOC-associated variants and underscores the finding that interpretation of skin immunolabeling and molecular diagnostics can be challenging. We provide recommendations on management of this complex syndrome.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34486152

RESUMO

OBJECTIVE: Measurements of plasma free metanephrines (MNs), including MN and normetanephrine, provide high sensitivity and specificity for the diagnosis of pheochromocytoma and paraganglioma (PPGL). 3-Methoxytyramine (3-MT) and chromogranin A (CgA) may allow the detection of dopamine-producing or biochemically silent PPGL. The aim of this study was to evaluate whether measurements of plasma 3-MT or CgA as a supplement of plasma MNs offer a better diagnostic strategy for initial testing of PPGL. PATIENTS AND DESIGN: We enroled 125 patients who underwent surgery from 2015 to 2016 for our study and identified 33 patients with PPGL and 92 patients with non-PPGL masses. MEASUREMENT: The levels of plasma free MNs and 3-MT were measured for all 125 patients using liquid chromatography-tandem mass spectrometry. Plasma CgA concentrations were determined using a radioimmunoassay. To evaluate the diagnostic performance of plasma free MNs, 3-MT and CgA, sensitivity and specificity were determined, and receiver operating characteristic curves were constructed. RESULTS: We found that combining 3-MT and MNs increased the diagnostic sensitivity from 93.9% (95% confidence interval [CI]: 78.4%-98.9%) to 97.0% (95% CI: 82.5%-99.8%). In contrast, addition of plasma CgA test reduced the diagnostic specificity significantly from 91.3% (95% CI: 83.1%-95.9%) to 75.0% (95% CI: 64.7%-83.2%). CONCLUSION: Here, we demonstrated that 3-MT represents a valuable supplementary test to plasma MNs, which can further enhance the sensitivity of the assay, while plasma CgA added no additional diagnostic value to MNs due to the lowered diagnostic specificity.

11.
Chemistry ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476846

RESUMO

Today, the threat of pathogenic bacterial infection worldwide that leads to the increase of mortality rate strongly demands the development of new antibacterial agents that can kill bacteria quickly and effectively. Although there are a lot of antibacterial agents that have been developed so far, few studies on the antibacterial ability of SnS have been investigated at 808 nm laser. Here, we synthesized SnS nanosheets with strong near-infrared absorption performance and excellent antibacterial performance via a simple hydrothermal synthesis route. The as-prepared SnS nanosheets showed excellent photothermal conversion efficiency (38.7%), photodynamic performance, and photostability, and at the same time 99.98% and 99.7% sterilization effect against Gram-negative Escherichia coli ( E. coli ) and Gram-positive Bacillus subtilis ( B. subtilis ) under near-infrared irradiation (808 nm, 1.5 W / cm 2 ). This study suggests that SnS nanosheets could be a promising candidate for antibacterial therapy owing to the synergetic effects of photothermal and photodynamic performance..

12.
J Appl Microbiol ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480826

RESUMO

AIMS: Brevilaterin B is a natural antimicrobial lipopeptide produced by Brevibacillus laterosporus S62-9. However, its antifungal spectrum and modes of action are still unclear. Herein, we investigated the detailed antifungal activity of brevilaterin B against 33 pathogenic fungi and the antifungal effects against two sensitive fungi in vitro and in vivo. METHODS AND RESULTS: Brevilaterin B exhibited inhibitory activity against 33 pathogenic fungi involved in plant disease and food spoilage at the minimum inhibitory concentrations (MIC) range of 16-128 µg mL-1 . The antifungal effects were further studied by Fusarium oxysporum and Penicillium chrysogenum. Both spore germination and mycelium growth were inhibited by brevilaterin B at sub-MIC. Transmission electron microscopy and fluorescent dye staining assays indicated brevilaterin B damaged cell integrity and induced apoptosis. In vivo tests, brevilaterin B inhibited the infection of F. oxysporum to Dendrobium officinale and P. chrysogenum to mandarin (Citrus reticulata) at 500 µg mL-1 , respectively. CONCLUSIONS: Brevilaterin B showed broad-spectrum antifungal activity against 33 pathogenic fungi. And its antifungal modes of action were proposed as damaging cell integrity and inducing cell apoptosis. The lipopeptide is promising to control F. oxysporum in the D. officinale and P. chrysogenum in the mandarin. SIGNIFICANCE AND IMPACT OF STUDY: The research provided insights into antifungal modes of action of brevilaterin B. The lipopeptide brevilaterin B is potential to be developed as a broad-spectrum antifungal agent for agricultural biocontrol and postharvest storage.

13.
Mater Sci Eng C Mater Biol Appl ; 128: 112310, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474861

RESUMO

Intervertebral disc (IVD) degeneration is a clinically disease that seriously endangers people's health. Tissue engineering provides a promising method to repair and regenerate the damaged IVD physiological function. Successfully tissue-engineered IVD scaffold should mimic the native IVD histological and macro structures. Here, 3D printing and electrospinning were combined to construct an artificial IVD composite scaffold. Poly lactide (PLA) was used to print the IVD frame structure, the oriented porous poly(l-lactide)/octa-armed polyhedral oligomeric silsesquioxanes (PLLA/POSS-(PLLA)8) fiber bundles simulated the annulus fibrosus (AF), and the gellan gum/poly (ethylene glycol) diacrylate (GG/PEGDA) double network hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs) simulated the nucleus pulposus (NP) structure. Morphological and mechanical tests showed that the structure and mechanical properties of the IVD scaffold were similar to that of the natural IVD. The compression modulus of the scaffold is about 10 MPa, which is comparable to natural IVD and provides good mechanical support for tissue repair and regeneration. At the same time, the porosity and mechanical properties of the scaffold can be regulated through the 3D model design. In the AF structure, the fiber bundles are oriented concentrically with each subsequent layer oriented 60° to the spinal column, and can withstand the tension generated during the deformation of the NP. In the NP structure, BMSCs were evenly distributed in the hydrogel and could maintain high cell viability. Animal experiment results demonstrated that the biomimetic artificial IVD scaffold could maintain the disc space and produce the new extracellular matrix. This engineered biomimetic IVD scaffold is a promising biomaterial for individualized IVD repair and regeneration.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Animais , Biomimética , Humanos , Degeneração do Disco Intervertebral/terapia , Impressão Tridimensional , Engenharia Tecidual , Tecidos Suporte
14.
Fitoterapia ; 154: 105027, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492330

RESUMO

Two novel kojic acid derivatives, kojicones A and B (1 and 2), along with the precursors kojic acid (3) and (2R,4R)-4-hydroxy-5-methoxy-2,4-dimethyl-2- [(2R)-2-methylbutyryloxy]-5-cyclohexen-1,3-dione (4), were isolated from a fungal strain Aspergillus versicolor. Their structures and absolute configurations were accurately confirmed by HRESIMS data, NMR analysis, and electronic circular dichroism (ECD) calculations. Kojicones A and B were the first examples of kojic acid adducts with cyclohexen-1,3-dione possessing unprecedented tricycle skeletons. Compounds 1-3 were found to have inhibition on the NO production of murine RAW 264.7 cells. They can also reduce the mRNA expression of four cytokines (IL-6, IL-1ß, TNF-α, and iNOS) and promote the expression of IL-4 at 20 µM. Moreover, kojic acid (3) could treat the DSS (dextran sulfate sodium)-induced colitis on mice with the effectiveness similar to that of the positive control. The results suggested that kojic acid and its derivatives could be a promising anti-inflammatory source for the medicinal and cosmetic industry.

15.
J Agric Food Chem ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499505

RESUMO

The present study investigated the potential of free radical grafting conjugation of whey protein isolate (WPI) and (-)-epigallocatechin-3-gallate (EGCG), followed by freeze-drying, for the safe delivery of probiotic Lactobacillus acidophilus (LA) upon digestion and in food systems. WPI-EGCG-LA microspheres presented higher encapsulation efficiency (97%) than native WPI-LA (70%) and maltodextrin (MD-LA 75%). The physicochemical characteristics of all microspheres, including moisture content, water activity, and hygroscopicity, were within the acceptable range for the stability of industrial powders. Scanning electron microscopy of WPI-EGCG-LA revealed a glass-like structure, with a smoother and less porous surface area than WPI-LA and MD-LA, as a result of the strong binding affinity between WPIs and EGCG. Particle sizes ranged from 438.4 to 453.3 µm. The structural stability of WPI-EGCG-LA was further confirmed by Fourier transform infrared spectra, which revealed some changes in the protein secondary structure. Thermogravimetric and differential scanning calorimetry analysis showed that WPI-EGCG conjugates had higher thermal stability than native WPIs and MD. Additionally, cells encapsulated in WPI-EGCG conjugates demonstrated higher in vitro survivability and surface hydrophobicity compared to free or WPI- and MD-encapsulated cells. Furthermore, WPI-EGCG-LA microspheres exerted enhanced in vitro antioxidant (78%) and antidiabetic (52%) activities. Finally, the WPI-EGCG conjugates remarkably improved probiotic viability (8.55 ± 0.1 log cfu/g) during 30 days of storage in an apple juice drink of pH (3.2 ± 0.01). Hence, the WPI-EGCG conjugate represents a propitious carrier to enhance probiotic functional properties upon digestion and during storage in low-pH food products.

16.
BMC Biol ; 19(1): 195, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496840

RESUMO

BACKGROUND: QconCATs are quantitative concatamers for proteomic applications that yield stoichiometric quantities of sets of stable isotope-labelled internal standards. However, changing a QconCAT design, for example, to replace poorly performing peptide standards has been a protracted process. RESULTS: We report a new approach to the assembly and construction of QconCATs, based on synthetic biology precepts of biobricks, making use of loop assembly to construct larger entities from individual biobricks. The basic building block (a Qbrick) is a segment of DNA that encodes two or more quantification peptides for a single protein, readily held in a repository as a library resource. These Qbricks are then assembled in a one tube ligation reaction that enforces the order of assembly, to yield short QconCATs that are useable for small quantification products. However, the DNA context of the short construct also allows a second cycle of loop assembly such that five different short QconCATs can be assembled into a longer QconCAT in a second, single tube ligation. From a library of Qbricks, a bespoke QconCAT can be assembled quickly and efficiently in a form suitable for expression and labelling in vivo or in vitro. CONCLUSIONS: We refer to this approach as the ALACAT strategy as it permits à la carte design of quantification standards. ALACAT methodology is a major gain in flexibility of QconCAT implementation as it supports rapid editing and improvement of QconCATs and permits, for example, substitution of one peptide by another.

17.
Ultrasonics ; 118: 106561, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500338

RESUMO

Angiogenesis involves the activation of endothelial cells (ECs). Low-intensity pulsed ultrasound (LIPUS), which delivers ultrasound waves at a low intensity, can induce the angiogenic potential of ECs. However, the underlying cellular mechanisms remain to be elucidated. In this study, the LIPUS parameters were 1.5 MHz pulsed frequency, 200 us pulse duration, 1.0 kHz repetition rate, and 30 mW/cm2 energy intensity. First, we evaluated the effects of LIPUS on the proliferation and angiogenic differentiation of the EC line EA.hy926. The results showed that LIPUS could induce cell proliferation, promote migration, and increase mRNA level inKDR and CD144.Also, the mRNA level and secretion of VEGF were enhanced. We then investigated the role of the AKT signaling pathway in this process. We observed that the expression of p-AKT was upregulated which means that the AKT signaling pathway could be activated by LIPUS, while inhibitor LY294002 of the AKT signaling pathway effectively blocked LIPUS-induced angiogenesis. Finally,we applied confocal Raman microscopy to track biomolecular changes in cells after LIPUS treatment. Spectral analysis showed DNA methylation changes. An Infinium Methylation assay suggested that399 sites were significantly different. After KEGG enrichment analysis, we found seven genes (IRS1, GNG7, COL4A1, FOXO3, COL4A2, CDK4 and EGF) which were closely related to AKT signaling pathway. We verified that AKT signaling pathway inhibition partially blocked LIPUS-induced DNA methylation changes. Ourstudy demonstrated that LIPUS couldpromote the proliferation and angiogenic differentiation of ECs via the AKT signaling pathway. LIPUS could also alter DNA methylation of ECs via the activation of AKT signal.

18.
Nature ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433965

RESUMO

Somatic mutations that accumulate in normal tissues are associated with ageing and disease1,2. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for in tissues from the oesophagus and cardia. Endogenous mutational processes with the SBS1 and SBS5 mutational signatures are ubiquitous among normal tissues, although they exhibit different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimetre resolution. In the oesophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometres were frequently seen, whereas in tissues such as the colon, rectum and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue microstructures. Our study depicts a body map of somatic mutations and clonal expansions from the same individual.

19.
J Biol Chem ; 297(3): 101049, 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34375640

RESUMO

Fused in sarcoma (FUS) encodes an RNA-binding protein with diverse roles in transcriptional activation and RNA splicing. While oncogenic fusions of FUS and transcription factor DNA-binding domains are associated with soft tissue sarcomas, dominant mutations in FUS can cause amyotrophic lateral sclerosis. FUS has also been implicated in genome maintenance. However, the underlying mechanisms of its actions in genome stability are unknown. Here, we applied gene editing, functional reconstitution, and integrated proteomics and transcriptomics to illuminate roles for FUS in DNA replication and repair. Consistent with a supportive role in DNA double-strand break repair, FUS-deficient cells exhibited subtle alterations in the recruitment and retention of double-strand break-associated factors, including 53BP1 and BRCA1. FUS-/- cells also exhibited reduced proliferative potential that correlated with reduced speed of replication fork progression, diminished loading of prereplication complexes, enhanced micronucleus formation, and attenuated expression and splicing of S-phase-associated genes. Finally, FUS-deficient cells exhibited genome-wide alterations in DNA replication timing that were reversed upon re-expression of FUS complementary DNA. We also showed that FUS-dependent replication domains were enriched in transcriptionally active chromatin and that FUS was required for the timely replication of transcriptionally active DNA. These findings suggest that alterations in DNA replication kinetics and programming contribute to genome instability and functional defects in FUS-deficient cells.

20.
J Orthop Surg Res ; 16(1): 525, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429140

RESUMO

BACKGROUND: Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats. METHODS: In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl's staining. The expressions of ß-CTX and osteocalcin were assessed by ELISA. RESULTS: It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker ß-CTX rather than osteocalcin increased significantly in FAC groups than OVX group. CONCLUSIONS: In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...