Patients with homozygous Phe508del cystic fibrosis were assigned to receive combination tezacaftor–ivacaftor or placebo for 24 weeks. The combination resulted in an FEV
1
that was 4 percentage points ...higher and a pulmonary-exacerbation rate that was 35% lower than with placebo.
Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components ...exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the “Fruits-Vegetables-Dairy” pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the “Puffed food-Bakery-Candy” pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the “Grains-Tubers-Legumes”. Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.
•The "Puffed food-Bakery-Candy" dietary pattern negatively affected IVF outcomes.•The "Fruits-Vegetables-Eggs" pattern improved normal fertilization and embryo quality.•Exposure to PM2.5 and its components was unfavorable for IVF success.•Animal organs and seafood mitigated the risk of early abortion associated with PM2.5.•"Grain-Tuber-Legume" ameliorated adverse effects of PM2.5 on embryo development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD). The ...glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.
Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled. Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry. The primary outcome measure was trough FEV1 at Week 12.
A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270). Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001). Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26. FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints. Transition dyspnoea index focal scores and St. George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and -2.81 (p = 0.004), respectively. NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo. NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.
Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.
ClinicalTrials.gov: NCT01005901.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are important mediators of intercellular communication and participate in numerous physiological and pathological processes ...in the body. This study aims to introduce the research status, analyze the research hotspots, and predict the development trend through bibliometric analysis of MSC-EVs.
Methods:
We searched all relevant literature on MSC-EVs from 2009 to 2021 in the Web of Science. R-bibliometrix, VOSviewer, and CiteSpace software were used to visualize the quantitative analysis of the published literature, including co-authorship, co-occurrence, citation, and co-citation, to provide objective presentation and predictions in the field.
Results:
A total of 1595 articles and reviews on MSC-EVs published between 2009 and 2021 were identified. The annual publication outputs increased at an exponential rate, reaching as high as 555 publications in 2021. China contributed the most publications (
n
= 899, 56.36%) and had the most citations (
n
= 24,210). The United States had the strongest intensity of cooperation in this field. Shanghai Jiao Tong University had the maximum number of publications (
n
= 79). In terms of the number of publications and co-citations, the journal of Stem cell research & therapy ranked first. Camussi G was the most productive and most cited author. The top three themes in the research area were cell biology, research experimental medicine, and biochemistry molecular biology. Keyword co-occurrence and co-citation clustering analysis revealed that studies of MSC-EVs covered cellular origin (bone marrow mesenchymal stem cell, adipose-derived mesenchymal stem cell), injurious diseases (spinal cord injury, acute lung injury, ischemia/reperfusion injury, acute kidney injury, traumatic brain injury), tumor (breast cancer, tumor microenvironment), biological processes (drug delivery system, angiogenesis, inflammation, proliferation, differentiation, senescence), and molecular mechanisms (signaling pathway, signal transduction, oxidative stress, VEGF, TGF β).
Conclusions:
Studies on MSC-EVs have shown a steep growth trend in recent years. Available studies mostly focused on the therapeutic effects and underlying mechanisms of MSC-EVs in aplastic diseases. Multidisciplinary integration is a development trend in this field, and senescence-related topics might be the focus of future research on MSC-EVs.
Intrauterine adhesion (IUA) is a reproductive dysfunction disease characterized by endometrial fibrosis, with limited therapeutic options and poor prognosis. Our previous studies confirmed that ...menstrual blood-derived stromal cells (MenSCs) effectively attenuated endometrial fibrosis in an animal model of IUA mainly through exosomes. This therapeutic effect can be enhanced by platelet-rich plasma (PRP), in which PDGFBB is an abundant growth factor. Therefore, we aimed to compare the effects of PRP and PDGFBB on the biological activities of MenSCs in vitro, and to further investigate the molecular mechanism of MenSCs-derived exosomes in alleviating endometrial fibrosis.
MenSCs were isolated for in vitro functional assays to examine the viability, migration, and stemness of MenSCs. Endometrial stromal cells (EndoSCs) were treated with 50 ug/ml of MenSCs-derived exosomes, obtained by differential ultracentrifugation extraction. The molecular mechanisms by which PDGFBB improves MenSCs and exosomes alleviate EndoSCs fibrosis were then explored using immunofluorescence, western blot, and co-immunoprecipitation.
Both 100 ng/ml PDGFBB and 10% activated PRP promoted the proliferation, increased the S phase of cell cycle, and inhibited apoptosis of MenSCs in vitro. Compared with PRP, PDGFBB significantly promoted MenSCs migration. All of these effects were inhibited by sorafenib, a PDGFR-β inhibitor. PRP and PDGFBB activated AKT/NF-κB signaling pathway in MenSCs and increased the expression of P65 and OCT4. Moreover, pretreatment of PDGFBB did not increase the secretion of MenSCs but significantly increased the anti-fibrosis effects of MenSCs-derived exosomes on IUA-EndoSCs. MenSCs-derived exosomes attenuated SMAD3 phosphorylation and increased YAP ubiquitination, which reduced the binding of YAP/SMAD3. Pretreatment with PDGFBB amplified this effect.
In summary, PDGFBB could improve the biological functions of MenSCs via AKT/NF-κB signaling pathway, including viability, migration, and stemness. Our results indicated that PDGFBB amplified MenSCs-derived exosomes to attenuate endometrial fibrosis by inhibiting YAP activity, revealing a novel mechanism by which PRP enhanced the ability of MenSCs to repair tissue injury and providing a potential option for improving stem cell efficacy in IUA.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Primary ovarian insufficiency (POI) is a heterogeneous disease with diverse clinical phenotypes and etiologies, which is defined as ovarian dysfunction under the age of 40 years. The global ...prevalence of POI is approximately about 1.1%, and it severely affects female fertility. Nevertheless, bibliometric analysis in this field is extremely limited. We aimed to visualize the research hotspots and trends of POI using bibliometric analysis and tried to predict the future development of this field.
The original articles regarding POI were culled from the Web of Science Core Collection. Countries, institutions, journals, authors, and keywords in this field were visually analyzed by employing CiteSpace software and Microsoft Excel 2021 software.
A total of 2,999 publications were included for further bibliometric analysis after screening the titles and abstracts stringently. The number of literature regarding POI significantly increased yearly. These publications come from 78 countries. The USA was dominant in the field of POI in terms of the number of publications (865), average citations per item (57.36), and
-index (112). The
is the most high-yield institution in this field with 351 publications.
ranked first with the highest number of publications (152), followed by
(138). According to the keyword cluster analysis from 2000 to 2021, the eight keyword clusters encountered frequently were apoptosis, osteoporosis, fertility preservation, mutation, fragile x syndrome, adrenal insufficiency, DNA repair, ovarian reserve. Keyword citation burst analysis revealed that whole-exome sequencing, ovarian tissue cryopreservation, and DNA repair had a citation burst until 2021.
Great progress has been made in POI research over the past 20 years, which is widely researched but unevenly developed in the world. In terms of influence, the United States may be in the lead. The research hotspots in POI are mainly pathogenesis and treatment, including genetic mutation, hormone therapy, fertility preservation, and stem cell transplantation.
Intrauterine adhesion (IUA) is a recurrent and refractory reproductive dysfunction disorder for which menstrual blood-derived stromal cells (MenSCs) might be a promising intervention. We reported ...that administration of MenSCs-derived exosomes (MenSCs-EXO) could achieve similar therapeutic effects to MenSCs transplantation, including alleviating endometrial fibrosis and improving fertility in IUA rats. The mass spectrometry sequencing result suggested that UBR4, a member of the proteasome family, was abundantly enriched in MenSCs-EXO. This study aimed to investigate the key role of UBR4 in MenSCs-EXO for the treatment of IUA and the specific molecular mechanism. UBR4 was lowly expressed in the endometrial stromal cells (EndoSCs) of IUA patients. MenSCs-EXO treatment could restore the morphology of IUA endometrium, reduce the extent of fibrosis, and promote endometrial and vascular proliferation. Knockdown of UBR4 in MenSCs did not affect the characteristics of exosomes but attenuated the therapeutic effect of exosomes. UBR4 in MenSCs-EXO could alleviate endometrial fibrosis by boosting YAP ubiquitination degradation and promoting YAP nuclear-cytoplasmic translocation. Moreover, P65 could bind to the UBR4 promoter region to transcriptionally promote the expression level of UBR4 in MenSCs. Our study clarified that MenSCs-EXO ameliorated endometrial fibrosis in IUA primarily by affecting YAP activity mediated through UBR4, while inflammatory signaling P65 may affect UBR4 expression in MenSCs to enhance MenSCs-EXO therapeutic effects. This revealed a novel mechanism for the treatment of IUA with MenSCs-EXO, proposing a potential option for the clinical treatment of endometrial injury.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Vitamin D plays an invaluable role in reproductive health, but vitamin D insufficiency and deficiency are generally common among couples of childbearing age and pregnant women. This study ...aimed to evaluate the evolution, development trend, and research hotspot of publications on vitamin D and reproductive health.
Methods
The literature on vitamin D and reproductive health between 2012 and 2021 was retrieved from the Web of Science Core Collection (WoSCC). We used VOSviewer and CiteSpace to analyze publication years, countries, institutions, journals, highly cited authors and publications, and co-occurrence and citation bursts of keywords.
Results
A total of 1,828 articles and reviews on vitamin D and reproductive health published between 2012 and 2021 were identified. The annual publication outputs showed steady growth, with the most publications (272) and citations (7,097) in 2021. The United States contributed the most publications (458) and had the highest
h
-index (58). In terms of the number of publications and
h
-index, the journal named Nutrients ranked first. Nutrition dietetics, obstetrics gynecology, and endocrinology metabolism were three well-represented disciplines in research on vitamin D and reproductive health. Hollis BW, Wagner CL, and Litonjua AA were the top three most productive authors in this field during the last decade. Apart from vitamin D, the five keywords with the most frequent occurrence were vitamin D deficiency, pregnancy, risk, vitamin D supplementation, and 25-hydroxyvitamin D. Keyword citation burst analysis revealed that low birth weight, adipose tissue, marker, and embryo had a citation burst lasting until 2021.
Conclusion
In conclusion, vitamin D has received continuous attention in the field of reproductive health, and there appears to have a higher level of research in North America. Multidisciplinary intersection contributed to the in-depth exploration in this field. And the effect of maternal vitamin D levels on fetal lipid metabolism and the prediction of fertility by vitamin D-related markers might be hotspots for the research.
By modifying immune cells, immunotherapy can activate immune response to establish long-term immune memory and prevent tumor recurrence. However, their effectiveness is largely constricted by the ...poor immunogenicity, immune escape, and immune tolerance of the tumor. This is related to the characteristics of the tumor itself, such as genome instability and mutation. The combination of various nanocarriers with tumor immunotherapy is beneficial for overcoming the shortcomings of traditional immunotherapy. Nanocarriers coated by cell membranes can extend blood circulation time, improve ability to evade immune clearance, and enhance targeting, thus significantly enhancing the efficacy of immunotherapy and showing great potential in tumor immunotherapy. This article reviews the application research progress of different types of cell membrane-modified nanocarriers in tumor immunotherapy, immunotherapy combination therapy, and tumor vaccines, and provides prospects for future research.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
Fireworks burning significantly degrades air quality over a short duration. The prohibition of fireworks burning (POFB) policy of 2016 and the restricted-hours fireworks burning (RHFB) policy of 2023 ...in Zhengzhou City provide an ideal opportunity to investigate the effects of such policies and of fireworks burning on air quality during the Spring Festival period. Based on air quality ground-based monitoring data and meteorological data for Zhengzhou City, the article analyzes the impact of the POFB policy and the RHFB policy on air quality. The results show that: (1) The ban on fireworks burning significantly affects Spring Festival air quality, with a decrease of 16.0% in the Air Quality Index (AQI) value in 2016 compared to 2015 and a 74.9% increase in 2023 compared to 2022. (2) From 2016 to 2022, the Spring Festival period witnessed a substantial decrease in average concentration of main pollutants, along with a delayed occurrence of peak concentrations, indicating a noticeable "peak-shaving" effect. However, in 2023, there was an increase in pollutant concentrations, volatility, and a significant surge in hourly concentration. (3) The POFB policy and RHFB policy notably impacted PM
and PM
, with a decrease of 16.1% and 23.6% in PM
and PM
concentrations, respectively, in 2016 compared to 2015, but an increase of 74.5% and 79.2%, respectively, in 2023 compared to 2022. (4) The contribution of fireworks burning to PM
concentrations significantly decreased during the fireworks burning period (FBP) in 2016 after the POFB policy and increased significantly in 2023 during FBP after the implementation of the RHFB policy. Unfavorable meteorological conditions will undoubtedly exacerbate air quality pollution caused by fireworks burning.
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