Publications by authors named "Li Yan"

14,835 Publications

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Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations.

J Hypertens 2022 Aug 9. Epub 2022 Aug 9.

Research Institute Alliance for the Promotion of Preventive Medicine, Mechelen.

Background: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes.

Method: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models.

Results: The 11 848 participants from 13 cohorts (age 53 ± 16 years, 50% men) were followed for up for 13.7 ± 6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated (r = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range.

Conclusion: This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age.
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http://dx.doi.org/10.1097/HJH.0000000000003258DOI Listing
August 2022

3-Arylcoumarin inhibits vascular calcification by inhibiting the generation of AGEs and anti-oxidative stress.

J Enzyme Inhib Med Chem 2022 Dec;37(1):2147-2157

Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

Objective: This work aims to screen drugs for preventing and treating vascular calcification. We screened a series of 3-arylcoumarins for the detection of vascular calcification-associated factors using human aortic vascular smooth muscle cells.

Results: We found that compounds and significantly inhibited alkaline phosphatase (ALP) activity similar to aminoguanidine hydrochloride (AGH) in a cellular model of AGEs-induced calcification. We also found that compounds and could significantly decrease the levels of factors such as AGEs, intracellular calcium ions, and total ROS in the calcified cell model. Further study indicates that compound could significantly inhibit the expression of P-ERK1/2, PKC, NF-κB, RAGE and OPN proteins and increased the expression of SM22-α and PPAR-γ proteins in the calcified cells.

Conclusion: We speculate that compound inhibits vascular calcification by inhibiting oxidative stress and inhibiting AGEs production, suggesting that 3-arylcoumarin derivatives are potential candidates for the treatment of vascular calcification.
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http://dx.doi.org/10.1080/14756366.2022.2109024DOI Listing
December 2022

A modified receptor model for source apportionment of sediment polycyclic aromatic hydrocarbons.

J Environ Manage 2022 Sep 1;318:115637. Epub 2022 Jul 1.

Collaborative Innovation Center of Sustainable Forestry, Nanjing Forestry University, Nanjing, Jiangsu, China.

Polycyclic aromatic hydrocarbons (PAHs) have become a serious threat to human health and ecological security due to their persistence and high toxicity. Lake sediments are in a relatively closed environment, so PAHs and other pollutants can be preserved for a long time. Accurate analysis of the sources of PAHs in sediments is an important prerequisite for PAH pollution control. However, the existing PAHs source resolution receptor model (the absolute principal component analysis - multilinear regression (APCA-MLR) and positive matrix factorization (PMF)) has many defects, such as great uncertainty in the process of matrix rotation. In this study, we collected sediment samples from Taihu Lake and tested their PAH content, and the existing receptor model was improved. High PAH contents were distributed in Meiliang Bay, Zhushan Bay, Gonghu Bay and areas close to the shore. "High-High" areas were distributed in Meiliang Bay, Gonghu Bay and areas close to the shore. "Low-Low" areas appeared in the central and southern parts of Taihu Lake. The results show that the improved positive matrix factorization partition computing (PMF-PC) model is significantly better than the APCA-MLR and PMF models in terms of both numerical simulation accuracy and the spatial distribution consistency of PAHs. The correlations (R) between the measured and simulated values of low-molecular-weight PAHs (L-PAHs), high-molecular-weight PAHs (H-PAHs) and PAHs were 0.992, 0.989 and 0.993, respectively. The contributions of biomass sources, coal combustion sources and petroleum sources to PAHs in Taihu Lake sediments reached 16.7%, 31.7% and 51.6%, respectively. Fossil fuel sources were mainly concentrated in areas near the shore, and the contribution was lower in areas far from the shore. Although the algorithm still needs to be improved, the PMF-PC model may become a useful tool for the source apportionment of PAHs in sediments.
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http://dx.doi.org/10.1016/j.jenvman.2022.115637DOI Listing
September 2022

Detection of Corneal Ectasia Using OCT Maps of Pachymetry and Posterior Surface Mean Curvature.

J Refract Surg 2022 Aug 1;38(8):502-510. Epub 2022 Aug 1.

Purpose: To quantify the abnormal corneal thinning and posterior surface steepening that is observed in keratoconus with an Ectasia Index.

Methods: Optical coherence tomography (OCT) was used to image the corneas of normal individuals and patients with varying stages of keratoconus (manifest, subclinical, and forme fruste). Maps of corneal pachymetry and posterior surface mean curvature were generated, and an Ectasia Index was calculated by multiplying Gaussian fits obtained from the two types of maps. Repeated five-fold cross-validation was used to evaluate the ability of the Ectasia Index to differentiate between normal and keratoconic eyes. The classification performance of the Ectasia Index was compared to minimum pachymetry and maximum posterior mean curvature.

Results: Thirty-two eyes from 16 normal individuals, 89 eyes from 63 patients with manifest keratoconus, 16 eyes from 15 patients with subclinical keratoconus, and 26 eyes from 26 patients with forme fruste keratoconus were included in the study. During cross-validation, 100% of the eyes with manifest (89 of 89) and subclinical (16 of 16) keratoconus were correctly classified by the Ectasia Index. The average classification accuracy for the forme fruste keratoconus group was 63 ± 21% (16.4 of 26). The specificity for the normal group was 91 ± 10% (29.1 of 32). The Ectasia Index had a higher sensitivity for keratoconus detection and similar specificity in comparison to minimum pachymetry and maximum posterior mean curvature.

Conclusions: The Ectasia Index could be a valuable additional metric for clinicians to consider when screening for keratoconus. .
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http://dx.doi.org/10.3928/1081597X-20220711-01DOI Listing
August 2022

ITGA5 and ITGB1 contribute to Sorafenib resistance by promoting vasculogenic mimicry formation in hepatocellular carcinoma.

Cancer Med 2022 Aug 10. Epub 2022 Aug 10.

Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

Background: Hepatocellular carcinoma (HCC) is labeled with high mortality and tolerance to chemotherapy. Sorafenib has been the first-line treatment option in HCC patients for past decades, while the therapeutic effect was limited in almost HCC patients.

Methods: In this study, we analyzed public omics data of HCC patients with different responses to Sorafenib treatment. To confirm the role of integrins A5 and B1 (ITGA5 and ITGB1) in Sorafenib resistance, we generated the Sorafenib-resistant (Sor-R) cell lines and cells overexpressing ITGA5 or ITGB1. Hypoxia level was measured using Hypoxy probe by flow cytometry, while vasculogenic mimicry was detected and quantified by CD31 and periodic acid schiff staining.

Results: Hypoxia was upregulated in non-responsive patients, accompanied with genes involved in encoding extracellular matrix components and angiogenesis such as ITGA5 and ITGB1. Sor-R hepatoma cell lines were constructed to measure expression and role of candidate genes. ITGA5 and ITGB1 were augmented in Sor-R cells. Upregulation of ITGA5 or ITGB1 reduced the sensitivity to Sorafenib in HepG2 and Huh7 cells, aggravated the hypoxic condition and resulted in formation of vascular mimicry.

Conclusions: These findings suggested that hypoxia associated vascular mimicry account for non-response to Sorafenib treatment in HCC patients. ITGA5 and ITGB1 may serve as effective predictors of HCC patients' outcome after Sorafenib treatment, which also provides a new target for HCC patients resistant to Sorafenib.
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http://dx.doi.org/10.1002/cam4.5110DOI Listing
August 2022

Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancer.

NPJ Breast Cancer 2022 Aug 9;8(1):92. Epub 2022 Aug 9.

Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.

Although the value of tumor-infiltrating lymphocytes is well known, the clinical relevance of an increased immune response, specifically in breast cancer, has not been investigated across large cohorts of patients using computational algorithms. Our hypothesis stated that an enhanced immune response is associated with an improvement in outcomes. To quantify the immune response, we utilized the allograft rejection score correlated with cytolytic activity and with all the other Hallmark immune-related gene sets. The score reflected the amount of infiltrating immune cells that correlated with the immune checkpoint molecule expressions, including CD4 and CD8 T cells, T helper type 1 (Th1) and type 2 (Th2) cells, M1 macrophages, B cells, and plasmacytoid dendritic cells (pDC). A high score was associated with high levels of intratumor heterogeneity, homologous recombination defects, mutation rate, histological grade, advanced stage, and lymph node metastasis. Breast malignancy with a high score enriched immune-related gene sets and pro-cancer-related gene sets, including epithelial-mesenchymal transition and KRAS pathway, in ER-positive/HER2-negative and triple-negative breast cancer (TNBC) groups. TNBC had the highest score compared to other subtypes, and was associated with better survival. In conclusion, we found that breast cancer with a high immune response is associated with aggressive cancer biology, but with better survival in TNBC.
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http://dx.doi.org/10.1038/s41523-022-00466-2DOI Listing
August 2022

Efficacy of binocular vision training and Fresnel press-on prism on children with esotropia and amblyopia.

Int Ophthalmol 2022 Aug 9. Epub 2022 Aug 9.

Department of Ophthalmology, Guiyang Maternal and Child Health Hospital, Guiyang, 550003, Guizhou, China.

Purpose: In the process of clinical diagnosis and treatment of amblyopia, we have found that the treatment time of this disease was significantly different among different patients. The purpose of this study was to compare the efficacy of binocular vision training (BVT) and Fresnel press-on prism (FPP) on children with esotropia combined with amblyopia.

Methods: From May 2015 to December 2018, a total of 101 children aged 3-9 years with esotropia and amblyopia who were in our hospital were enrolled in this randomized clinical trial. They were randomly divided into combined group (48 cases) and prism group (53 cases): the children in the prism group received FPP treatment, and those in the combined group received the combined treatment of BVT and FPP. The visual acuity, the binocular function and the strabismic therapeutic effects were compared between two groups.

Results: After treatment, the visual acuity in both groups was both significantly improved compared with that before treatment (P = 0.0079). The binocular-monocular function, including synoptophore visual function and the Titmus stereopsis, in both groups was significantly improved compared with those before treatment (P < 0.05), and it was more significant in the combined group compared with the prism group (P < 0.05). The cure rate of strabismus was 87.50% (42/48) and 30.19% (16/53) in the combined group and the prism group, respectively, and there was significant difference between groups (P = 0.0036). The cure time was shortened with the lower of the degree of esotropia.

Conclusion: BVT combined with FPP can effectively promote the recovery of binocular vision in children with esotropia combined with amblyopia, and some children can achieve complete cure of strabismus.
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http://dx.doi.org/10.1007/s10792-022-02461-9DOI Listing
August 2022

Effects of prenatal and infant daily exposure to pyrethroid pesticides on the language development of 2-year-old toddlers: a prospective cohort study in rural Yunnan, China.

Neurotoxicology 2022 Aug 6. Epub 2022 Aug 6.

School of Public Health, Kunming Medical University, Kunming, China. Electronic address:

Background: Prenatal and infant daily exposures to pyrethroid pesticides (PYRs), used in the elimination of harmful organisms in the family environment and agricultural activities, may have an impact on children's language development.

Objectives: To determine the impacts of prenatal and infant PYRs exposure on 2-year-old toddlers' language development.

Methods: From January 2016 to December 2018, women in the third trimester of pregnancy, in Yunnan rural area, China, were recruited, and the development of their newborns was observed from birth till the age of two. We examined three PYRs metabolites: 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-2,2dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) in urine samples collected from women in the third trimester of pregnancy and their infants of 6-8 months after birth, and assessed language development of 2-year-old toddlers by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Generalized linear models were used to analyze the impacts of exposure to PYRs on 2-year-old toddlers' language development.

Results: The median concentrations of 3PBA, 4F3PBA and DBCA creatinine-adjusted were 0.21, 0.19, and 0.15μg/g in pregnancy, and 0.25, 0.72, and
Conclusion: Women in the third trimester of pregnancy and their infants were widely exposed to low-dose PYRs. Infant daily exposure to PYRs may negatively impact toddlers' language development, with the 6-8 months age bracket being a sensitive window. The probability of toddlers' language development delay may be predicted by PYRs metabolites of infants aged 6-8 months.
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http://dx.doi.org/10.1016/j.neuro.2022.08.002DOI Listing
August 2022

A MDM2 inhibitor MX69 inhibits adipocytes adipogenesis and differentiation.

Biochem Biophys Res Commun 2022 Aug 2;625:9-15. Epub 2022 Aug 2.

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & School of Basic Medicine Peking Union Medical College, Beijing, 100005, China. Electronic address:

Adipose tissue, a key regulator of systemic energy homeostasis, can synthesize and store triglycerides to meet long-term energy demands. In response to nutrient overload, adipose tissue expands by hypertrophy or hyperplasia. As an oncogene, MDM2 has exerted diverse biological activities including human development, tissue regeneration, and inflammation, in addition to major oncogenic activities. Recently, some studies indicated that MDM2 plays an important role in adipose tissue function. However, the role of MX69, a MDM2 inhibitor, in adipose tissue function has not been fully elucidated. Here, we administered MX69 intraperitoneally to high-fat diet-induced obesity (DIO) wild type C57BL/6 mice and found that MX69 could promote the body weight and white adipose tissue weight of DIO mice. Moreover, MX69 had no effects on glucose tolerance and insulin sensitivity in DIO mice. And MX69 treatment decreased the size of adipocytes and fat deposition in adipose tissue and inhibited 3T3-L1 preadipocytes differentiation. Mechanistically, MX69 inhibited the protein levels of MDM2 and the mRNA levels of genes related to adipogenesis and differentiation. In summary, our results indicated that MDM2 has a crucial and complex role in regulating adipose tissue function.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.115DOI Listing
August 2022

Isolated nocturnal hypertension in relation to host and environmental factors and clock genes.

J Clin Hypertens (Greenwich) 2022 Aug 9. Epub 2022 Aug 9.

Department of Cardiovascular Medicine, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, State Key Laboratory of Medical Genomics, National Research Centre for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Isolated nocturnal hypertension (INH) is a special type of out-of-office hypertension. Its determinants and pathophysiology remain unclear. In a nested case-control study, we intend to investigate the host, environmental, and genetic factors in relation to INH. Among 2030 outpatients screened from December 2008 till June 2015, 128 patients with INH were identified, and then 128 normotensives were matched according to sex and age. INH was an elevated nocturnal blood pressure (BP ≥120/70 mmHg) in the presence of a normal daytime BP (< 135/85 mmHg). Host factors included age, sex, body mass index, smoking and drinking, sleep time and duration, heart rate, serum lipids, and serum creatinine. Environmental cues encompassed season, ambient temperature, atmospheric pressure, humidity, and wind speed, and genetic cues 29 single-nucleotide polymorphisms (SNPs) in 12 clock genes. Daytime and nighttime BPs averaged 124.9/80.7  and 114.5/73.7 mmHg, respectively, in the INH patients and 121.0/76.5 and 101.8/63.3 mmHg in the normotensive controls. Stepwise logistic regression analyses revealed that INH was associated with nighttime heart rate (P = .0018), sleep duration (P = .0499), and relative humidity (P = .0747). The odds ratios (95% CI) for each 10 beats/min faster nighttime heart rate and 10% lower relative humidity were 1.82 (1.25-2.65) and 0.82 (0.67-1.00), respectively. Irrespective of the genetic models, no significant association was observed between INH and the SNPs (P ≥ .054). In conclusion, INH was associated with host and environmental factors rather than genetic markers.
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http://dx.doi.org/10.1111/jch.14532DOI Listing
August 2022

ARF2-PIF5 interaction controls transcriptional reprogramming in the ABS3-mediated plant senescence pathway.

EMBO J 2022 Aug 9:e110988. Epub 2022 Aug 9.

State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University, Yangling, China.

One of the hallmarks of plant senescence is the global transcriptional reprogramming coordinated by a plethora of transcription factors (TFs). However, mechanisms underlying the interactions between different TFs in modulating senescence remain obscure. Previously, we discovered that plant ABS3 subfamily MATE transporter genes regulate senescence and senescence-associated transcriptional changes. In a genetic screen for mutants suppressing the accelerated senescence phenotype of the gain-of-function mutant abs3-1D, AUXIN RESPONSE FACTOR 2 (ARF2) and PHYTOCHROME-INTERACTING FACTOR 5 (PIF5) were identified as key TFs responsible for transcriptional regulation in the ABS3-mediated senescence pathway. ARF2 and PIF5 (as well as PIF4) interact directly and function interdependently to promote senescence, and they share common target genes such as key senescence promoting genes ORESARA 1 (ORE1) and STAY-GREEN 1 (SGR1) in the ABS3-mediated senescence pathway. In addition, we discovered reciprocal regulation between ABS3-subfamily MATEs and the ARF2 and PIF5/4 TFs. Taken together, our findings reveal a regulatory paradigm in which the ARF2-PIF5/4 functional module facilitates the transcriptional reprogramming in the ABS3-mediated senescence pathway.
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http://dx.doi.org/10.15252/embj.2022110988DOI Listing
August 2022

Enhanced thrombolysis by endovascular low-frequency ultrasound with bifunctional microbubbles in venous thrombosis: and study.

Front Bioeng Biotechnol 2022 22;10:965769. Epub 2022 Jul 22.

State Key Laboratory of Tribology, Tsinghua University, Beijing, China.

There is a need to improve the efficacy and safety of endovascular techniques in venous thrombotic diseases, and microbubble enhanced sonothrombolysis is a promising approach. However, whether endovascular low-frequency ultrasound (LFUS) can be utilized in microbubble enhanced sonothrombolysis is unclear. Here, we present a catheter-based thrombolytic system that combines unfocused low-frequency low-intensity ultrasound with novel fibrin-targeted drug-loaded bifunctional microbubbles. We develop an flow model and an rabbit inferior vena cava (IVC) thrombosis model to evaluate the safety and efficacy of the thrombolytic system. The results indicate that microbubble enhanced sonothrombolysis with endovascular LFUS treatment for 30 min is equally effective compared to pure pharmacologic treatment. Furthermore, the thrombolytic efficacy of this system is safely and substantially improved by the introduction of a fibrin-targeted drug-loaded bifunctional microbubble with a reduction of the fibrinolytic agent dosage by 60%. The microbubble enhanced endovascular LFUS sonothrombolysis system with excellent thrombolytic efficacy may serve as a new therapeutic approach for venous thrombotic diseases.
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http://dx.doi.org/10.3389/fbioe.2022.965769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356075PMC
July 2022

scVAEBGM: Clustering Analysis of Single-Cell ATAC-seq Data Using a Deep Generative Model.

Interdiscip Sci 2022 Aug 8. Epub 2022 Aug 8.

Department of Electrical Engineering and Information Technology, Shandong University of Science and Technology, Jinan, 250031, Shandong, China.

A surge in research has occurred because of current developments in single-cell technologies. Above all, single-cell Assay for Transposase-Accessible Chromatin with high throughput sequencing (scATAC-seq) is a popular approach of analyzing chromatin accessibility differences at the level of single cell, either within or between groups. As a result, it is critical to examine cell heterogeneity at a previously unseen level and to identify both recognized and unknown cell types. However, with the ever-increasing number of cells engendered by technological development and the characteristics of the data, such as high noise, sparsity and dimension, challenges in distinguishing cell types have emerged. We propose scVAEBGM, which integrates a Variational Autoencoder (VAE) with a Bayesian Gaussian-mixture model (BGM) to process and analyze scATAC-seq data. This method combines and takes benefits of a Bayesian Gaussian mixture model to estimate the number of cell types without determining the cluster number in a beforehand. In other words, the size of the clusters is inferred from the data, thus avoiding biases introduced by subjective assessments when manually determining the size of the clusters. Additionally, the method is more robust to noise and can better represent single-cell data in lower dimensions. We also create a further clustering strategy. It is indicated by experiments that further clustering based on the already completed clustering can improve the clustering accuracy again. We test on six public datasets, and scVAEBGM outperforms various dimension reduction baselines. In downstream applications, scVAEBGM can reveal biological cell types.
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http://dx.doi.org/10.1007/s12539-022-00536-wDOI Listing
August 2022

Tractable Method for Rapid Quality Assessment of Therapeutic Antibodies in Harvested Cell Culture Fluid based on FcγRIIIa-Immobilized Magnetic Microspheres.

Anal Chem 2022 Aug 8. Epub 2022 Aug 8.

Pharmaceutical Analysis Department, School of Pharmacy, Fudan University, Shanghai 201203, China.

FcγRIIIa-binding affinity is one of the key factors to ensure the efficacy of many antitumor therapeutic antibodies, which should be monitored along with the titer, protein aggregation, and other critical quality attributes. The conventional workflow for the quality assessment of therapeutic antibodies in harvested cell culture fluid (HCCF) is time-consuming and costly nevertheless. In this study, a tractable method was established for rapid quality assessment of a HCCF sample through differentially extracting IgG with different FcγRIIIa affinity levels using FcγRIIIa-immobilized magnetic microspheres, followed by size exclusion chromatography (SEC) to determine the amount and monomer percentage of IgGs in the preceding eluate. FcγRIIIa-immobilized magnetic microspheres with polydopamine (PDA) and hydrophilic dendrimer (PAMAM) coating (denoted as [email protected]@PAMAM-FcγRIIIa) were synthesized for the first time as magnetic adsorbents. The PDA cladding endowed the composites with good chemical stability in acidic elution buffer, and the PAMAM dendrimer empowered the composites of high ligand immobilization capacity and hydrophilic surface. The labile FcγRIIIa was immobilized under mild conditions. By directly applying a simple magnetic solid phase extraction procedure to treat HCCF, favored IgG species with high FcγRIIIa affinity would be selectively captured by [email protected]@PAMAM-FcγRIIIa composites for subsequent SEC analysis. The monomer peak area value in SEC, which was set as the read-out of the proposed method, correlated directly with the theoretical overall quality of standard-spiked HCCF samples.
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http://dx.doi.org/10.1021/acs.analchem.2c01350DOI Listing
August 2022

The Upregulation of HAS2-AS1 Relates to the Granulosa Cell Dysfunction by Repressing TGF-β Signaling and Upregulating HAS2.

Mol Cell Biol 2022 Aug 8:e0010722. Epub 2022 Aug 8.

Department of Reproductive Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

HAS2 antisense RNA 1 (HAS2-AS1) is a long noncoding RNA that has increased expression in mature granulosa cells (GCs) and contributes to cumulus expansion by regulating HAS2 expression. However, the roles of HAS2-AS1 during the pathological process of polycystic ovary syndrome (PCOS) are still unclear. This study investigated the roles of HAS2-AS1 in patients with PCOS. Here, a significant upregulation of HAS2-AS1 was found in the primary GCs from patients with PCOS, which was positively correlated with the level of the protein HAS2. The knockdown of HAS2 restored the upregulation of HAS2-AS1 in promoting migration but could not restore the effects of HAS2-AS1 overexpression in promoting proliferation and repressing apoptosis. Transforming growth factor β (TGF-β) upregulated HAS2-AS1 levels, while HAS2-AS1 functioned as a feedback inhibition factor repressing TGF-β signaling by inhibiting TGF-β receptor type 2 (TGFBR2) expression. HAS2-AS1 bonded with EZH2 and guided the polycomb complex 2 to the TGFBR2 promoter region. HAS2-AS1 overexpression induced H3K27 hypermethylation in the TGFBR2 promoter region and then repressed TGFBR2 transcription in KGN cells and primary GCs. In conclusion, we identified for the first time that HAS2-AS1 is upregulated in patients with PCOS and represses TGF-β signaling via inducing TGFBR2 promoter region hypermethylation, which allowed us to explore the pathological processes of PCOS.
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http://dx.doi.org/10.1128/mcb.00107-22DOI Listing
August 2022

Transcranial ultrasound stimulation applied in ischemic stroke rehabilitation: A review.

Front Neurosci 2022 22;16:964060. Epub 2022 Jul 22.

Institute of Medical Research, Northwestern Polytechnical University, Xi'an, China.

Ischemic stroke is a serious medical condition that is caused by cerebral vascular occlusion and leads to neurological dysfunction. After stroke, patients suffer from long-term sensory, motor and cognitive impairment. Non-invasive neuromodulation technology has been widely studied in the field of stroke rehabilitation. Transcranial ultrasound stimulation (TUS), as a safe and non-invasive technique with deep penetration ability and a tiny focus, is an emerging technology. It can produce mechanical and thermal effects by delivering sound waves to brain tissue that can induce the production of neurotrophic factors (NFs) in the brain, and reduce cell apoptosis and the inflammatory response. TUS, which involves application of an acoustic wave, can also dissolve blood clots and be used to deliver therapeutic drugs to the ischemic region. TUS has great potential in the treatment of ischemic stroke. Future advancements in imaging and parameter optimization will improve the safety and efficacy of this technology in the treatment of ischemic stroke.
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http://dx.doi.org/10.3389/fnins.2022.964060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355469PMC
July 2022

Portable Heating System Based on a Liquid Metal Bath for Rapid PCR.

ACS Omega 2022 Aug 20;7(30):26165-26173. Epub 2022 Jul 20.

Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 516001, China.

With the outbreak of COVID-19 around the world, rapid and accurate detection of new coronaviruses is the key to stop the transmission of the disease and prevent and control the novel coronavirus, among which polymerase chain reaction (PCR) is the mainstream nucleic acid detection method. A temperature cycling device is the core of the PCR amplification micro-device. The precision of the temperature control and temperature change rate directly affect the efficiency of PCR amplification. This study proposes a new PCR method based on rapid PCR chip optimization of a liquid metal bath, which realizes precise and rapid temperature rise and fall control. We systematically explored the feasibility of using liquid metals with different melting points in the system and proposed a 47 °C bismuth-based liquid metal bath as the heat conduction medium of the system to optimize the system. The heat conduction properties of the thermally conductive silicone oil bath were compared. Compared with the thermally conductive silicone oil bath, thermal cycle efficiency is improved nearly 3 times. The average heating rate of the liquid metal bath is fast, and the temperature control stability is good, which can significantly reduce the hysteresis, and the temperature change curve is more gentle, which can greatly improve the efficiency of PCR amplification. The results of gene amplification using rat DNA as the template and SEC61A as the target also indicate that the system can be successfully used in PCR devices, and the types of PCR containers can be not limited to PCR tubes. Based on the experiment, we proved that the PCR method optimized by the liquid metal bath multi-gene rapid PCR chip can further improve the temperature response speed. It has the advantages of accurate data, fast response speed, low price, safety, and environmental protection and can effectively reduce the time of PCR and improve the application efficiency. As far as we know, this is the first international report on using a liquid metal bath to do rapid-cooling PCR.
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http://dx.doi.org/10.1021/acsomega.2c01824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352155PMC
August 2022

The long-term outcomes of preterm infants receiving non-invasive high-frequency oscillatory ventilation.

Front Pediatr 2022 22;10:865057. Epub 2022 Jul 22.

Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

Objective: To investigate the clinical outcomes of preterm infants who received non-invasive high-frequency oscillatory ventilation following extubation in a neonatal intensive care unit.

Methods: Infants born between 25 and 34 weeks of gestation with a birth weight of <1,500 g, who were admitted into the neonatal intensive care unit of Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, China, requiring mechanical ventilation on admission were randomized to the non-invasive high-frequency ventilation group, nasal intermittent positive pressure ventilation group, or nasal continuous positive airway pressure group following extubation. Their respiratory and neurodevelopmental outcomes were assessed at 12 and 24 months of corrected age.

Results: Among 149 preterm infants who underwent randomization, 139 completed their treatment in the neonatal intensive care unit (45, 47, 47 in the non-invasive high-frequency ventilation group, nasal intermittent positive pressure ventilation group, or nasal continuous positive airway pressure group, respectively), 113 were assessed at 12-month corrected age, and 110 of 113 were assessed again at 24-month corrected age. There were no differences in the number of times bronchitis, pneumonia, wheezing episodes, and re-hospitalization rates appeared due to respiratory diseases among the three groups ( > 0.05); the pulmonary function tests at 12-month corrected age showed respiratory rate, tidal volume, inspiratory time/expiratory time, time to peak expiratory flow/expiratory time, volume at peak expiratory flow/expiratory volume, expiratory flow at 25, 50, and 75% tidal volume were all similar among infants from the 3 groups ( > 0.05). There were no differences in the rates of neurodevelopmental impairment among the three groups at 24-month corrected age ( > 0.05).

Conclusion: As post-extubation respiratory support in preterm infants, non-invasive high-frequency ventilation did not increase the rates of long-term respiratory morbidities and neurodevelopmental impairment compared with nasal intermittent positive pressure ventilation and nasal continuous positive airway pressure.
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http://dx.doi.org/10.3389/fped.2022.865057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353142PMC
July 2022

Using Alzheimer's disease blood tests to accelerate clinical trial enrollment.

Alzheimers Dement 2022 Aug 7. Epub 2022 Aug 7.

Olin Business School, Washington University, St. Louis, Missouri, USA.

Introduction: Screening potential participants in Alzheimer's disease (AD) clinical trials with amyloid positron emission tomography (PET) is often time consuming and expensive.

Methods: A web-based application was developed to model the time and financial cost of screening for AD clinical trials. Four screening approaches were compared; three approaches included an AD blood test at different stages of the screening process.

Results: The traditional screening approach using only amyloid PET was the most time consuming and expensive. Incorporating an AD blood test at any point in the screening process decreased both the time and financial cost of trial enrollment. Improvements in AD blood test accuracy over currently available tests only marginally increased savings. Use of a high specificity cut-off may improve the feasibility of screening with only an AD blood test.

Discussion: Incorporating AD blood tests into screening for AD clinical trials may reduce the time and financial cost of enrollment.

Highlights: The time and cost of enrolling participants in Alzheimer's disease (AD) clinical trials were modeled. A web-based application was developed to enable evaluation of key parameters. AD blood tests may decrease the time and financial cost of clinical trial enrollment. Improvements in AD blood test accuracy only marginally increased savings. Use of a high specificity cut-off may enable screening with only an AD blood test.
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http://dx.doi.org/10.1002/alz.12754DOI Listing
August 2022

Correlates of cancer prevalence across census tracts in the United States: A Bayesian machine learning approach.

Spat Spatiotemporal Epidemiol 2022 Aug 27;42:100522. Epub 2022 May 27.

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Preventive measures, health behaviors, environmental exposures, and sociodemographic characteristics affect individual-level cancer risks. It is unclear how they influence neighborhood-level cancer risks. We developed a large-scale neighborhood health dataset for 72,337 census tracts in the United States by combining data from three publicly available sources. We used Bayesian additive regression trees to identify the most important predictors of tract-level cancer prevalence among adults (age ≥18 years), and examined their impact on cancer prevalence using partial dependence plots. The five most important census tract-level correlates of cancer prevalence were the proportion of population who were aged 65 years and older, had routine checkup and were non-Hispanic White, the proportion of houses built before 1960, and the proportion of population living below the poverty line. The identified predictors of neighborhood-level cancer prevalence may inform public health practitioners and policymakers to prioritize the improvement of environmental and neighborhood factors in reducing the cancer burden.
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http://dx.doi.org/10.1016/j.sste.2022.100522DOI Listing
August 2022

Effectiveness and safety of tafluprost in primary open-angle glaucoma and ocular hypertension: a post-marketing phase IV study in China.

BMC Ophthalmol 2022 Aug 5;22(1):332. Epub 2022 Aug 5.

Department of Cataract and Glaucoma, Wuhan Eyegood Ophthalmic Hospital, Wuhan, 430064, Hubei Province, China.

Background: Prostaglandin analogs (PGAs) are the first-line treatment for primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study aimed to confirm the effectiveness and safety of Tapros® (0.0015% tafluprost eye drops) in Chinese patients with POAG and OH.

Methods: This phase IV, multicenter, non-comparative, prospective study enrolled patients with POAG and OH in China between 12/27/2017 and 04/15/2020. Patients who were treatment-naïve or untreated within one month (group A) or with unreached intraocular pressure (IOP) target after previous monotherapy of other PGAs (group B) or non-PGA IOP-lowering drugs (group C) were treated with 0.0015% tafluprost for three months. The IOP reduction, response rate, and safety were observed.

Results: There were 165, 89, and 31 patients in groups A, B, and C, with baseline IOPs of 22.4 ± 4.7, 21.0 ± 3.5, and 22.5 ± 3.2 mmHg, respectively. The least-square means and percentages of IOP reduction at 3 months for groups A, B, and C were 4.7 (19.8%), 1.6 (6.1%), and 4.6 mmHg (20.3%), respectively. A significant reduction in IOP was observed at each visit compared with baseline (all P < 0.05). At the final visit, 57.0% of the participants in group A achieved an IOP reduction of ≥ 20%, while 40.4% and 77.4% in groups B and C achieved an IOP reduction of ≥ 10%. Fifty-eight treatment-related adverse events occurred in 46 participants (15.7%), of which the most common one was conjunctival hyperemia (34/293, 11.6%).

Conclusions: Tafluprost showed a sustained and significant effect with tolerable adverse events in Chinese patients with POAG and OH who were treatment-naïve or untreated within one month or received prior treatments with unsatisfying outcomes.
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http://dx.doi.org/10.1186/s12886-022-02553-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356508PMC
August 2022

Transcription factors Vrf1 and Hox7 coordinately regulate appressorium maturation in the rice blast fungus Magnaporthe oryzae.

Microbiol Res 2022 Jul 30;263:127141. Epub 2022 Jul 30.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, College of Life Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, China. Electronic address:

Magnaporthe oryzae infects rice, wheat and other grass crops through appressoria. The formation of the appressorium is regulated by the external environment, signal transduction pathways, and transcription factors. Transcription factors Vrf1 and Hox7 are involved in the regulation of appressorium formation. In this study, we demonstrate that Vrf1 and Hox7 play vital roles in coordinately regulating appressorium maturation. In strain 70-15, deletion of VRF1 resulted in the inability to continue melanization and maturation of the incipient appressorium, and deletion of HOX7 also resulted in defects in appressorium melanization and maturation. The defects in appressorium formation in Δhox7Δvrf1 were similar to those in Δhox7 and Δvrf1. The gene expression profiles of the incipient appressoria at 5 h post-inoculation (hpi) showed that the expression levels of 704 genes (25.94 % of all differentially expressed genes in the three mutants) were significantly downregulated (606 genes) or upregulated (98 genes). In the appressoria of Δhox7, Δvrf1, and Δhox7Δvrf1 at 5 hpi, the expression level of genes related to cell wall remodeling was changed. Genes for melanin synthesis, chitin and glucan degradation, and extracellular cell wall degrading enzyme were significantly downregulated, while genes for chitin and glucan synthesis were upregulated. After 8 hpi, the incipient appressoria of Δhox7, Δvrf1, and Δhox7Δvrf1 regerminated and formed swollen hyphal-like structures with multiple nuclei. The ratio of the nuclear number of the hyphal-like structures of Δhox7, Δhox7Δvrf1, and Δvrf1 was close to 6:4:2 at 24 hpi. Therefore, although Vrf1 and Hox7 are somewhat functionally different, they synergistically regulate appressorium maturation in M. oryzae.
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http://dx.doi.org/10.1016/j.micres.2022.127141DOI Listing
July 2022

Global phosphoproteomic analysis identified key kinases regulating male meiosis in mouse.

Cell Mol Life Sci 2022 Aug 5;79(8):467. Epub 2022 Aug 5.

State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China.

Meiosis, a highly conserved process in organisms from fungi to mammals, is subjected to protein phosphorylation regulation. Due to the low abundance of phosphorylation, there is a lack of systemic characterization of phosphorylation regulation of meiosis in mammals. Using the phosphoproteomic approach, we profiled large-scale phosphoproteome of purified primary spermatocytes undergoing meiosis I, and identified 14,660 phosphorylation sites in 4419 phosphoproteins. Kinase-substrate phosphorylation network analysis followed by in vitro meiosis study showed that CDK9 was essential for meiosis progression to metaphase I and had enriched substrate phosphorylation sites in proteins involved in meiotic cell cycle. In addition, histones and epigenetic factors were found to be widely phosphorylated. Among those, HASPIN was found to be essential for male fertility. Haspin knockout led to misalignment of chromosomes, apoptosis of metaphase spermatocytes and a decreased number of sperm by deregulation of H3T3ph, chromosomal passenger complex (CPC) and spindle assembly checkpoint (SAC). The complicated protein phosphorylation and its important regulatory functions in meiosis indicated that in-depth studies of phosphorylation-mediated signaling could help us elucidate the mechanisms of meiosis.
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http://dx.doi.org/10.1007/s00018-022-04507-8DOI Listing
August 2022

In-situ formable dextran/chitosan-based hydrogels functionalized with collagen and EGF for diabetic wounds healing.

Biomater Adv 2022 May 25;136:212773. Epub 2022 Mar 25.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, PR China. Electronic address:

Delayed or non-healing skin wounds causing gangrene or even amputation, greatly threats diabetic patients lives. Herein, a bioactive, in-situ formable hydrogel based wound dressing was designed through simple Schiff base reaction. Oxidized dextran (OD) and carboxyethyl chitosan (CEC) were crosslinked together and applied as the main porous framework of hydrogel. To improve the mechanical strength and biocompatibility, collagen (Col) and EGF (Epidermal Growth Factor) were introduced into OD-CEC precursors: (1) after addition of only Col, the mechanical strength of hydrogels was improved by participating the functional -NH group of Col into the crosslinking process. Moreover, swelling ratio was as high as 750% on 3%OD-3%CEC-Col (water retention rate was 65 wt% after 7 days). (2) Once we introduced both Col and EGF into the OD-CEC hydrogel, the proliferation of mouse embryonic fibroblast (NIH 3T3) cells was promoted using 3%OD-3%CEC-Col/EGF, an accelerated wound healing was observed with 86% wound closure after only 14 operative days. Hematoxylin and eosin (H&E) staining and Masson staining indicated the synergy of Col and EGF might promote new tissue's formation, well collagen distributions and thus accelerate skin regeneration, presenting great potentials in wound healing of diabetic patients.
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http://dx.doi.org/10.1016/j.bioadv.2022.212773DOI Listing
May 2022

Effect of Pathogenesis-Based Individualized Thrombectomy on Treatment Result and Prognosis of Acute Intracranial LargeArtery Occlusion Patients.

Turk Neurosurg 2022 Feb 28. Epub 2022 Feb 28.

Cangzhou Central Hospital, Department of Neurovascular Intervention, Cangzhou City 061000, Hebei Province, China.

Aim: This study aims to explore the effect of pathogenesis-based individualised thrombectomy on the clinical results and prognoses of acute intracranial large-artery occlusion.

Material And Methods: A total of 151 patients were included in this prospective study and divided into the control group (stent thrombectomy, 53 cases), a direct aspiration first pass technique (ADAPT) group (52 cases) and the stent group (stent thrombectomy or a combination of stent thrombectomy and ADAPT, 46 cases) based on whether stent or ADAPT was used. We compared and analysed the patients' general information, the National Institutes of Health Stroke Scale (NHISS) score at admission, the time between the end of arteriography and revascularisation, the number of thrombectomies, the modified Rankin scale (mRS) score at three months and complications in the three groups.

Results: Compared with the control group, the time between the end of arteriography and revascularisation in the ADAPT group was significantly reduced (P 0.05), and the patency rate after one thrombectomy significantly increased (P 0.05). The positive prognosis rate was significantly increased in the stent and ADAPT groups compared with the control group (P 0.05).

Conclusion: The application of the ADAPT technique in patients with embolism-induced cerebral infarction can reduce the time of revascularisation. The use of stents in patients with atherosclerosis-induced cerebral infarction can increase the patency rate after one thrombectomy.
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http://dx.doi.org/10.5137/1019-5149.JTN.37008-21.2DOI Listing
February 2022

Biodegradation of Gramineous Lignocellulose by (Orthoptera: Acridoidea).

Front Bioeng Biotechnol 2022 19;10:943692. Epub 2022 Jul 19.

College of Life Science, Henan Agricultural University, Zhengzhou, China.

Exploring an efficient and green pretreatment method is an important prerequisite for the development of biorefinery. It is well known that locusts can degrade gramineous lignocellulose efficiently. Locusts can be used as a potential resource for studying plant cell wall degradation, but there are few relative studies about locusts so far. Herein, some new discoveries were revealed about elucidating the process of biodegradation of gramineous lignocellulose in . The enzyme activity related to lignocellulose degradation and the content of cellulose, hemicellulose, and lignin in the different gut segments of locusts fed corn leaves were measured in this study. A series of characterization analyses were conducted on corn leaves and locust feces, which included field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction pattern (XRD), and thermogravimetric (TG) analysis. These results showed that the highest activities of carboxymethyl cellulase (CMCase), filter paper cellulase (FPA), and xylanase were obtained in the foregut of locusts, which strongly indicated that the foregut was the main lignocellulose degradation segment in locusts; furthermore, the majority of nutritional components were absorbed in the midgut of locusts. The activity of CMCase was significantly higher than that of xylanase, and manganese peroxidase (MnPase) activity was lowest, which might be due to the basic nutrition of locusts being cellulose and hemicellulose and not lignin based on the results of FE-SEM, FTIR, XRD, and TG analysis. Overall, these results provided a valuable insight into lignocellulosic degradation mechanisms for understanding gramineous plant cell wall deconstruction and recalcitrance in locusts, which could be useful in the development of new enzymatic pretreatment processes mimicking the locust digestive system for the biochemical conversion of lignocellulosic biomass to fuels and chemicals.
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http://dx.doi.org/10.3389/fbioe.2022.943692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343829PMC
July 2022

The Relative Body Weight Gain From Early to Middle Life Adulthood Associated With Later Life Risk of Diabetes: A Nationwide Cohort Study.

Front Endocrinol (Lausanne) 2022 19;13:927067. Epub 2022 Jul 19.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Aim: To determine the effect of decade-based body weight gain from 20 to 50 years of age on later life diabetes risk.

Methods: 35,611 non-diabetic participants aged ≥ 50 years from a well-defined nationwide cohort were followed up for average of 3.6 years, with cardiovascular diseases and cancers at baseline were excluded. Body weight at 20, 30, 40, and 50 years was reported. The overall 30 years and each 10-year weight gain were calculated from the early and middle life. Cox regression models were used to estimate risks of incident diabetes.

Results: After 127,745.26 person-years of follow-up, 2,789 incident diabetes were identified (incidence rate, 2.18%) in 25,289 women (mean weight gain 20-50 years, 7.60 kg) and 10,322 men (7.93 kg). Each 10-kg weight gain over the 30 years was significantly associated with a 39.7% increased risk of incident diabetes (95% confidence interval [CI], 1.33-1.47); weight gain from 20-30 years showed a more prominent effect on the risk of developing diabetes before 60 years than that of after 60 years (Hazard ratio, HR = 1.084, 95% CI [1.049-1.121], 0.0001 vs. 1.015 [0.975-1.056], = 0.4643; =0.0293). It showed a stable effect of the three 10-year intervals weight gain on risk of diabetes after 60 years (HR=1.055, 1.038, 1.043, respectively, all < 0.0036).

Conclusions: The early life weight gain showed a more prominent effect on developing diabetes before 60 years than after 60 years; however, each-decade weight gain from 20 to 50 years showed a similar effect on risk developing diabetes after 60 years.
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http://dx.doi.org/10.3389/fendo.2022.927067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343618PMC
August 2022

Microbial and Transcriptomic Profiling Reveals Diet-Related Alterations of Metabolism in Metabolic Disordered Mice.

Front Nutr 2022 19;9:923377. Epub 2022 Jul 19.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Metabolic disorders are the prelude of metabolic diseases, which are mainly due to the high-energy intake and genetic contribution. High-fat diet (HFD) or high-sucrose diet is widely used for inducing metabolic disorders characterized by increased body weight, insulin resistance, hepatic steatosis, and alteration of gut microbiome. However, the triangle relationship among diets, gut microbiome, and host metabolism is poorly understood. In our study, we investigated the dynamic changes in gut microbiota, and host metabolism in mice that were fed with either chow diet, HFD, or chow diet with 30% sucrose in drinking water (HSD) for continued 12 weeks. The gut microbiota was analyzed with 16S rDNA sequencing on feces. Hepatic gene expression profile was tested with transcriptomics analysis on liver tissue. The host metabolism was evaluated by measuring body weight, insulin sensitivity, serum lipids, and expression of proteins involved in lipid metabolism of liver. The results showed that HFD feeding affected body weight, insulin resistance, and hepatic steatosis more significantly than HSD feeding. 16S rRNA gene sequencing showed that HFD rapidly and steadily suppressed species richness, altered microbiota structure and function, and increased the abundance of bacteria responsible for fatty acid metabolism and inflammatory signaling. In contrast, HSD had minor impact on the overall bacteria structure or function but activated microbial bile acid biosynthesis. Fecal microbiota transplantation suggested that some metabolic changes induced by HFD or HSD feeding were transferrable, especially in the weight of white adipose tissue and hepatic triglyceride level that were consistent with the phenotypes in donor mice. Moreover, transcriptomic results showed that HFD feeding significantly inhibited fatty acid degradation and increase inflammation, while HSD increased hepatic lipogenesis and inhibited primary bile acid synthesis alternative pathway. In general, our study revealed the dynamic and diversified impacts of HFD and HSD on gut microbiota and host metabolism.
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http://dx.doi.org/10.3389/fnut.2022.923377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344047PMC
July 2022

Nivolumab Versus Sorafenib as First-Line Therapy for Advanced Hepatocellular Carcinoma: A Cost-Effectiveness Analysis.

Front Pharmacol 2022 19;13:906956. Epub 2022 Jul 19.

Department of Pharmacy, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

Nivolumab improves overall survival (OS) and is associated with fewer adverse events than sorafenib for the treatment of advanced hepatocellular carcinoma (aHCC). However, the cost-effectiveness of nivolumab compared with sorafenib treatment for aHCC remains unclear. This study evaluated the cost-effectiveness of nivolumab and sorafenib in the treatment of aHCC. A partitioned survival model that included three mutually exclusive health states was used to evaluate the cost-effectiveness of nivolumab and sorafenib for treating aHCC. The clinical characteristics and outcomes of the patients in the model were obtained from the CheckMate 459. We performed deterministic one-way sensitivity and probabilistic sensitivity analyses to evaluate the robustness of the model. Subgroup analyses were also performed. Costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were measured. The base case analysis showed that compared with sorafenib, treatment with nivolumab was associated with an increment of 0.50 (2.45 vs. 1.95) life-years and an increment of 0.32 (1.59 vs. 1.27) QALYs, as well as a $69,762 increase in cost per patient. The ICER was $220,864/QALY. The INHB and INMB were -0.15 QALYs and -$22,362 at a willingness-to-pay (WTP) threshold of $150,000/QALY, respectively. The probabilistic sensitivity analysis demonstrated that the probability of nivolumab being cost-effective was only 10.38% at a WTP threshold of $150,000/QALY. The model was most sensitive to the costs of sorafenib and nivolumab according to the one-way sensitivity analysis. When the price of sorafenib exceeded $0.93/mg or nivolumab was less than $24.23/mg, nivolumab was more cost-effective. The subgroup analysis illustrated that the probability of cost-effectiveness was >50% in the Barcelona Clinic Liver Cancer Stage B subgroups for nivolumab at a WTP threshold of $150,000/QALY. This study also showed that the probability of cost-effectiveness was <50% in most subgroups. Nivolumab was not cost-effective, although it was associated with better clinical benefit and a favorable safety profile for the treatment of aHCC compared with sorafenib from the third-party payer perspective in the United States. If the price of nivolumab is substantially reduced, favorable cost-effectiveness can be achieved among patients with aHCC.
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http://dx.doi.org/10.3389/fphar.2022.906956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343987PMC
July 2022
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