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1.
Circ Res ; 134(4): 445-458, 2024 02 16.
Article in English | MEDLINE | ID: mdl-38359092

ABSTRACT

Cardiovascular disease has been the leading cause of mortality and morbidity worldwide in the past 3 decades. Multiple cell lineages undergo dynamic alternations in gene expression, cell state determination, and cell fate conversion to contribute, adapt, and even modulate the pathophysiological processes during disease progression. There is an urgent need to understand the intricate cellular and molecular underpinnings of cardiovascular cell development in homeostasis and pathogenesis. Recent strides in lineage tracing methodologies have revolutionized our understanding of cardiovascular biology with the identification of new cellular origins, fates, plasticity, and heterogeneity within the cardiomyocyte, endothelial, and mesenchymal cell populations. In this review, we introduce the new technologies for lineage tracing of cardiovascular cells and summarize their applications in studying cardiovascular development, diseases, repair, and regeneration.


Subject(s)
Cardiovascular Diseases , Cardiovascular System , Humans , Cell Differentiation , Cell Lineage , Cardiovascular Diseases/genetics , Myocytes, Cardiac
2.
Proc Natl Acad Sci U S A ; 119(13): e2120336119, 2022 03 29.
Article in English | MEDLINE | ID: mdl-35320046

ABSTRACT

SignificanceTissue fibrotic diseases, for example of the liver and lung, represent a huge unmet medical need. In this study, using single-cell RNA sequencing, cytometry by time of flight (CyTOF), tissue imaging, and functional assays, we identify a complex vascular niche in Dupuytren's disease (DD), a common localized fibrotic condition of the palm, where early-disease-stage tissue can be accessed readily. We uncover a population of myofibroblast precursors within the pericyte compartment and demonstrate that the endothelium instructs the differentiation of functionally distinct stromal cells, thereby orchestrating discrete microenvironments in the fibrotic milieu. Together, these findings provide a basis for the concept of targeting blood vessel signaling to control the progression of human fibrosis.


Subject(s)
Dupuytren Contracture , Myofibroblasts , Dupuytren Contracture/genetics , Dupuytren Contracture/pathology , Fibrosis , Humans , Myofibroblasts/pathology , Phenotype , Stromal Cells , Tumor Microenvironment
3.
J Cell Mol Med ; 28(1): e18020, 2024 01.
Article in English | MEDLINE | ID: mdl-37909722

ABSTRACT

Anti-angiogenesis is a promising therapeutic strategy for delaying tumour progression that offers, new hope for gastric cancer targeted therapy. The purpose of this study was to investigate the precise mechanism by which Kin of IRRE-like protein 1 (KIRREL) contributes to the development of gastric cancer, particularly in terms of tumour angiogenesis. Differential expression of KIRREL in tissues and cells was detected using quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. A bioinformatics analysis was conducted to screen for the function and pathway enrichment of KIRREL in gastric cancer. Lentivirus-induced KIRREL silencing in SNU-5 cells and lentivirus-induced KIRREL overexpression in AGS cells were used to study the effect of KIRREL on the proliferation, cell cycle and angiogenesis of gastric cancer cells. Moreover, the expressions of PI3K, P-PI3K, AKT, P-AKT, mTOR, P-mTOR, HIF-1α and VEGF were also detected. Gastric cancer tissues and cells had high levels of KIRREL expression, which is associated with the proliferation, cell cycle and angiogenesis of gastric cancer cells. After silencing and overexpressing KIRREL in SNU-5 and AGS cells, respectively, the proliferation and angiogenesis of SNU-5 cells were inhibited, while the proliferation and angiogenesis of AGS cells were promoted. According to a bioinformatics analysis of the KIRREL gene, angiogenesis regulation and the PI3K/AKT pathway were highly connected. The PI3K/AKT/mTOR pathway was repressed and stimulated by KIRREL silencing and overexpression, respectively. IGF-1, an AKT agonist, and LY294002, an inhibitor, reversed the effects of KIRREL silencing and overexpression on the PI3K/AKT/mTOR pathway and on gastric cancer cell proliferation and angiogenesis. KIRREL may mediate the proliferation and angiogenesis of gastric cancer cells through the PI3K/AKT/mTOR signalling pathway. These findings could help in the further development of potential anti-angiogenesis targets.


Subject(s)
Proto-Oncogene Proteins c-akt , Stomach Neoplasms , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Stomach Neoplasms/genetics , Angiogenesis , Cell Line, Tumor , Cell Proliferation/genetics , TOR Serine-Threonine Kinases/metabolism
4.
BMC Genomics ; 25(1): 112, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38273235

ABSTRACT

BACKGROUND: Auxin transcription factor (ARF) is an important transcription factor that transmits auxin signals and is involved in plant growth and development as well as stress response. However, genome-wide identification and responses to abiotic and pathogen stresses of the ARF gene family in Cucurbita pepo L, especially pathogen stresses, have not been reported. RESULTS: Finally, 33 ARF genes (CpARF01 to CpARF33) were identified in C.pepo from the Cucurbitaceae genome database using bioinformatics methods. The putative protein contains 438 to 1071 amino acids, the isoelectric point is 4.99 to 8.54, and the molecular weight is 47759.36 to 117813.27 Da, the instability index ranged from 40.74 to 68.94, and the liposoluble index ranged from 62.56 to 76.18. The 33 genes were mainly localized in the nucleus and cytoplasm, and distributed on 16 chromosomes unevenly. Phylogenetic analysis showed that 33 CpARF proteins were divided into 6 groups. According to the amino acid sequence of CpARF proteins, 10 motifs were identified, and 1,3,6,8,10 motifs were highly conserved in most of the CpARF proteins. At the same time, it was found that genes in the same subfamily have similar gene structures. Cis-elements and protein interaction networks predicted that CpARF may be involved in abiotic factors related to the stress response. QRT-PCR analysis showed that most of the CpARF genes were upregulated under NaCl, PEG, and pathogen treatment compared to the control. Subcellular localization showed that CpARF22 was localized in the nucleus. The transgenic Arabidopsis thaliana lines with the CpARF22 gene enhanced their tolerance to salt and drought stress. CONCLUSION: In this study, we systematically analyzed the CpARF gene family and its expression patterns under drought, salt, and pathogen stress, which improved our understanding of the ARF protein of zucchini, and laid a solid foundation for functional analysis of the CpARF gene.


Subject(s)
Cucurbita , Phylogeny , Cucurbita/genetics , Cucurbita/metabolism , Droughts , Plant Proteins/genetics , Plant Proteins/metabolism , Salt Stress/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Indoleacetic Acids , Stress, Physiological/genetics , Gene Expression Regulation, Plant
5.
Ann Plast Surg ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38896852

ABSTRACT

BACKGROUND: Reconstruction of head and neck soft tissue defects with bone exposure is both challenging and technically demanding for plastic surgeon. Objectives in head and neck soft tissue defects with bone exposure reconstruction are consistent restoration of functionality while also improving appearance. This study retrospectively analyzed the results of head and neck reconstructions using various types of free flaps over the past 4 years. METHODS: A retrospective analysis was conducted from June 2019 to June 2023 on 12 patients treated at our hospital for head and neck soft tissue defects with bone exposure due to various causes. These included 4 cases of trauma from car accidents, 1 burn case, and 7 postoperative malignant tumor removals. The defect sizes ranged from 4 × 6 to 15 × 45 cm. Different free flaps were used for repair based on the defect, including 6 anterolateral thigh flaps, 3 forearm flaps, 2 latissimus dorsi flaps, and 1 dorsalis pedis flap. Flaps were designed and harvested to match the defect size and transplanted via anastomosed vessels. RESULTS: All 12 flaps survived successfully. One patient required flap thinning surgery postoperatively. All patients were followed up for over 3 months, showing good color and texture of the transplanted flaps, satisfactory healing, and significant aesthetic improvement. Donor sites showed significant scarring without functional impairment. CONCLUSION: Free flap repair for head and neck soft tissue defects with bone exposure is feasible and yields good results.

6.
Angew Chem Int Ed Engl ; 63(6): e202318344, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38126567

ABSTRACT

Sulfilimines, the aza-variants of sulfoxides, are key structural motifs in natural products, pharmaceuticals, and agrochemicals; and sulfilimine synthesis is therefore important in organic chemistry. However, methods for radical sulfilimination remain elusive, and as a result, the structural diversity of currently available sulfilimines is limited. Herein, we report the first protocol for decarboxylative radical sulfilimination reactions between sulfenamides and N-hydroxyphthalimide esters of primary, secondary, and tertiary alkyl carboxylic acids, which were achieved via a combination of photoredox, copper, and Brønsted base catalysis. This novel protocol provided a wide variety of sulfilimines, in addition to serving as an efficient route for the synthesis of S-alkyl/S-aryl homocysteine sulfilimines and S-(4-methylphenyl) homocysteine sulfoximine. Moreover, it could be used for late-stage introduction of a sulfilimine group into structurally complex molecules, thereby avoiding the need to preserve labile organosulfur moieties through multistep synthetic sequences. A mechanism involving photocatalytic substrate transformation and copper-mediated C(sp3 )-S bond formation is proposed.

7.
Biochem Biophys Res Commun ; 687: 149215, 2023 12 20.
Article in English | MEDLINE | ID: mdl-37949027

ABSTRACT

The platelet-derived growth factor (PDGF) and its receptor, PDGFRα, are critical for tissue development and injury repair. To track PDGFRα-expressing cells in vivo, we generated a knock-in mouse line that expresses green fluorescent protein (GFP) under the control of the PDGFRα promoter. This genetic tool enabled us to detect PDGFRα expression in various organs during both neonatal and adult stages. Additionally, we confirmed the correlation between endogenous PDGFRα and transgenic PDGFRα expression using mouse injury models, showing the potential of this genetic reporter for studying PDGFRα-mediated signaling pathways and developing therapeutic strategies. Overall, the PDGFRα-GFP knock-in mouse line serves as a valuable tool for investigating the biology of PDGFRα and its role in normal development and disease.


Subject(s)
Fibroblasts , Receptor, Platelet-Derived Growth Factor alpha , Mice , Animals , Receptor, Platelet-Derived Growth Factor alpha/genetics , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Mice, Transgenic , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Disease Models, Animal , Fibroblasts/metabolism
8.
Development ; 147(4)2020 02 17.
Article in English | MEDLINE | ID: mdl-31988189

ABSTRACT

Cellular proliferation is a basic process during organ development, tissue homeostasis and disease progression. Likewise, after injury typically multiple cell lineages respond to various cues and proliferate to initiate repair and/or remodeling of the injured tissue. Unravelling the specific role of proliferation of one cell type and its lineage in the context of the whole organism during tissue regeneration and/or disease progression would provide valuable information on these processes. Here, we report a new genetic system that allows cell proliferation to be inhibited in a tissue-specific manner. We generated Cre- or Dre-inducible p21-GFP (ip21-GFP) transgenic mice that enable experimentally induced permanent cell cycle arrest of specific cell lineages of interest, while genetically marking these cells. This system allows for the inhibition of pathogenic cell proliferation. We found that cardiac fibroblast proliferation inhibition significantly reduced scar formation, and promoted neovascularization and cardiomyocyte survival. Additionally, we found that inhibition of one type of cell proliferation (namely, hepatocytes) induces the lineage conversion of another type cells (i.e. ductal cells) during tissue regeneration. These results validate the use of ip21-GFP mice as a new genetic tool for cell lineage-specific inhibition of cell proliferation in vivo.


Subject(s)
Cell Proliferation , Gene Expression Regulation , Genetic Techniques , Alleles , Animals , Cell Lineage , Cyclin-Dependent Kinase Inhibitor p21/physiology , Female , Fibroblasts/physiology , Green Fluorescent Proteins , Heart/growth & development , Heart/physiology , Hepatocytes/cytology , Hepatocytes/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Myocardial Infarction/pathology , Myocytes, Cardiac/cytology
9.
BMC Plant Biol ; 23(1): 503, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37858063

ABSTRACT

BACKGROUND: Quinoa is an important economic crop, drought is one of the key factors affecting quinoa yield. Clarifying the adaptation strategy of quinoa to drought is conducive to cultivating drought-tolerant varieties. At present, the study of quinoa on drought stress-related metabolism and the identification of related metabolites are still unknown. As a direct feature of biochemical functions, metabolites can reveal the biochemical pathways involved in drought response. RESULT: Here, we studied the physiological and metabolic responses of drought-tolerant genotype L1 and sensitive genotype HZ1. Under drought conditions, L1 had higher osmotic adjustment ability and stronger root activity than HZ1, and the relative water content of L1 was also higher than that of HZ1. In addition, the barrier-to- sea ratio of L1 is significantly higher than that of HZ1. Using untargeted metabolic analysis, a total of 523, 406, 301 and 272 differential metabolites were identified in L1 and HZ1 on day 3 and day 9 of drought stress. The key metabolites (amino acids, nucleotides, peptides, organic acids, lipids and carbohydrates) accumulated differently in quinoa leaves. and HZ1 had the most DEMs in Glycerophospholipid metabolism (ko00564) and ABC transporters (ko02010) pathways. CONCLUSION: These results provide a reference for characterizing the response mechanism of quinoa to drought and improving the drought tolerance of quinoa.


Subject(s)
Chenopodium quinoa , Chenopodium quinoa/genetics , Chenopodium quinoa/metabolism , Droughts , Metabolomics/methods , Genotype , Water/metabolism
10.
Mod Pathol ; 36(4): 100050, 2023 04.
Article in English | MEDLINE | ID: mdl-36788077

ABSTRACT

B-cell maturation antigen (BCMA) is a promising target for the treatment of multiple myeloma (MM) because the expression of this protein is largely limited to B-cell sets, plasma cells, MM, and other B-cell malignancies. Early studies assessing BCMA protein expression and localization have used insufficiently qualified immunohistochemistry assays, which have reported broad ranges of BCMA expression. As a result, our understanding of BCMA tissue expression derived from these data is limited, specifically the prevalence of BCMA expression on the cell surface/membrane, which has mechanistic relevance to the antimyeloma activity of several novel biotherapeutics. Here, we report on the qualification and application of a novel anti-BCMA immunohistochemistry antibody, 805G12. This antibody shows robust detection of BCMA in formalin-fixed, decalcified bone marrow tissue and provides key insights into membrane BCMA expression. The clone 805G12, which was raised against an intracellular C-terminal domain peptide of membrane BCMA, exhibited increased sensitivity and superior specificity across healthy and diseased tissue compared with the frequently referenced commercial reagent AF193. The new clone also demonstrated a broad range of expression of BCMA in MM and diffuse large B-cell lymphoma specimens. Additionally, cross-reactivity with closely related tumor necrosis factor receptor family members was observed with AF193 but not with 805G12. Furthermore, via established 805G12 and other independent BCMA assays, it was concluded that proteolytic processing by γ-secretase contributes to the levels of BCMA localized to the plasma membrane. As BCMA-directed therapeutics emerge to address the need for more effective treatment in the relapsed or refractory MM disease setting, the implementation of a qualified assay would ensure that reliable and consistent data on BCMA surface expression are used to inform clinical trial decisions and patient responses.


Subject(s)
Multiple Myeloma , Humans , Multiple Myeloma/pathology , Immunohistochemistry , Immunotherapy, Adoptive , B-Cell Maturation Antigen/metabolism , Plasma Cells/pathology
11.
Int J Colorectal Dis ; 38(1): 31, 2023 Feb 09.
Article in English | MEDLINE | ID: mdl-36757427

ABSTRACT

AIMS: To evaluate the impact of SARS-CoV-2 vaccine on IBD activity. METHODS: Adult IBD patients from five large IBD centers in China were enrolled and followed up for 6 months. Patients were divided into vaccinated and unvaccinated groups according to vaccination status. Demographic and clinical data were collected. RESULTS: A total of 280 individuals (213 UC and 67 CD patients) were enrolled in the study. The unvaccinated and vaccinated groups of UC patients were comparable for basic characteristics, including age (t = - 0.8, p = 0.425), sex (χ2 = 0.980, p = 0.322), course of disease (z = - 0.513, p = 0.608), surgical conditions (χ2 = 1.042, p = 0.838), disease extent (χ2 = 4.853, p = 0.088), or baseline drug therapy (χ2 = 7.784, p = 0.064). In the subgroup of UC patients, there was no association between vaccination and disease activities, according to the medium disease activity scores for two groups: unvaccinated patients having scores (IQR) 1(2.75), 1(2), 1(2), and 1(2) at baseline, 1, 3, and 6 months, respectively, whereas vaccinated patients having scores (IQR) 1(2), 1(2), 1(2), and 1(2). Similar conclusions were also derived in the subgroup of CD patients. There were also no statistically significant differences in age (t = - 1.48, p = 0.144), sex (χ2 = 0.003, p = 0.957), course of disease (z = - 0.074, p = 0.941), surgical conditions (χ2 = 0.613, p = 0.594), localization (χ2 = 6.261, p = 0.199), or baseline drug therapy (χ2 = 5.881, p = 0.114) between 2 groups of CD patients. The medium disease activity scores (IQR) of the unvaccinated group at baseline, 1, 3, and 6 months were 1(4), 1(3), 1(3), and 1(3), respectively, whereas those of vaccinated group were 2.5(3.75), 2.5(3.75), 3(2), and 2(2), respectively. Overall, very few participants in this study described worsening IBD disease activity requiring a change or addition of medication. CONCLUSIONS: SARS-CoV-2 vaccine has no adverse effect on disease activity in IBD population. IBD patients should be recommended to receive SARS-CoV-2 vaccine in time.


Subject(s)
COVID-19 , Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Adult , Chlorocebus aethiops , Animals , Humans , Crohn Disease/drug therapy , Colitis, Ulcerative/drug therapy , COVID-19 Vaccines/therapeutic use , Vero Cells , COVID-19/prevention & control , SARS-CoV-2 , Inflammatory Bowel Diseases/drug therapy , China/epidemiology
12.
Environ Res ; 231(Pt 2): 116176, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37209980

ABSTRACT

Combining the comprehensive effects of temperature and humidity, this study applies a heat stress index to project future population exposure to high temperature and related health-risks over China under different climate change scenarios. Results show that the number of high temperature days, population exposure and their related health-risks will increase significantly in the future compared to the reference period (1985-2014), which is mainly caused by the change of >T99p (the wet bulb globe temperature >99th percentile derived from the reference period). The population effect is absolutely dominant in influencing the decrease in exposure to T90-95p (the wet bulb globe temperature is in the range of (90th, 95th]) and T95-99p (the wet bulb globe temperature is in the range of (95th, 99th]), and the climate effect is the most prominent contributor to the upsurge in exposure to > T99p in most areas. An additional 0.1 billion person-days increase in population exposure to T90-95p, T95-99p and >T99p in a given year is associated with the number of deaths by 1002 (95% CI: 570-1434), 2926 (95% CI: 1783-4069) and 2635 (95% CI: 1345-3925), respectively. Compared with the reference period, total exposure to high temperature under the SSP2-4.5 (SSP5-8.5) scenario will increase to 1.92 (2.01) times in the near-term (2021-2050) and 2.16 (2.35) times in the long-term (2071-2100), which will increase the number of people at heat risk by 1.2266 (95% CI: 0.6341-1.8192) [1.3575 (95% CI: 0.6926-2.0223)] and 1.5885 (95% CI: 0.7869-2.3902) [1.8901 (95% CI:0.9230-2.8572)] million, respectively. Significant geographic variations exist in the changes of exposure and related health-risks. The change is greatest in the southwest and south, whereas it is relatively small in the northeast and north. The findings provide several theoretical references for climate change adaptation.


Subject(s)
Climate Change , Hot Temperature , Humans , Temperature , China/epidemiology , Forecasting , Probability
13.
Dig Dis Sci ; 68(6): 2474-2481, 2023 06.
Article in English | MEDLINE | ID: mdl-36881197

ABSTRACT

BACKGROUND: Visceral adipose tissue (VAT) is related to SAP prognosis. As a depot of VAT, mesenteric adipose tissue (MAT) resides between pancreas and gut, which might affect SAP and the secondary intestinal injury. AIMS: To investigate the changes of MAT in SAP. METHODS: 24 SD rats were randomly divided into four groups. 18 rats in SAP group were euthanized in time gradients (6 h, 24 h, and 48 h after modeling) and the others in control group. Blood samples and tissues of pancreas, gut, and MAT were taken for analysis. RESULTS: Compared to the control group, SAP rats appeared MAT inflammation, presenting higher mRNA expression of TNF-α and IL-6 and lower IL-10, and histological changes after 6 h of modeling, which became worse over time. Flow cytometry showed that B lymphocytes increased in MAT after 24 h of SAP modeling and lasted up to 48 h, earlier than the changes of T lymphocytes and macrophages. The intestinal barrier integrity was damaged after 6 h of modeling, presenting lower mRNA and protein expression of ZO-1 and occludin, higher serum levels of LPS and DAO, with pathological changes, which gradually aggravated after 24 h and 48 h. SAP rats had higher serum levels of inflammatory indicators and revealed histological inflammation of pancreas, the severity of which increased with the passage of modeling time. CONCLUSION: MAT appeared inflammation in early-stage SAP, and became worse over time, with the same trend as the intestinal barrier injury and the severity of pancreatitis. B lymphocytes infiltrated early in MAT, which might promote the MAT inflammation.


Subject(s)
Intestinal Diseases , Pancreatitis , Rats , Animals , Pancreatitis/metabolism , Acute Disease , Intestinal Mucosa/metabolism , Rats, Sprague-Dawley , Inflammation/metabolism , Adipose Tissue/pathology , Patient Acuity , Intestinal Diseases/metabolism , RNA, Messenger/metabolism
14.
Neoplasma ; 70(5)2023 Oct.
Article in English | MEDLINE | ID: mdl-38053381

ABSTRACT

This study aimed to retrospectively evaluate the treatment strategies and possible prognostic factors in patients with brain metastases (BMs) from esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed 30 patients with BMs from ESCC who were treated at our center between November 2011 and January 2022. Clinicopathological characteristics and clinical outcomes were analyzed. The median follow-up time was 2 (range, 0.5-33) months. The median survival time after diagnosis of BMs was 2 months. The 1-year overall survival (OS) rate was 13.6%. The OS was better in patients with intracranial benefit. Multivariate analysis showed that local treatment of BMs influenced OS. The median survival with or without local treatment of BMs was 4 and 1 month, respectively. The median time interval between the diagnosis of the primary tumor and BMs was 11 (range, 1-156) months. Among these BMs, 55.6% of the BM occurred within the first year after diagnosis of the primary tumor, 66.7% in the first 2 years, and 85.2% in the first 3 years. The median time interval from lung metastasis to BMs was 3 months, from liver metastasis to BMs 3.5 months, and from bone metastasis to BMs 0.5 months. Local treatment of BMs was an independent prognostic factor for patients with BMs from ESCC. Earlier detection followed by an aggressive local therapeutic approach for BMs had a great influence on treatment outcomes as well as the long-term prognosis and quality of life for appropriately selected patients.


Subject(s)
Brain Neoplasms , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Retrospective Studies , Quality of Life , Prognosis , Brain Neoplasms/pathology
15.
Proc Natl Acad Sci U S A ; 117(34): 20753-20763, 2020 08 25.
Article in English | MEDLINE | ID: mdl-32759223

ABSTRACT

Fibrotic diseases remain a major cause of morbidity and mortality, yet there are few effective therapies. The underlying pathology of all fibrotic conditions is the activity of myofibroblasts. Using cells from freshly excised disease tissue from patients with Dupuytren's disease (DD), a localized fibrotic disorder of the palm, we sought to identify new therapeutic targets for fibrotic disease. We hypothesized that the persistent activity of myofibroblasts in fibrotic diseases might involve epigenetic modifications. Using a validated genetics-led target prioritization algorithm (Pi) of genome wide association studies (GWAS) data and a broad screen of epigenetic inhibitors, we found that the acetyltransferase CREBBP/EP300 is a major regulator of contractility and extracellular matrix production via control of H3K27 acetylation at the profibrotic genes, ACTA2 and COL1A1 Genomic analysis revealed that EP300 is highly enriched at enhancers associated with genes involved in multiple profibrotic pathways, and broad transcriptomic and proteomic profiling of CREBBP/EP300 inhibition by the chemical probe SGC-CBP30 identified collagen VI (Col VI) as a prominent downstream regulator of myofibroblast activity. Targeted Col VI knockdown results in significant decrease in profibrotic functions, including myofibroblast contractile force, extracellular matrix (ECM) production, chemotaxis, and wound healing. Further evidence for Col VI as a major determinant of fibrosis is its abundant expression within Dupuytren's nodules and also in the fibrotic foci of idiopathic pulmonary fibrosis (IPF). Thus, Col VI may represent a tractable therapeutic target across a range of fibrotic disorders.


Subject(s)
CREB-Binding Protein/genetics , Collagen Type VI/metabolism , E1A-Associated p300 Protein/metabolism , CREB-Binding Protein/metabolism , Cell Proliferation/drug effects , Collagen/metabolism , Collagen Type VI/physiology , E1A-Associated p300 Protein/genetics , Epigenesis, Genetic/genetics , Epigenomics/methods , Extracellular Matrix/metabolism , Fibroblasts/metabolism , Fibrosis/genetics , Fibrosis/metabolism , Genome-Wide Association Study , Humans , Myofibroblasts/metabolism , Myofibroblasts/physiology , Proteomics , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/metabolism
16.
Ann Intern Med ; 175(10): 1383-1391, 2022 10.
Article in English | MEDLINE | ID: mdl-36095315

ABSTRACT

BACKGROUND: With the widespread use of advanced imaging technology, adrenal tumors are increasingly being identified. OBJECTIVE: To investigate the prevalence and characteristics of adrenal tumors in an unselected screening population in China. DESIGN: Cross-sectional study. (ClinicalTrials.gov: NCT04682938). SETTING: A health examination center in China. PATIENTS: Adults having an annual checkup were invited to be screened for adrenal tumors by adrenal computed tomography. MEASUREMENTS: The participants with adrenal tumors had further evaluation for malignancy risk and adrenal function. RESULTS: A total of 25 356 participants were screened, 351 of whom were found to have adrenal tumors, for a prevalence of 1.4%. The prevalence increased with age, from 0.2% in participants aged 18 to 25 years to 3.2% in those older than 65 years. Among 351 participants with adrenal tumors, 337 were diagnosed with an adrenocortical adenoma, 14 with another benign nodule, and none with a malignant mass. In 212 participants with an adenoma who completed endocrine testing, 69.3% were diagnosed with a nonfunctioning adenoma, 18.9% with cortisol autonomy, 11.8% with primary aldosteronism, and none with pheochromocytoma. Proportions of nonfunctioning adenomas were similarly high in various age groups (72.2%, 67.8%, and 72.2% in those aged <46, 46 to 65, and ≥66 years, respectively). LIMITATION: Only 212 of 337 participants with an adrenocortical adenoma had endocrine testing. CONCLUSION: The prevalence of adrenal tumors in the general adult screening population is 1.4%, and most of these tumors are nonfunctioning regardless of patient age. Cortisol and aldosterone secretion are the main causes of functional adenomas. PRIMARY FUNDING SOURCE: National Key Research and Development Program of China and National Natural Science Foundation of China.


Subject(s)
Adenoma , Adrenal Gland Neoplasms , Adrenocortical Adenoma , Adenoma/diagnosis , Adolescent , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/epidemiology , Adult , Aldosterone , Cross-Sectional Studies , Humans , Hydrocortisone , Prevalence , Research , Young Adult
17.
J Craniofac Surg ; 34(4): e381-e383, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37262412

ABSTRACT

Mandibular asymmetry is among the most common facial anomalies. Traditionally, mandibular asymmetry with malocclusion has been treated with orthognathic surgery and genioplasty. However, routine genioplasty cannot achieve a satisfactory contour. Hence, this study presents a modified technique, himi-lengthening genioplasty, to resolve this matter. By combining this technique with orthognathic surgery, the authors successfully corrected mandibular asymmetry in 1-stage surgery, achieved ideal occlusion, and reconstructed the esthetic contour. No complications occurred during the 6-month follow-up period. Therefore, the authors recommend our modified surgical technique for its effectiveness, security, stability, and simplicity.


Subject(s)
Genioplasty , Orthognathic Surgical Procedures , Humans , Genioplasty/methods , Treatment Outcome , Esthetics, Dental , Mandible/surgery , Mandible/abnormalities , Orthognathic Surgical Procedures/methods , Facial Asymmetry/surgery
18.
J Sci Food Agric ; 103(11): 5432-5441, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37038905

ABSTRACT

BACKGROUND: In this study, the fermentation conditions of peony seed soy sauce (PSSS) koji were optimized by response surface method, and the quality components and antioxidant activity of PSSS were investigated at different low-salt solid-state fermentation stages. RESULTS: Results of response surface method showed that the optimal fermentation conditions were 460.6 g kg-1 water content, 48.6 h culture time, 31.5 °C culture temperature and ratio 2.1:1 (w/w) of peony seed meal:wheat bran, with the highest neutral protease activity (2193.78 U g-1 ) of PSSS koji. PSSS had the highest amino acid nitrogen (7.69 g L-1 ), salt-free soluble solids (185.26 g L-1 ), total free amino acids (49.03 g L-1 ), essential free amino acids (19.58 g L-1 ) and umami free amino acids (16.64 g L-1 ) at 20 days of fermentation. The highest total phenolics were 5.414 g gallic acid equivalent L-1 and total flavonoids 0.617 g rutin equivalent L-1 , as well as the highest DPPH radical scavenging activity (86.19%) and reducing power (0.8802, A700 ) of PSSS fermented at 30 days. Sensory evaluation showed that fermentation of 20 days and 25 days could produce a better taste and aroma of PSSS than 15 days and 30 days. CONCLUSION: PSSS had the highest quality components in the middle of fermentation (20 days) and the highest antioxidant activity in the late fermentation period (30 days). These results demonstrated that peony seed meal could be used to produce high-quality soy sauce with high antioxidant activity. © 2023 Society of Chemical Industry.


Subject(s)
Paeonia , Soy Foods , Fermentation , Antioxidants , Taste , Amino Acids , Amino Acids, Essential
19.
Int J Mol Sci ; 23(22)2022 Nov 15.
Article in English | MEDLINE | ID: mdl-36430550

ABSTRACT

Dye degradation is a key reaction in organic decomposition production through electron donor transferring. Palladium (Pd) is the best-known element for synthesis Pd-based catalyst, the surface status determines the scope of relative applications. Here we first prepare Pd-Cu alloy nanoparticles (NPs) by co-reduction of Cu(acac)2 (acac = acetylacetonate) and Pd(C5HF6O2)2 in the presence of sodium borohydride (NaBH4) and glutathione (GSH). The obtained Pd-Cu is about ~10 nm with super-hydrophilicity in aqueous mediums. The structural analysis clearly demonstrated the uniform distribution of Pd and Cu element. The colloidal solution keeps stability even during 30 days. Bimetallic Pd-Cu NPs shows biocompatibility in form of cell lines (IMEF, HACAT, and 239 T) exposed to colloidal solution (50 µg mL-1) for 2 days. It shows the catalytic multi-performance for dye degradation such as methyl orange (MO), rhodamine B (RhB), and methylene blue (MB), respectively. The as-synthesized nanoparticles showed one of the best multiple catalytic activities in the industrially important (electro)-catalytic reduction of 4-nitrophenol (4-NP) to corresponding amines with noticeable reduced reaction time and increased rate constant without the use of any large area support. In addition, it exhibits peroxidase-like activity in the 3, 3', 5, 5'-Tetramethylbenzidine (TMB) color test and exhibit obvious difference with previous individual metal materials. By treated with high intensity focused ultrasound filed (HIFU), Pd-Cu NPs might be recrystallized and decreased the diameters than before. The enhancement in catalytic performance is observed obviously. This work expedites rational design and synthesis of the high-hierarchy alloy catalyst for biological and environment-friendly agents.


Subject(s)
Metal Nanoparticles , Palladium , Palladium/chemistry , Alloys/chemistry , Metal Nanoparticles/chemistry , Catalysis , Copper/chemistry
20.
Entropy (Basel) ; 24(3)2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35327920

ABSTRACT

Characterizing the topology and random walk of a random network is difficult because the connections in the network are uncertain. We propose a class of the generalized weighted Koch network by replacing the triangles in the traditional Koch network with a graph Rs according to probability 0≤p≤1 and assign weight to the network. Then, we determine the range of several indicators that can characterize the topological properties of generalized weighted Koch networks by examining the two models under extreme conditions, p=0 and p=1, including average degree, degree distribution, clustering coefficient, diameter, and average weighted shortest path. In addition, we give a lower bound on the average trapping time (ATT) in the trapping problem of generalized weighted Koch networks and also reveal the linear, super-linear, and sub-linear relationships between ATT and the number of nodes in the network.

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