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1.
J Transl Med ; 22(1): 586, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902782

ABSTRACT

The prevalence of papillary thyroid cancer (PTC) has been rising in recent years. Despite its relatively low mortality, PTC frequently metastasizes to lymph nodes and often recurs, posing significant health and economic burdens. The role of iodine in the pathogenesis and advancement of thyroid cancer remains poorly understood. Circular RNAs (circRNAs) are recognized to function as competing endogenous RNAs (ceRNAs) that modulate gene expression and play a role in various cancer stages. Consequently, this research aimed to elucidate the mechanism by which circRNA influences the impact of iodine on PTC. Our research indicates that high iodine levels can exacerbate the malignancy of PTC via the circ_0004851/miR-296-3p/FGF11 axis. These insights into iodine's biological role in PTC and the association of circRNA with the disease could pave the way for novel biomarkers and potentially effective therapeutic strategies to mitigate PTC progression.


Subject(s)
Gene Expression Regulation, Neoplastic , Iodine , MicroRNAs , RNA, Circular , Thyroid Cancer, Papillary , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Humans , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Iodine/metabolism , Cell Line, Tumor , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Base Sequence
2.
Ann Surg Oncol ; 31(5): 2913-2924, 2024 May.
Article in English | MEDLINE | ID: mdl-38319516

ABSTRACT

BACKGROUND: Myosteatosis is correlated with poor prognosis in some malignancies. The creatinine-to-cystatin ratio (CCR) is revealed to predict gastric cancer prognosis. However, the prognostic abilities of CCR and the combination of CCR and myosteatosis in patients with pancreatic cancer (PC) who underwent radical surgery remains unclear. METHODS: The retrospective cohort study included 215 patients with PC who underwent radical surgery (January 2016-October 2021). Clinicopathological and serological data were collected on admission. Myosteatosis and other body composition indices were assessed by using computed tomography. The cutoff value of CCR was determined by using the Youden index. Risk factors responsible for poor overall survival (OS) and disease-free survival (DFS) were determined by the Cox proportional hazards model. RESULTS: The myosteatosis group included 104 patients (average age, 61.3 ± 9.1 years). The best cutoff value for CCR was 1.09. CCR ≤ 1.09 was an independent predictive biomarker inversely corelated with OS (P = 0.036). Myosteatosis was an independent risk factor associated with OS and DFS (P = 0.032 and P = 0.004, respectively). Patients with concomitant myosteatosis and CCR ≤ 1.09 had the worst OS (P = 0.016). CONCLUSIONS: Myosteatosis and CCR are prognostic biomarkers for survival in PC patients who underwent radical surgery. Patients with the coexistence of myosteatosis and CCR ≤ 1.09 deserve more attention.


Subject(s)
Creatinine , Cystatin C , Pancreatic Neoplasms , Aged , Humans , Middle Aged , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Prognosis , Retrospective Studies
3.
Cell Commun Signal ; 22(1): 45, 2024 01 17.
Article in English | MEDLINE | ID: mdl-38233864

ABSTRACT

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Lung Neoplasms/pathology , Mutation/genetics , Protein Kinase Inhibitors/pharmacology , Retinoblastoma Binding Proteins/genetics , Smad4 Protein/genetics , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Ubiquitin-Protein Ligases/genetics
4.
Dig Endosc ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39253819

ABSTRACT

OBJECTIVES: Endoscopic full-thickness resection (EFTR) for submucosal tumors (SMTs) has been technically challenging. This retrospective study aimed to evaluate the feasibility, safety, and efficacy of EFTR for upper gastrointestinal (GI) SMTs, including extraluminal lesions. METHODS: We retrospectively investigated 232 patients with SMTs who underwent EFTR from January 2014 to August 2023. Clinicopathologic characteristics, procedure-related parameters, adverse events (AEs), and follow-up outcomes were assessed in all patients. RESULTS: The en-bloc resection and en-bloc with R0 resection rates were 98.7% and 96.1%, respectively. The average endoscopic tumor size measured 17.2 ± 8.7 mm, ranging from 6 to 50 mm. The resection time and suture time were 49.0 ± 19.4 min and 22.5 ± 11.6 min, respectively. In all, 39 lesions (16.8%) exhibited predominantly extraluminal growth. Gastrointestinal stromal tumors (GISTs) were the predominant pathology, accounting for 78.4% of the cases. Twenty-one patients (9.1%) encountered complications, including pneumothorax (1/232, 0.43%), hydrothorax (1/232, 0.43%), localized peritonitis (3/232, 1.29%), and fever (16/232, 6.9%). Although the incidence of postoperative fever was notably higher in the predominantly extraluminal group (7/39, 17.9%) compared to the predominantly intraluminal group (9/193, 4.7%, P = 0.008), there were no significant differences in outcomes of the EFTR procedure. No instances of recurrence were observed during the mean follow-up period of 3.7 ± 2.3 years. CONCLUSION: EFTR was found to be feasible, safe, and effective for resecting upper GI SMTs, including lesions with predominantly extraluminal growth. Further validation in a prospective study is warranted.

5.
Anal Chem ; 94(27): 9775-9784, 2022 07 12.
Article in English | MEDLINE | ID: mdl-35759408

ABSTRACT

Near-infrared (NIR) photothermal transduction agents (PTAs) with large rigid π-extended and planar structures are prone to aggregate in a physiological environment where their emission is often quenched due to the strong intermolecular dipole-dipole or π-π interactions. This aggregation-caused quenching effect greatly impedes their applications in image-guided photothermal theranostics. Herein, we made an interesting finding that engineering a bioinspired protein corona (PC), once thermodynamically stabilized in preferred orientations on PTA nanoaggregates, can produce brilliant NIR fluorescence with a high quantum yield (∼6.2%) without compromising their photothermal properties. Both experimental data and computational modeling suggest that the mechanism of fluorescence enhancement is due to the high-affinity binding of nano-sized PTA to albumin, which regulates the molecular conformation and aggregation state of PTA. High spatial and temporal resolution imaging of albumin PC-coated PTA aggregates enables image-guided photothermal therapy for cancer cells in sentinel lymph nodes to remarkably inhibit pulmonary metastasis. Such a treatment combined with the surgical removal of the primary tumor can prolong animal survival, which is a promising candidate for clinical applications in the treatment of advanced metastatic cancers.


Subject(s)
Neoplasms , Protein Corona , Albumins/chemistry , Animals , Cell Line, Tumor , Fluorescence , Neoplasms/therapy , Optical Imaging , Phototherapy , Theranostic Nanomedicine/methods
6.
Hum Genomics ; 15(1): 38, 2021 06 29.
Article in English | MEDLINE | ID: mdl-34187569

ABSTRACT

BACKGROUND: Acute myeloid leukemia (AML) is recognized as a hematological neoplasm with heterogenetic cytology and short-term outcome. HCP5 has been proven to be related with the pathogenesis of AML. However, the underlying mechanism of HCP5 in AML remains unclear. METHODS: Clinical profiles of AML patients were downloaded from TCGA and GTEx databases. LncBase and TargetScan online tools were utilized to predict potential targets, and dual-luciferase reporter assay was performed to verify the association between miR-1291 and HCP5 or PIK3R5. Cell Counting Kit 8 and flow cytometry tests were implemented to evaluate the effects of HCP5/miR-1291/PIK3R5 axis in AML cells. Quantitative RT-PCR and Western blot were conducted to detect the expression levels of genes. RESULTS: HCP5 and PIK3R5 were significantly increased in AML tissue samples compared with healthy controls. HCP5 facilitated AML cells viability and inhibited apoptosis. There was a positive relationship between HCP5 and PIK3R5, but miR-1291 negatively regulated PIK3R5. Overexpression of PIK3R5 enhanced the promoting effect of HCP5 in the development of AML, while weakened the suppression of miR-1291 to AML progression. CONCLUSION: Our findings manifested that HCP5 was remarkably upregulated in AML and upregulated HCP5 promoted the malignant behaviors of AML cells by mediating miR-1291/PIK3R5 axis, which would provide a new insight for the treatment of AML.


Subject(s)
Leukemia, Myeloid, Acute/genetics , MicroRNAs/genetics , Phosphatidylinositol 3-Kinase/genetics , RNA, Long Noncoding/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Leukemic , Humans , Leukemia, Myeloid, Acute/pathology , Signal Transduction/genetics
7.
Med Sci Monit ; 28: e933942, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35231021

ABSTRACT

BACKGROUND This study retrospectively explored body composition changes and related factors in patients with ulcerative colitis (UC). MATERIAL AND METHODS Patients with UC and healthy individuals who served as the healthy control at the Affiliated Hospital of Qingdao University September 2017 to August 2018 were retrospectively analyzed. Clinical data and laboratory examination indexes were collected. The skeletal muscle area (SMA) of the third lumbar vertebra cross-section, the subcutaneous fat area (SFA), and the visceral fat area (VFA) at the umbilical level were measured by computed tomography (CT), and the skeletal muscle index (SMI) was calculated to evaluate the loss of muscle mass. RESULTS Data from a total of 80 patients (median age, 49.49 years; 44 [55%] men) with active UC in the UC group and 80 healthy people age- and sex-matched in the healthy control group were collected. The incidence of low SMI and malnutrition was remarkably higher in the UC group than in the healthy control group (P<0.05). Low SMI was observed in 62.5% of UC patients who had a normal body mass index. Based on classification by the Truelove and Witts' criteria, the prevalence of malnutrition in severe UC patients was remarkably higher than that in mild and moderate UC patients (P<0.05). Based on the disease extent, the prevalence of low SMI in E3 type UC was dramatically higher than that in E2 type (P=0.028). CONCLUSIONS Loss of muscle mass was related to disease extent in patients with UC. Loss of muscle mass is more likely to be associated with malnutrition.


Subject(s)
Body Composition/physiology , Colitis, Ulcerative/diagnosis , Malnutrition/epidemiology , Tomography, X-Ray Computed/methods , Aged , China/epidemiology , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/physiopathology , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies
8.
BMC Ophthalmol ; 22(1): 161, 2022 Apr 07.
Article in English | MEDLINE | ID: mdl-35392841

ABSTRACT

BACKGROUND: To evaluate the effects of 0.02% and 0.01% atropine eye drops on ocular and corneal astigmatism over 2 years. METHODS: A prospective clinic-controlled trail. The cohort study assessed 400 myopic children and divided them into three groups: 138 and 142 children were randomized to use either 0.02% or 0.01% atropine eye drops, respectively. They wore single-vision (SV) spectacles, with one drop of atropine applied to both eyes once nightly. Control children (n = 120) only wore SV spectacles. Spherical equivalent refractive errors (SER) and corneal curvature were measured every 4 months. The SER and corneal curvature were assessed by cycloplegic autorefraction and IOLMaster. Ocular and corneal astigmatism were calculated by Thibos vector analysis and then split into its power vector components, J0 (with-the-rule astigmatism) and J45 (oblique). RESULTS: After 2 years, the ocular astigmatism increased by -0.38 ± 0.29 D, -0.47 ± 0.38 D, -0.41 ± 0.35 D in the 0.02%, 0.01% atropine groups and control group, respectively (p = 0.15). The corresponding corneal astigmatism increased by -0.20 ± 0.34 D, -0.28 ± 0.35 D and -0.26 ± 0.26 D (p = 0.18). The ocular astigmatism J0 increased by 0.19 ± 0.28 D, 0.22 ± 0.36 D, 0.18 ± 0.31 D in the 0.02% atropine, 0.01% atropine and control groups, respectively (p = 0.65). The corresponding corneal astigmatism J0 increased by -0.05 ± 0.34 D, -0.11 ± 0.37 D and -0.13 ± 0.30 D (p = 0.23). There was a small but significant increase in ocular astigmatism (including J0) (all P < 0.05), but there were no changes in the ocular astigmatism J45 and corneal astigmatism (including J0 and J45) in the three groups over time (all p > 0.05). However, there were no significant differences in the changes in ocular astigmatism (including J0) among the three groups. CONCLUSIONS: Treatment with 0.02% and 0.01% atropine had no clinically significant effect on ocular and corneal astigmatism over 2 years. TRIAL REGISTRATION: The First Affiliated Hospital of Zhengzhou University, ChiCTR-IPD-16008844 . Registered 14/07/2016.


Subject(s)
Astigmatism , Corneal Diseases , Astigmatism/drug therapy , Atropine/therapeutic use , Child , Cohort Studies , Cornea , Humans , Ophthalmic Solutions , Prospective Studies , Refraction, Ocular
9.
J Clin Lab Anal ; 36(5): e24433, 2022 May.
Article in English | MEDLINE | ID: mdl-35435260

ABSTRACT

OBJECTIVE: Patients with liver cirrhosis (LC) commonly exhibit hypercoagulability and tend to develop thrombosis. Neutrophil extracellular traps (NETs) are associated with a variety of thrombotic conditions, but their possible value in portal vein thrombosis (PVT) is not known. We assessed whether NETs promote thrombosis and contribute to the procoagulant state in patients with LC. METHODS: The circulating levels of NETs markers (myeloperoxidase, neutrophil elastase, citrullinated histone H3) were measured in 72 patients (median age, 55 years; 48 [66.7%] men) with LC from September 2020 to February 2021. Then they were divided into two groups: patients with or without PVT. NETs procoagulant activity was assessed based on thrombin-antithrombin complex (TAT complex) and Factor X. The levels of plasma markers were determined by ELISA. RESULTS: There were 28 patients with PVT and 44 patients without PVT. The levels of NETs markers and hypercoagulability markers in the plasma of cirrhosis patients with PVT were significantly higher than those of cirrhosis patients without PVT (p < 0.05). Additionally, the levels of the NETs markers correlated with TAT complex and Factor X (Spearman correlation rho >0.73, p < 0.0001). CONCLUSIONS: Neutrophil extracellular traps seem to enhance procoagulant activity in LC patients with PVT; thus, they may be a practical predictor of PVT as well as a rapid and easy-to-use diagnostic and treatment guide for PVT in patients with cirrhosis.


Subject(s)
Extracellular Traps , Thrombophilia , Thrombosis , Venous Thrombosis , Factor X , Female , Humans , Liver Cirrhosis , Male , Middle Aged , Portal Vein/pathology , Venous Thrombosis/complications
10.
Yi Chuan ; 44(12): 1141-1147, 2022 Dec 20.
Article in English | MEDLINE | ID: mdl-36927559

ABSTRACT

Recently, several pedigree-based studies have shown that abnormal replication of an enhancer element regulatory region in the downstream of the bone morphogenetic protein 2 (BMP2) gene is the cause of brachydactyly type A2 (BDA2). However, the exact molecular function of this regulatory region is unclear, and even conflicting results have emerged. In this study, based on bioinformatics analysis, we amplified target fragments of different lengths in this regulatory region by PCR technology, including a highly conserved 2.1 kb core sequence and 3 fragments that can completely cover the core 2.1 kb fragment. Then, the gene recombination vectors were constructed, and the biological function of these fragments was analyzed by the dual-luciferase reporter gene technology system. We found that the highly conserved 2.1 kb fragment did not have enhancer activity, while all of three truncated fragments showed strong enhancer activity. The results suggest that the expression regulation mode of the BMP2 gene is very complex. For the downstream regulatory region, selecting fragments of different lengths may have different effects on the regulation of BMP2 expression, which may due to the fragments with different lengths carrying different regulatory elements in the number of types. In summary, this study revealed the complexity of BMP2 gene regulatory elements, and provided new clues and directions for the subsequent in-depth exploration of the molecular pathogenic mechanism of BDA2.


Subject(s)
Brachydactyly , Regulatory Sequences, Nucleic Acid , Humans , Regulatory Sequences, Nucleic Acid/genetics , Bone Morphogenetic Protein 2/genetics
11.
J Minim Access Surg ; 18(4): 489-496, 2022.
Article in English | MEDLINE | ID: mdl-35915535

ABSTRACT

Background: Ultrasound (US)- or computed tomography-guided drainage for abdominal abscess is currently the first-line options for drainage, but both options have disadvantages. Patients without adequate windows for drainage mostly undergo surgical drainage. However, surgical drainage is invasive and expensive. Endoscopic US (EUS)-guided drainage is a minimally invasive alternative for abdominal abscess, but there is less consensus on its efficacy, safety and complications. This meta-analysis aims to evaluate EUS-guided drainage for abdominal abscess. Materials and Methods: We retrieved relevant papers on EUS-guided drainage for abdominal abscess from the PubMed, Cochrane Library, Web of Science and EMBASE databases. Each paper was reviewed, and data were extracted. We used R software version 3.6.3 to perform the meta-analysis. Fixed effects models were used for merging data. Results: A total of 11 papers met the inclusion criteria, with a total sample population of 264 patients. The meta-analysis showed that the pooled clinical success rate was 90% (95% confidence interval [CI], 0.85-0.95), the technical success rate was 99% (95% CI, 0.97-1.00) and the recurrence rate was 1% (95% CI, 0.00-0.03). Three studies reported the complications, including perforation, bleeding and stent migration; none of the other eight studies reported complications. There were no significant differences between subgroups. There was no publication bias in either the clinical or the technical success rates. Conclusions: This meta-analysis showed that EUS-guided drainage for abdominal abscess was effective and safe, with an excellent technical success rate. In addition, EUS-guided drainage could be used for abscesses with complex anatomy. Nevertheless, complications and stent type should be considered.

12.
Eur J Nutr ; 60(4): 2217-2230, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33104864

ABSTRACT

PURPOSE: Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. METHODS: KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. RESULTS: Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. CONCLUSIONS: Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.


Subject(s)
Gastrointestinal Microbiome , Hyperuricemia , Animals , Dietary Supplements , Hyperuricemia/drug therapy , Inulin , Mice , Mice, Knockout
13.
Chem Biodivers ; 18(6): e2100089, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33893719

ABSTRACT

A novel alkali-soluble polysaccharide (AASP) was isolated from Angelica sinensis (Oliv.) Diels under aqueous alkali treatment, and its structural characterization and antitumor activity in Vivo were evaluated in present study. Results of HPGPC and IC revealed that AASP was a neutral polysaccharide containing Ara, Gal and Glc in the mole ratio of 1.00 : 2.26 : 24.43, with the average molecular weight of 4.7 kDa. Periodate oxidation, Smith degradation, methylation, FT-IR, and NMR analyses further demonstrated that a preliminary structure of AASP was proposed as follows: (1→3)-linked arabinose, (1→6)-linked galactose, and (1→), (1→4), (1→6), (1→3,6)-linked glucose with α- and ß-configuration. In Vivo antitumor assays, AASP exhibited prominent antitumor effects on H22 hepatoma cells with an inhibitory ratio of 48.57 % and effectively protected thymuses and spleens of tumor-bearing mice. Besides, AASP displayed a proliferation stimulating activity of immunocytes (splenocytes, peritoneal macrophages and natural killer cells), and an auxo-action for cytokines release (TNF-α, IL-2 and IFN-γ), leading to the apoptosis of H22 solid tumors cells via G0/G1 phase arrested. The above data demonstrated that AASP holds great application potential to be a safe and effective antitumor supplement in the future.


Subject(s)
Alkalies/chemistry , Angelica sinensis/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Polysaccharides/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Drug Screening Assays, Antitumor , Female , Humans , Liver Neoplasms, Experimental/drug therapy , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms, Experimental/pathology , Mice , Mice, Inbred BALB C , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Solubility
14.
J Cell Mol Med ; 24(3): 2319-2329, 2020 02.
Article in English | MEDLINE | ID: mdl-31880857

ABSTRACT

Cardiac fibrosis is a key factor to determine the prognosis in patient with myocardial infarction (MI). The aim of this study is to investigate whether the transcriptional factor paired-related homeobox 2 (Prrx2) regulates Wnt5a gene expression and the role in myocardial fibrosis following MI. The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodelling was assessed by measuring interstitial fibrosis performed with Masson staining. Cell differentiation was examined by analysis the expression of alpha-smooth muscle actin (α-SMA). Both Prrx2 and Wnt5a gene expressions were up-regulated in mice following MI, accompanied with increased mRNA and protein levels of α-SMA, collagen I and collagen III, compared to mice with sham surgery. Adenovirus-mediated gene knock down of Prrx2 increased survival rate, alleviated cardiac fibrosis, decreased infarction sizes and improved cardiac functions in mice with MI. Importantly, inhibition of Prrx2 suppressed ischaemia-induced Wnt5a gene expression and Wnt5a signalling. In cultured cardiac fibroblasts, TGF-ß increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. Further, overexpression of Prrx2 or Wnt5a mirrored the effects of TGF-ß on cell differentiations of cardiac fibroblasts. Gene silence of Wnt5a also ablated cell differentiations induced by Prrx2 overexpression in cardiac fibroblasts. Mechanically, Prrx2 was able to bind with Wnt5a gene promoter to up-regulate Wnt5a gene expression. In conclusions, targeting Prrx2-Wnt5a signalling should be considered to improve cardiac remodelling in patients with ischaemic heart diseases.


Subject(s)
Fibrosis/genetics , Homeodomain Proteins/genetics , Myocardial Infarction/genetics , Up-Regulation/genetics , Wnt-5a Protein/genetics , Animals , Cell Differentiation/genetics , Collagen Type I/genetics , Collagen Type III/genetics , Fibroblasts/pathology , Gene Expression Regulation/genetics , Heart/physiology , Male , Mice , Myocardial Infarction/pathology , Myocardium/pathology , Myofibroblasts/pathology , Promoter Regions, Genetic/genetics , Signal Transduction/genetics , Transforming Growth Factor beta1/genetics
15.
Biochem Biophys Res Commun ; 529(4): 977-983, 2020 09 03.
Article in English | MEDLINE | ID: mdl-32819608

ABSTRACT

Krüppel-like factors (KLFs) are transcription factors that control the expression of downstream genes. The role of KLFs has been reported in cancers. KLF16 promotes the proliferation of gastric cancer cells by upregulating p21, while suppresses the tumorigenesis of glioma through targeting TFAM. The function of KLF16 is controversial in cancer development. In this study, we aimed to investigate the role of KLF16 in retinoblastoma (RB). KLF16 was highly expressed in RB tissues and cells. Overexpression of KLF16 promoted the proliferation, growth and migration of RB cells. By contrast, KLF16 interference showed opposite effects. Cell cycle arrest and apoptosis were induced or repressed by KLF16 knockdown or overexpression, respectively. Mechanistically, BCL2 like 15 (BCL2L15), an apoptosis gene, was negatively regulated by KLF16. Luciferase reporter and ChIP assay showed that KLF16 transcriptionally repressed the expression of BCL2L15 by binding to its promoter. BCL2L15 was lowly expressed in RB tissues. Additionally, overexpression of BCL2L15 inhibited the proliferation and increased the apoptosis in RB cells. Our study identifies that KLF16 contributes to RB cell proliferation and migration by negatively regulating BCL2L15.


Subject(s)
Gene Expression Regulation, Neoplastic , Kruppel-Like Transcription Factors/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Retinal Neoplasms/genetics , Retinal Pigment Epithelium/metabolism , Retinoblastoma/genetics , Apoptosis/genetics , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial Cells/metabolism , Epithelial Cells/pathology , Genes, Reporter , Humans , Kruppel-Like Transcription Factors/antagonists & inhibitors , Kruppel-Like Transcription Factors/metabolism , Luciferases/genetics , Luciferases/metabolism , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Retinal Neoplasms/metabolism , Retinal Neoplasms/pathology , Retinal Pigment Epithelium/pathology , Retinoblastoma/metabolism , Retinoblastoma/pathology , Signal Transduction , Transcription, Genetic
16.
J Anat ; 237(5): 933-940, 2020 11.
Article in English | MEDLINE | ID: mdl-32515838

ABSTRACT

The peripheral nervous system lacks lymphatic vessels and is protected by the blood-nerve barrier, which prevents lymphocytes and antibodies from entering the neural parenchyma. Peripheral nerve injury results in degeneration of the distal nerve and myelin degeneration causes macrophage aggregation, T lymphocyte infiltration, major histocompatibility complex class II antigen expression, and immunoglobulin G deposition in the nerve membrane, which together result in nerve edema and therefore affect nerve regeneration. In the present paper, we show myelin expression was absent from the sciatic nerve at 7 days after injury, and the expression levels of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and Prospero Homeobox 1 (Prox1) were significantly increased in the sciatic nerve at 7 days after injury. The lymphatic vessels were distributed around the myelin sheath and co-localized with lymphatic endothelial cells. Prox1 induces the formation of new lymphatic vessels, which play important roles in the elimination of tissue edema as well as in morphological and functional restoration of the damaged nerve. This study provides evidence of the involvement of new lymphatic vessels in nerve repair after sciatic nerve injury.


Subject(s)
Homeodomain Proteins/metabolism , Lymphangiogenesis , Nerve Regeneration , Peripheral Nerve Injuries/metabolism , Sciatic Nerve/injuries , Tumor Suppressor Proteins/metabolism , Animals , Disease Models, Animal , Membrane Transport Proteins/metabolism , Mice , Myelin Sheath/metabolism , Nerve Crush , Peripheral Nerve Injuries/pathology , Random Allocation , Sciatic Nerve/metabolism , Sciatic Nerve/pathology
17.
Opt Express ; 28(5): 7565-7575, 2020 Mar 02.
Article in English | MEDLINE | ID: mdl-32225981

ABSTRACT

Terahertz (THz) waves can be generated by the nonlinear interaction between ultrashort laser pulses and air. The semiclassical photocurrent model is widely used. It is simple, but neglects the quantum effects. Some theoretical works are based on solving the time-dependent Schrödinger equation. However, it meets the difficulty of prohibitively large boxes in long-time evolution. Here we adopted the wave-function splitting algorithm to fully contain the information of photoelectrons. The contributions of the excited states and interference effects in electron wavepackets to THz radiation are studied numerically. We also theoretically investigated the THz generation from nitrogen molecules in a biased electric field. It is found that the THz yield enhancement as a function of the static field strength in experiments can be reproduced well by our method. In addition, the restriction of wavelength and phase difference in the two-color laser fields is less strict in the presence of the static field.

18.
Zhongguo Zhong Yao Za Zhi ; 45(20): 4949-4956, 2020 Oct.
Article in Zh | MEDLINE | ID: mdl-33350268

ABSTRACT

Dioscoreae Nipponicae Rhizoma, the dried rhizoma of Dioscorea nipponica, has been widely used in traditional Chinese medicines. According to the different of the growth and cultivation patterns, Dioscoreae Nipponicae Rhizoma can be divided into two species, the wild Dioscoreae Nipponicae Rhizoma and the cultivated Dioscoreae Nipponicae Rhizoma. In this paper, an accurate and reliable fingerprint of Dioscoreae Nipponicae Rhizoma was established based on HPLC coupled with evaporative light scattering detector(ELSD). A total of 6 common peaks were marked, and the similarity of the Dioscoreae Nipponicae Rhizoma samples was above 0.950. The results indicated that the established fingerprint could be used for quality evaluation of Dioscoreae Nipponicae Rhizoma. Moreover, an HPLC coupled with ELSD method was developed for simultaneous quantitative analysis of six steroidal saponins, including protodioscin, protogracillin, methyl protodioscin, pseudoprotodioscin, dioscin and gracillin in wild Dioscoreae Nipponicae Rhizoma and cultivated Dioscoreae Nipponicae Rhizoma samples. Furthermore, chemometrics analysis such as principal component analysis and partial least squares discriminant analysis were performed to compare and discriminate wild Dioscoreae Nipponicae Rhizoma and cultivated Dioscoreae Nipponicae Rhizoma samples based on the quantitative data. The results indicated that the contents of steroidal saponins were notably different between the wild and cultivated Dioscoreae Nipponicae Rhizoma, and protodioscin and protogracillin were significant to effectively discriminate the wild and cultivated Dioscoreae Nipponicae Rhizoma samples, and these two compounds could be recognized as chemical markers. In conclusion, this present study might provide useful data and acceptable analysis method for identification and quality evaluation of Dioscoreae Nipponicae Rhizoma.


Subject(s)
Dioscorea , Drugs, Chinese Herbal , Chromatography, High Pressure Liquid , Quality Control , Rhizome
20.
Int J Mol Sci ; 20(18)2019 Sep 11.
Article in English | MEDLINE | ID: mdl-31514282

ABSTRACT

The development of floral organs plays a vital role in plant reproduction. In our research, the APETALA3 (AP3) promoter-transgenic lines showed abnormal developmental phenotypes in stamens and petals. The aim of this study is to understand the molecular mechanisms of the morphological defects in transgenic plants. By performing transgenic analysis, it was found that the AP3-promoted genes and the vector had no relation to the morphological defects. Then, we performed the expression analysis of the class A, B, and C genes. A dramatic reduction of transcript levels of class B genes (AP3 and PISTILLATA) was observed. Additionally, we also analyzed the methylation of the promoters of class B genes and found that the promoter of AP3 was hypermethylated. Furthermore, combining mutations in rdr2-2, drm1/2, and nrpd1b-11 with the AP3-silencing lines rescued the abnormal development of stamens and petals. The expression of AP3 was reactivated and the methylation level of AP3 promoter was also reduced in RdDM-defective AP3-silencing lines. Our results showed that the RdDM pathway contributed to the transcriptional silencing in the transgenic AP3-silencing lines. Moreover, the results revealed that fact that the exogenous fragment of a promoter could trigger the methylation of homologous endogenous sequences, which may be ubiquitous in transgenic plants.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , DNA Methylation/genetics , Gene Silencing , MADS Domain Proteins/genetics , Promoter Regions, Genetic , RNA, Plant/metabolism , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , Genetic Complementation Test , MADS Domain Proteins/metabolism , Phenotype , Plants, Genetically Modified , RNA, Plant/genetics
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