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Cellular and Molecular Biology... Feb 2022Gallbladder cancer is one of the gastrointestinal tumors with an extremely poor prognosis. Its incidence rate is gradually increasing worldwide, and the rate of radical...
Gallbladder cancer is one of the gastrointestinal tumors with an extremely poor prognosis. Its incidence rate is gradually increasing worldwide, and the rate of radical resection surgery is extremely low. Not sensitive to radiotherapy and chemotherapy, with a very poor prognosis. This study aimed to investigate whether the recombinant mouse angiostatin gene transfected anti-angiogenic gallbladder cancer cells can express angiostatin protein with the activity of inhibiting the growth of vascular endothelial cells and the inhibitory effect on the growth of gallbladder cancer. The recombinant mouse angiostatin gene eukaryotic expression plasmid was transfected into the gallbladder cancer cell line by applying liposome LIPOFECTAMINE 2000, and its activity was detected by vascular endothelial cell proliferation analysis. The results show that angiostatin can inhibit the growth of transplanted gallbladder cancer, and as the number of injections increases, the inhibition rate of gallbladder cancer growth also increases. At the end of the experiment, the total inhibition rate of gallbladder cancer growth reached 95% 5%, 20%, 30%, 40% gradually increase. Therefore, angiostatin has potential clinical application value in gene therapy of gallbladder cancer.
Topics: Angiostatins; Animals; Cell Proliferation; Endothelial Cells; Gallbladder Neoplasms; Genetic Therapy; Mice; Peptide Fragments
PubMed: 35818206
DOI: 10.14715/cmb/2021.67.6.16 -
Translational Psychiatry May 2022Angiostatin, an endogenous angiogenesis inhibitor generated by the proteolytic cleavage of plasminogen, was recently reported to contribute to the development of...
Angiostatin, an endogenous angiogenesis inhibitor generated by the proteolytic cleavage of plasminogen, was recently reported to contribute to the development of Alzheimer's disease (AD). However, whether there are pathological changes in angiostatin levels in individuals with AD dementia is unclear, and whether plasma angiostatin has a relationship with major AD pathological processes and cognitive impairment remains unknown. To examine plasma angiostatin levels in patients with AD dementia and investigate the associations of angiostatin with blood and cerebrospinal fluid (CSF) AD biomarkers, we conducted a cross-sectional study including 35 cognitively normal control (CN) subjects and 59 PiB-PET-positive AD dementia patients. We found that plasma angiostatin levels were decreased in AD dementia patients compared to CN subjects. Plasma angiostatin levels were negatively correlated with plasma Aβ42 and Aβ40 levels in AD dementia patients and positively correlated with CSF total tau (t-tau) levels and t-tau/Aβ42 in AD dementia patients with APOE-ε4. In addition, plasma angiostatin levels had the potential to distinguish AD from CN. These findings suggest a link between angiostatin and AD pathogenesis and imply that angiostatin might be a potential diagnostic biomarker for AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Angiostatins; Biomarkers; Cognitive Dysfunction; Cross-Sectional Studies; Humans; Peptide Fragments; tau Proteins
PubMed: 35538065
DOI: 10.1038/s41398-022-01962-6 -
Journal of Cancer 2022Tranexamic acid (TA) has been reported to exhibit antitumor effects in various mouse models of cancer. However, the mechanism underlying its antitumor effects against...
Tranexamic acid (TA) has been reported to exhibit antitumor effects in various mouse models of cancer. However, the mechanism underlying its antitumor effects against endometrial cancer remains to be elucidated. This study was aimed at investigating the efficacy of TA against chronic inflammation-associated endometrial cancer induced by -methyl--nitrosourea (MNU) and estradiol in a mouse model. After cancer induction, the mice were administered TA (12 mg/kg) three times weekly during the experimental period. The endometrial cancer development induced by MNU and estradiol was ameliorated by TA administration. Furthermore, TA treatment suppressed the levels of carbohydrate antigen 125, interleukin-6, and tumor necrosis factor-α in the plasma. The level of plasminogen, known as a TA target, increased in endometrial cancer and was further increased by TA treatment. On the other hand, plasmin levels increased in the model mice but decreased after TA treatment. Furthermore, the macrophage counts and the levels of matrix metalloproteinase (MMP)-12 and angiostatin in tumor cells in the uterus increased compared to the corresponding values in the control group and further increased upon TA treatment. The results of our study indicate that TA ameliorated the endometrial cancer induced by MNU and estradiol by regulating the macrophage/MMP-12/plasminogen/angiostatin signal transmission pathway.
PubMed: 35371322
DOI: 10.7150/jca.68169 -
Arthritis & Rheumatology (Hoboken, N.J.) Jul 2022As no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), we undertook this study to execute a broad screen of NPSLE...
OBJECTIVE
As no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), we undertook this study to execute a broad screen of NPSLE cerebrospinal fluid (CSF) using an aptamer-based platform.
METHODS
CSF was obtained from NPSLE patients and subjected to proteomic assay using the aptamer-based screen. Potential biomarkers were identified and validated in independent NPSLE cohorts in comparison to other neurologic diseases.
RESULTS
Forty proteins out of the 1,129 screened were found to be elevated in NPSLE CSF. Based on enzyme-linked immunosorbent assay validation, CSF levels of angiostatin, α2-macroglobulin, DAN, fibronectin, hepatocellular carcinoma clone 1, IgM, lipocalin 2, macrophage colony-stimulating factor (M-CSF), and serine protease inhibitor G1 were significantly elevated in a predominantly White NPSLE cohort (n = 24), compared to patients with other neurologic diseases (n = 54), with CSF IgM (area under the curve [AUC] 0.95) and M-CSF (AUC 0.91) being the most discriminatory proteins. In a second Hong Kong-based NPSLE cohort, CSF IgM (AUC 0.78) and lipocalin 2 (AUC 0.85) were the most discriminatory proteins. Several CSF proteins exhibited high diagnostic specificity for NPSLE in both cohorts. Elevated CSF complement C3 was associated with an acute confusional state. Eleven molecules elevated in NPSLE CSF exhibited concordant elevation in the choroid plexus, suggesting shared origins.
CONCLUSION
Lipocalin 2, M-CSF, IgM, and complement C3 emerge as promising CSF biomarkers of NPSLE with diagnostic potential.
Topics: Biomarkers; Choroid Plexus; Complement C3; Humans; Immunoglobulin M; Lipocalin-2; Lupus Vasculitis, Central Nervous System; Macrophage Colony-Stimulating Factor; Proteomics; Transcriptome
PubMed: 35099126
DOI: 10.1002/art.42080 -
Immune Network Dec 2021Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021.... (Review)
Review
Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.
PubMed: 35036025
DOI: 10.4110/in.2021.21.e38 -
Cellular and Molecular Life Sciences :... Jan 2022In the cartilage matrix, complex interactions occur between angiogenic and anti-angiogenic components, growth factors, and environmental stressors to maintain a proper... (Review)
Review
In the cartilage matrix, complex interactions occur between angiogenic and anti-angiogenic components, growth factors, and environmental stressors to maintain a proper cartilage phenotype that allows for effective load bearing and force distribution. However, as seen in both degenerative disease and tissue engineering, cartilage can lose its vascular resistance. This vascularization then leads to matrix breakdown, chondrocyte apoptosis, and ossification. Research has shown that articular cartilage inflammation leads to compromised joint function and decreased clinical potential for regeneration. Unfortunately, few articles comprehensively summarize what we have learned from previous investigations. In this review, we summarize our current understanding of the factors that stabilize chondrocytes to prevent terminal differentiation and applications of these factors to rescue the cartilage phenotype during cartilage engineering and osteoarthritis treatment. Inhibiting vascularization will allow for enhanced phenotypic stability so that we are able to develop more stable implants for cartilage repair and regeneration.
Topics: Aggrecans; Angiogenesis Inhibitors; Angiostatins; Animals; Apoptosis; Cartilage; Chondrocytes; Cytokines; Endostatins; Humans; Inflammation; Low Density Lipoprotein Receptor-Related Protein-1; Mice; Osteoarthritis; Osteogenesis; Regeneration; Serine Proteinase Inhibitors; Stem Cells; Thrombospondins; Tissue Engineering; Tissue Extracts; Troponin I; Vascular Endothelial Growth Factor A
PubMed: 35029764
DOI: 10.1007/s00018-021-04105-0 -
Biological & Pharmaceutical Bulletin Mar 2022Anti-angiogenic gene therapy is a promising strategy in treating cancer. Endostatin and angiostatin are widely used in tumor anti-angiogenesis therapy. Our previous...
Anti-angiogenic gene therapy is a promising strategy in treating cancer. Endostatin and angiostatin are widely used in tumor anti-angiogenesis therapy. Our previous studies have shown that the BDS-hEA, a baculovirus long-term expressing the fusion protein of human endostatin and angiostatin, has a favorable effect in inhibiting the growth and angiogenesis of hepatocellular carcinoma. The purpose of this study was to further investigate its synergistic antitumor efficiency in combination with low-dose chemotherapeutic gemcitabine (GEM) on the subcutaneous hepatocellular carcinoma xenograft model in nude mice. The results showed that the combined group significantly inhibited (p < 0.05 or p < 0.01 or p < 0.001) the growth of tumor weight and volume, reduced the expression of ki67 (cell proliferation marker), CD31 (angiogenic marker) and Matrix metalloproteinase 9 (MMP-9, tumor invasion and metastasis marker) and increased the apoptosis of tumor cells compared with the monotherapy and control groups, respectively. Synergistic index results showed that BDS-hEA combined with GEM had a synergistic effect in inhibiting tumor volume, proliferation, microvessel density, metastasis and promoting tumor apoptosis. Furthermore, there were no metastatic nodules and obvious pathological changes in liver tissue of the combined group, and the serum liver function indicators aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-BIL), alkaline phosphatase (ALP) and glutamyl transpeptidase (GGT) were significantly reduced (p < 0.05 or p < 0.01 or p < 0.001) in the BDS-hEA or GEM groups compared with the control group. Notably, the combined therapy showed lower levels of liver function indicators than the GEM group. These data support the view that the combination of BDS-hEA and GEM has a synergistic anti-tumor properties and can reduce the damage of liver to certain extent.
Topics: Angiogenesis Inhibitors; Angiostatins; Animals; Baculoviridae; Carcinoma, Hepatocellular; Deoxycytidine; Endostatins; Humans; Liver Neoplasms; Mice; Mice, Nude; Gemcitabine
PubMed: 34937830
DOI: 10.1248/bpb.b21-00857 -
Molecules (Basel, Switzerland) Nov 2021Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of...
Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich's mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2/STAT3 signaling and the possible impact on tumor angiogenesis. The biological study was supported by molecular docking and bioinformatic predictions for the possible effect of nifuroxazide on this signaling pathway. Female albino mice were injected with Ehrlich carcinoma cells to produce Ehrlich's solid tumors (ESTs). The experimental groups were as follows: EST control, EST + nifuroxazide (5 mg/kg), and EST + nifuroxazide (10 mg/kg). Nifuroxazide was found to reduce tumor masses (730.83 ± 73.19 and 381.42 ± 109.69 mg vs. 1099.5 ± 310.83) and lessen tumor pathologies. Furthermore, nifuroxazide downregulated IL-6, TNF-α, NFk-β, angiostatin, and Jak2 proteins, and it also reduced tumoral VEGF, as indicated by ELISA and immunohistochemical analysis. Furthermore, nifuroxazide dose-dependently downregulated STAT3 phosphorylation (60% and 30% reductions, respectively). Collectively, the current experiment shed light on the antitumor activity of nifuroxazide against mammary solid carcinoma grown in vivo. The antitumor activity was at least partly mediated by inhibition of IL-6/Jak2/STAT3 signaling that affected angiogenesis (low VEGF and high angiostatin) in the EST. Therefore, nifuroxazide might be a promising antitumor medication if appropriate human studies will be conducted.
Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Female; Hydroxybenzoates; Interleukin-6; Janus Kinase 2; Mice; Molecular Docking Simulation; Neovascularization, Pathologic; Nitrofurans; STAT3 Transcription Factor; Signal Transduction
PubMed: 34833950
DOI: 10.3390/molecules26226858 -
American Journal of Translational... 2021Dyslipidemia aggravates kidney injury distal to atherosclerotic renal artery stenosis (ARAS). Besides dyslipidemia, metabolic syndrome (MetS) also involves development...
BACKGROUND
Dyslipidemia aggravates kidney injury distal to atherosclerotic renal artery stenosis (ARAS). Besides dyslipidemia, metabolic syndrome (MetS) also involves development of obesity and insulin-resistance (IR). We hypothesized that concurrent obesity and IR magnify swine stenotic-kidney damage beyond dyslipidemia.
METHODS
Pigs with unilateral RAS were studied after 16 weeks of atherogenic diets without (ARAS) or with (MetS + RAS) development of obesity/IR (n=6 each). Additional pigs on normal diet served as normal or non-dyslipidemic RAS controls (n=6 each). Stenotic-kidney renal blood flow (RBF), glomerular filtration rate (GFR), and microvascular architecture were studied using CT, and oxygenation was studied using blood oxygen level-dependent magnetic-resonance-imaging. We further compared kidney adiposity, oxidative stress, inflammation, apoptosis, fibrosis, and systemic levels of oxidative and inflammatory cytokines.
RESULTS
ARAS and MetS + RAS developed hypertension and dyslipidemia, and MetS + RAS also developed obesity and IR. RBF and GFR were similarly decreased in all post-stenotic pig kidneys compared to normal pig kidneys, yet MetS + RAS aggravated and expanded medullary hypoxia and microvascular loss. RAS and ARAS increased systemic levels of tumor necrosis factor (TNF)-α, which were further elevated in MetS + RAS. Renal oxidative stress and TNF-α expression increased in ARAS and further in MetS + RAS, which also upregulated expression of anti-angiogenic angiostatin, and magnified apoptosis, tubular injury, and fibrosis.
CONCLUSION
Beyond dyslipidemia, obesity and insulin-resistance aggravate damage in the post-stenotic kidney in MetS, despite relative hyperfiltration-related preservation of renal function. These observations underscore the need to control systemic metabolic disturbances in order to curb renal damage in subjects with ischemic kidney disease.
PubMed: 34540008
DOI: No ID Found -
Nutrients Jun 2021The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease...
The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease characteristics and activity. A total of 46 patients with pSS and 30 controls, without known cardiovascular disease, were enrolled in this study. A flow-mediated-dilation (FMD) of the brachial artery, plasma concentrations of the nitric oxide (NO) metabolic pathway (ADMA, L-arginine, SDMA, cGMP), and markers of endothelial inflammatory function (PAI-1, sE-selectin) and angiogenesis (angiostatin, VEGF) were analyzed. The FMD was significantly lower in pSS patients (7.56 ± 3.08 vs. 10.91 ± 1.02%, = 0.043) and positively correlated with the Ro/SS-A-antibodies ( = 0.34, = 0.03), pulmonary involvement ( = 0.52, = 0.001) and inversely with ADMA ( = -0.35, = 0.04). Plasma ADMA, L-arginine and angiostatin levels were significantly higher in pSS patients (0.39 ± 0.08 vs. 0.36 ± 0.06 µmol/L, = 0.05; 29.07 ± 6.7 vs. 25.4 ± 5.23 µmol/L, = 0.01; 152.25 ± 60.99 vs. 120.07 ± 38.7 pg/mL, = 0.0, respectively). ADMA was associated with ESSDAI ( = 0.33, = 0.02), SCORE ( = 0.57, = 0.00003) and focus score ( = 0.38, = 0.04). In the multiple regression analysis, the ESSDAI was significantly and independently associated with plasma ADMA levels ( = 0.24, = 0.04). Moreover, plasma cGMP concentrations were negatively correlated with the disease duration ( = -0.31, = 0.03). Endothelial function is impaired in patients with pSS and associated with the measures of disease activity, which supports the key-role of inflammation in developing and maintaining accelerated atherosclerosis.
Topics: Adult; Arginine; Biomarkers; Brachial Artery; Cardiovascular Diseases; Endothelium, Vascular; Female; Heart Disease Risk Factors; Humans; Inflammation; Male; Middle Aged; Regression Analysis; Sjogren's Syndrome; Vascular Diseases
PubMed: 34204342
DOI: 10.3390/nu13062072