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Developmental Cell Feb 2003Members of the TGFbeta superfamily play many roles in embryonic development and adult tissue homeostasis. Now recent work focused on growth and differentiation factors... (Review)
Review
Members of the TGFbeta superfamily play many roles in embryonic development and adult tissue homeostasis. Now recent work focused on growth and differentiation factors (GDFs) suggest that these TGFbeta-like molecules may also control organ size and may, in fact, be the long sought after chalones, or negative growth regulators.
Topics: Animals; Cell Differentiation; Cell Division; Growth Inhibitors; Humans; Transforming Growth Factor beta
PubMed: 12586054
DOI: 10.1016/s1534-5807(03)00027-3 -
Annals of Agricultural and... Dec 2021Human oxidative stress-induced growth inhibitor 1 (OSGIN1) is a protein identified in 2001 which belongs to the OKL38 protein family. The aim of the study was to...
INTRODUCTION AND OBJECTIVE
Human oxidative stress-induced growth inhibitor 1 (OSGIN1) is a protein identified in 2001 which belongs to the OKL38 protein family. The aim of the study was to investigate the levels of this protein depending on the severity of alcohol-induced liver cirrhosis.
MATERIAL AND METHODS
The study group consisted of 60 patients: 30 patients with cirrhosis in the P-Ch A and B stage and 30 in the P-Ch C stage. The control group consisted of 18 healthy individuals without liver diseases, who did not abuse alcohol. Oxidative stress induced growth inhibitor 1 (OSGIN1), fibroblast growth factor 1 (FGF1) and fibroblast growth factor 21 (FGF21) were determined in blood serum using enzyme-linked immunosorbent assay (ELISA) kits. All absorbance readings were conducted using an Epoch Microplate Spectrophotometer (BioTek Instrumentals, Inc., Winooski, VT, USA). OSGIN1, FGF1 and FGF21 concentrations were determined using Sandwich enzyme immunoassay kits (by Cloud Clone Corp., Katy, TX, USA). Statistica 13.3 (TIBCO Software, Inc.) was used for data analysis.
RESULTS
The concentration of OSGIN1 was 0.028 ± 0.017 in the control group which increased with the advancement of liver cirrhosis (stage of Pugh-Child): 0.075 ± 0.098 in the P-Ch A + B group and 0.121 ± 0.134 in the P-Ch C stage. Multiple comparison tests confirmed statistically significant differences in OSGIN1 concentration between the control group and P-Ch C (p <0.02). Significant correlations were noted between OSGIN1 and FGF1 (r = 0.39; p = 0.004) and between OSGIN1 and FGF21 (r = 0.53; p <0.0001).
CONCLUSIONS
The study revealed that the level of OSGIN1 increased significantly in the P-Ch C stage of liver cirrhosis. It is possible that OSGIN1 may be used for the non-invasive diagnosis of ALD, but its possible diagnostic value is still very uncertain.
Topics: Child; Fibrosis; Growth Inhibitors; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Oxidative Stress
PubMed: 34969228
DOI: 10.26444/aaem/144380 -
Molecular Therapy : the Journal of the... Feb 2023Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the interleukin-6 (IL-6) superfamily. LIF was initially discovered as a factor to induce the... (Review)
Review
Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the interleukin-6 (IL-6) superfamily. LIF was initially discovered as a factor to induce the differentiation of myeloid leukemia cells and thus inhibit their proliferation. Subsequent studies have highlighted the multi-functions of LIF under a wide variety of physiological and pathological conditions in a highly cell-, tissue-, and context-dependent manner. Emerging evidence has demonstrated that LIF plays an essential role in the stem cell niche, where it maintains the homeostasis and regeneration of multiple somatic tissues, including intestine, neuron, and muscle. Further, LIF exerts a crucial regulatory role in immunity and functions as a protective factor against many immunopathological diseases, such as infection, inflammatory bowel disease (IBD), and graft-verse-host disease (GVHD). It is worth noting that while LIF displays a tumor-suppressive function in leukemia, recent studies have highlighted the oncogenic role of LIF in many types of solid tumors, further demonstrating the complexities and context-dependent effects of LIF. In this review, we summarize the recent insights into the roles and mechanisms of LIF in stem cell homeostasis and regeneration, immunity, and cancer, and discuss the potential therapeutic options for human diseases by modulating LIF levels and functions.
Topics: Humans; Leukemia Inhibitory Factor; Growth Inhibitors; Cell Differentiation; Interleukin-6; Leukemia Inhibitory Factor Receptor alpha Subunit; Lymphokines
PubMed: 36575793
DOI: 10.1016/j.ymthe.2022.12.016 -
International Journal of Molecular... Jul 2009Vascular endothelial growth inhibitor (VEGI), also known as tumour necrosis factor superfamily member 15 (TNFSF15) and TNF ligand related molecule 1 (TL1), is a recently... (Review)
Review
Vascular endothelial growth inhibitor (VEGI), also known as tumour necrosis factor superfamily member 15 (TNFSF15) and TNF ligand related molecule 1 (TL1), is a recently identified anti-angiogenic cytokine that belongs to the TNF superfamily. Three isoforms of VEGI, VEGI 174, 192, and 251 have been documented, all sharing 151 common C-terminal amino acids but differing in their N-terminal regions. The investigations into the biological functions of VEGI have pointed to a potential cancer inhibitory role for the cytokine. The inhibitory effects of VEGI on cancer are manifested in three main areas, the direct effect on cancer cells, the anti-angiogenic effects on endothelial cells, and stimulation of maturation of dendric cells. The clinical aspect of VEGI in cancer is also being explored in recent years. The present article overviews the recent progress on this molecule and discusses the value of VEGI as a potential therapeutic target in cancer therapy.
Topics: Angiogenesis Inhibitors; Humans; Neoplasms; Neovascularization, Pathologic; Protein Isoforms; Tumor Necrosis Factor Ligand Superfamily Member 15
PubMed: 19513527
DOI: 10.3892/ijmm_00000198 -
Poultry Science Apr 2023Avian pathogenic E. coli (APEC), a causative agent of colibacillosis, is associated with high mortality and morbidity which results in severe economic losses to the...
Avian pathogenic E. coli (APEC), a causative agent of colibacillosis, is associated with high mortality and morbidity which results in severe economic losses to the poultry industry worldwide. APEC can be transmitted to humans through the consumption of contaminated poultry products. The limited effect of the current vaccines and the advent of drug-resistant strains have necessitated the development of alternative therapies. Previously, we identified 2 small molecules (SMs; [quorum sensing inhibitor; QSI-5] and [growth inhibitor; GI-7]) with high efficacy in vitro and in chickens subcutaneously challenged with APEC O78. Here, we optimized the oral challenge dose of APEC O78 in chickens to mimic the infection in the natural settings, evaluated the efficacy of the GI-7, QSI-5, and combination of GI-7 and QSI-5 (GI7+ QSI-5) in chickens orally infected with APEC, and compared their efficacy to sulfadimethoxine (SDM), an antibiotic currently used to treat APEC. Using the optimized dose of each SM in drinking water, GI-7, QSI-5, GI7+ QSI-5, and SDM were evaluated in chickens challenged with the optimized dose of APEC O78 (1 × 10 CFU/chicken; orally; d 2 of age) and grown on built-up floor litter. Reduction in mortality was 90, 80, 80, and 70% in QSI-5, GI-7+QSI-5, GI-7, and SDM treated groups compared to the positive control (PC), respectively. GI-7, QSI-5, GI-7+QSI-5, and SDM reduced the APEC load in the cecum by 2.2, 2.3, 1.6, and 0.6 logs and in the internal organs by 1.3, 1.2, 1.4, and 0.4 logs compared to PC (P < 0.05), respectively. The cumulative pathological lesions scores were 0.51, 0.24, 0.0, 0.53, and 1.53 in GI-7, QSI-5, GI-7+QSI-5, SDM, and PC groups, respectively. Overall, GI-7 and QSI-5 individually have promising effects as a potential antibiotic-independent approach to control APEC infections in chickens.
Topics: Humans; Animals; Escherichia coli; Chickens; Quorum Sensing; Growth Inhibitors; Escherichia coli Infections; Anti-Bacterial Agents; Sulfadimethoxine; Poultry Diseases
PubMed: 36863122
DOI: 10.1016/j.psj.2023.102543 -
International Journal of Molecular... Jul 2022Aedes aegypti is the main vector that transmits viral diseases such as dengue, hemorrhagic dengue, urban yellow fever, zika, and chikungunya. Worldwide, many cases of...
Aedes aegypti is the main vector that transmits viral diseases such as dengue, hemorrhagic dengue, urban yellow fever, zika, and chikungunya. Worldwide, many cases of dengue have been reported in recent years, showing significant growth. The best way to manage diseases transmitted by Aedes aegypti is to control the vector with insecticides, which have already been shown to be toxic to humans; moreover, insects have developed resistance. Thus, the development of new insecticides is considered an emergency. One way to achieve this goal is to apply computational methods based on ligands and target information. In this study, sixteen compounds with acceptable insecticidal activities, with 100% larvicidal activity at low concentrations (2.0 to 0.001 mg·L−1), were selected from the literature. These compounds were used to build up and validate pharmacophore models. Pharmacophore model 6 (AUC = 0.78; BEDROC = 0.6) was used to filter 4793 compounds from the subset of lead-like compounds from the ZINC database; 4142 compounds (dG < 0 kcal/mol) were then aligned to the active site of the juvenile hormone receptor Aedes aegypti (PDB: 5V13), 2240 compounds (LE < −0.40 kcal/mol) were prioritized for molecular docking from the construction of a chitin deacetylase model of Aedes aegypti by the homology modeling of the Bombyx mori species (PDB: 5ZNT), which aligned 1959 compounds (dG < 0 kcal/mol), and 20 compounds (LE < −0.4 kcal/mol) were predicted for pharmacokinetic and toxicological prediction in silico (Preadmet, SwissADMET, and eMolTox programs). Finally, the theoretical routes of compounds M01, M02, M03, M04, and M05 were proposed. Compounds M01−M05 were selected, showing significant differences in pharmacokinetic and toxicological parameters in relation to positive controls and interaction with catalytic residues among key protein sites reported in the literature. For this reason, the molecules investigated here are dual inhibitors of the enzymes chitin synthase and juvenile hormonal protein from insects and humans, characterizing them as potential insecticides against the Aedes aegypti mosquito.
Topics: Aedes; Animals; Computational Biology; Dengue; Growth Inhibitors; Humans; Insecta; Insecticides; Larva; Molecular Docking Simulation; Mosquito Vectors; Zika Virus; Zika Virus Infection
PubMed: 35897792
DOI: 10.3390/ijms23158218 -
BMC Microbiology Mar 2021Lignocellulosic material is a suitable renewable carbon and energy source for microbial cell factories, such as Yarrowia lipolytica. To be accessible for microorganisms,...
BACKGROUND
Lignocellulosic material is a suitable renewable carbon and energy source for microbial cell factories, such as Yarrowia lipolytica. To be accessible for microorganisms, the constituent sugars need to be released in a hydrolysis step, which as a side effect leads to the formation of various inhibitory compounds. However, the effects of these inhibitory compounds on the growth of Y. lipolytica have not been thoroughly investigated.
RESULTS
Here we show the individual and combined effect of six inhibitors from three major inhibitor groups on the growth of Y. lipolytica. We engineered a xylose consuming strain by overexpressing the three native genes XR, XDH, and XK and found that the inhibitor tolerance of Y. lipolytica is similar in glucose and in xylose. Aromatic compounds could be tolerated at high concentrations, while furfural linearly increased the lag phase of the cultivation, and hydroxymethylfurfural only inhibited growth partially. The furfural induced increase in lag phase can be overcome by an increased volume of inoculum. Formic acid only affected growth at concentrations above 25 mM. In a synthetic hydrolysate, formic acid, furfural, and coniferyl aldehyde were identified as the major growth inhibitors.
CONCLUSION
We showed the individual and combined effect of inhibitors found in hydrolysate on the growth of Y. lipolytica. Our study improves understanding of the growth limiting inhibitors found in hydrolysate and enables a more targeted engineering approach to increase the inhibitor tolerance of Y. lipolytica. This will help to improve the usage of Y. lipolytica as a sustainable microbial cell factory.
Topics: Acrolein; Formates; Furaldehyde; Growth Inhibitors; Hydrolysis; Industrial Microbiology; Lignin; Yarrowia
PubMed: 33685391
DOI: 10.1186/s12866-021-02126-0 -
Contrast Media & Molecular Imaging 2022The purpose of this study was to investigate the effect of vitamin C combined with growth inhibitors on serum miR-130a, nitric oxide (NO), and hemostasis in the...
The purpose of this study was to investigate the effect of vitamin C combined with growth inhibitors on serum miR-130a, nitric oxide (NO), and hemostasis in the treatment of upper gastrointestinal bleeding (UGIB) in cirrhosis. Eighty patients with cirrhosis UGIB treated in our hospital from March 2021 to March 2022 were selected and divided into two groups using the random number table method. The control group received growth inhibitor treatment, while the observation group was given vitamin C combined with growth inhibitor treatment for 3 d. The hemostatic effect, serum laboratory indexes (miR-130a, NO), liver function indexes (aspartate aminotransferase (AST), alanine aminotransferase (ALT)), adverse effects, and 24 h hemostasis rate were compared between the two groups. The hemostasis time in the observation group was shorter than that in the control group, and the blood transfusion volume was lower than that in the control group. There was no statistical difference regarding the portal blood flow, miR-130a, NO, AST, and ALT indexes between the two groups before treatment. After treatment, the portal blood flow, miR-130a, NO, AST, and ALT indexes in both groups were lower than those before treatment, and all of them were lower in the observation group than in the control group. Adverse reactions showed no significant difference between the two groups of patients with cirrhosis UGIB,, while the 24 h hemostasis rate in the observation group (97.50%) was significantly higher than that in the control group (77.50%). Vitamin C combined with growth inhibitor was effective in the treatment of cirrhotic UGIB, which could effectively shorten the hemostasis time, reduce the transfusion volume and portal blood flow, and improve miR-130a, NO, and liver function levels of patients, with higher safety, and is worthy of clinical promotion.
Topics: Ascorbic Acid; Gastrointestinal Hemorrhage; Growth Inhibitors; Humans; Liver Cirrhosis; MicroRNAs
PubMed: 35935307
DOI: 10.1155/2022/5319786 -
The Yale Journal of Biology and Medicine 1992This article describes studies with four peptides, epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), gastrin-releasing peptide/bombesin (GRP),... (Review)
Review
This article describes studies with four peptides, epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), gastrin-releasing peptide/bombesin (GRP), and gastrin. The mitogenic and anti-secretory activities of EGF/TGF alpha appear to be mediated by a single class of high-affinity membrane receptors but may involve different signal transducing mechanisms. Biological activity of EGF resides in the N-terminal 42 amino acid fragment with the C-terminal undecapeptide determining binding affinity. A parenteral depot formulation of an EGF-related peptide or a small molecule agonist of the EGF receptor could have utility in treating various ulcerative disorders of the gut. Although antagonism of EGF (and thus TGF alpha) receptors and/or transducing mechanisms is frequently cited as a potential therapeutic approach to hyperproliferative diseases, blocking the action of TGF alpha, GRP, or gastrin with neutralizing antibodies or receptor antagonists did not influence the growth of a wide range of solid tumors in nude mice. These findings suggest that, unless tumor growth displays absolute dependency on one particular mitogen, antagonism of a specific growth factor is unlikely to have great effect in cancer therapy.
Topics: Amino Acid Sequence; Animals; Epidermal Growth Factor; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Growth Inhibitors; Growth Substances; Humans; Molecular Sequence Data; Protein Structure, Secondary
PubMed: 1341074
DOI: No ID Found -
Behavioural Brain Research Mar 2022Running wheel exercise training (RWE) and skilled reaching training (SRT) are physical training approaches with positive effects on cognitive function. However, few...
Running wheel exercise training (RWE) and skilled reaching training (SRT) are physical training approaches with positive effects on cognitive function. However, few studies have compared the different effects of these exercises on long-term memory, and their mechanism remains unknown. This study investigated the effects of SRT and RWE, at the recovery stage, on the cognitive function of transient middle cerebral artery occlusion (tMCAO) rats and explored their association with NgR1/Rho-A/ROCK/LOTUS/LGI1 signaling. Adult Sprague-Dawley rats (n = 55) were divided into four groups after pretraining: SRT, RWE, tMCAO, and Sham. Rats were subjected to modified neurological severity score (mNSS) measurements and forelimb grip strength and the Morris water maze tests. Using immunofluorescence and western blotting, we evaluated axonal growth inhibitor expression in the peri-infarct cortex on days 28 and 56 after tMCAO. Results showed the mNSS reduced, whereas the grip strengths improved in RWE and SRT groups. The escape latency in the Morris water maze test was shorter, whereas the number of times of crossing the platform was higher in both the SRT and RWE groups than in the tMCAO group on day 56; furthermore, the parameters in the SRT group improved compared to those in the RWE group. Physical exercise training could improve cognitive functions by reducing the expression of the NgR1/RhoA/ROCK axon growth inhibitors and increasing the expression of the endogenous antagonists LOTUS/LGI1. Exercise training beginning at the recovery stage could improve the cognitive function in tMCAO rats through a mechanism probably associated with the axonal growth inhibitor pathway.
Topics: Animals; Axons; Behavior, Animal; Cerebral Cortex; Cognitive Dysfunction; Disease Models, Animal; Exercise Therapy; Growth Inhibitors; Ischemic Stroke; Male; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Signal Transduction; Stroke Rehabilitation
PubMed: 34971645
DOI: 10.1016/j.bbr.2021.113730