Search Results (7)

The limited availability of primary normal human epidermal keratinocyte (NHEK) has hampered the large-scale implementation of skin models in biomedical, toxicological, and pharmaceutical research. Therefore, in this study, we aimed to establish an induced pluripotent stem cell (iPSC)-derived epidermal skin model that is not limited by donor type and cell lifespan, and evaluate whether it is equivalent to the primary NHEK-derived reconstructed epidermal skin model (RHE) for skin irritation testing. The results show that high expression of OCT4, SOX2, KLF4, c-MYC, and SSEA-4, TRA-1-60, TRA-1-81 indicated that iPSCs were successfully generated from human fibroblasts in vitro. The expression levels of ectoderm or KC marker genes CGB, IVL, KRT10, KRT14, TP63, and TBP were close to those of NHEKs. This result confirms that iPSCs were successfully differentiated into iPSC-KCs. The expression levels of iPSC-derived-RHE in FLG (60), AQP3 (151), CLDN1 (30.6), IVL (209), KRT5 (39.3), KRT10 (39.2), TSLP (99), IL-6 (53.1), IL-8 (79.4), and TNF-a (91.5) were significantly higher than those in RHE. These results indicate that iPSC-derived RHE has extremely strong vitality and renewal capacity. Meanwhile, there was no significant difference between iPSC-derived RHE and SkinEthic in predicting skin irritation, which means that our iPSC-derived RHE performed well in the test. iPSC-derived RHE can replace other skin models for skin irritation testing related to cosmetics. This technology has the potential to generate an unlimited number of genetically identical skin models and improve the reproducibility of experiments. Full article

Drought is a major environmental factor limiting crop productivity. Photosynthesis is very sensitive to drought. Basic helix-loop-helix (bHLH) transcription factors (TFs) are important in response to abiotic stress. However, their functions remain unclear. Herein, we generated CgbHLH001 (a TF gene from halophyte Chenopodium glaucum)-overexpressed (OE) and ZmbHLH-RNA interference (Ri) maize lines to investigate their photosynthesis-associated indexes under drought conditions. The photosynthetic capacity was increased in OE lines under drought stress compared with that in non-transgenic (NT) and Ri plants. A greater root biomass, higher root/shoot ratio, and a relatively lower leaf area reduction ratio was also observed in OE plants. Compared to NT and Ri plants, OE lines showed a higher chlorophyll content and net photosynthetic rate and better chlorophyll fluorescence parameters under drought conditions. Fructose and glucose contents were also significantly elevated in OE lines. Moreover, under stressful conditions, CgbHLH001 overexpression increased the expression of genes related to photosynthesis. Transcriptomic data showed that many differentially expressed genes were enriched in the photosynthetic system in OE and Ri plants under drought conditions and were prone to being upregulated under drought stress in OE plants. Therefore, our results suggest that CgbHLH001 improves photosynthetic efficiency under drought stress and confers drought tolerance in maize seedlings. Full article

Immune checkpoint inhibitor (ICI) treatment is considered as an innovative approach for cancers. Since not every patient responded well to ICI therapy, it is imperative to screen out novel signatures to predict prognosis. Based on 407 gastric cancer (GC) samples retrieved from The Cancer Genome Atlas (TCGA), 36 immune-related hub genes were identified by weighted gene co-expression network analysis (WGCNA), and eight of them (RNASE2, CGB5, INHBE, DUSP1, APOA1, CD36, PTGER3, CTLA4) were used to formulate the Cox regression model. The obtained risk score was proven to be significantly correlated with overall survival (OS), consistent with the consequence of the Gene Expression Omnibus (GEO) cohort (n = 433). Then, the relationship between the risk score and clinical, molecular and immune characteristics was further investigated. Results showed that the low-risk subgroup exhibited higher mutation rate, more M1 macrophages, CD8⁺ and CD4⁺ T cells infiltrating, more active MHC-I, and bias to “IFN-γ Dominant” immune type, which is consistent with our current understanding of tumor prognostic risk. Furthermore, it is suggested that our model can accurately predict 1-, 2-, and 3-year OS of GC patients, and that it was superior to other canonical models, such as TIDE and TIS. Thus, these eight genes are probably considered as potential signatures to predict prognosis and to distinguish patient benefit from ICI, serving as a guiding individualized immunotherapy. Full article

Abiotic stresses, such as salt and drought, significantly affect plant development and are the major limiting factors for crop quality and productivity. The manipulation of genes involved in plant stress response facilitates plant mitigation of adverse environments. In this study, we characterized CgbZIP1, a differentially expressed gene under normal and salinity conditions in Chrysanthemum grandiflora. CgbZIP1 was significantly upregulated by salt stress and also strongly responsive to drought stress and ABA treatments. Bioinformatics and subcellular localization analyses revealed that CgbZIP1 is a bZIP transcription factor and localized to the nucleus. Transgenic tobacco plants overexpressing CgbZIP1 exhibited significantly enhanced salt and drought stress tolerance associated with characteristic morphological and physiological indexes. The results demonstrate the important role CgbZIP1 plays in plant stress response and suggest its potential use in other crops for improved stress resistance. Full article

Chromogranin A (CgA), B (CgB), and C (CgC), the family members of the granin glycoproteins, are associated with diabetes. These proteins are abundantly expressed in neurons, endocrine, and neuroendocrine cells. They are also present in other areas of the body. Patients with diabetic retinopathy have higher levels of CgA, CgB, and CgC in the vitreous humor. In addition, type 1 diabetic patients have high CgA and low CgB levels in the circulating blood. Plasma CgA levels are increased in patients with hypertension, coronary heart disease, and heart failure. CgA is the precursor to several functional peptides, including catestatin, vasostatin-1, vasostatin-2, pancreastatin, chromofungin, and many others. Catestatin, vasostain-1, and vasostatin-2 suppress the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in human vascular endothelial cells. Catestatin and vasostatin-1 suppress oxidized low-density lipoprotein-induced foam cell formation in human macrophages. Catestatin and vasostatin-2, but not vasostatin-1, suppress the proliferation and these three peptides suppress the migration in human vascular smooth muscles. Chronic infusion of catestatin, vasostatin-1, or vasostatin-2 suppresses the development of atherosclerosis of the aorta in apolipoprotein E-deficient mice. Catestatin, vasostatin-1, vasostatin-2, and chromofungin protect ischemia/reperfusion-induced myocardial dysfunction in rats. Since pancreastatin inhibits insulin secretion from pancreatic β-cells, and regulates glucose metabolism in liver and adipose tissues, pancreastatin inhibitor peptide-8 (PSTi8) improves insulin resistance and glucose homeostasis. Catestatin stimulates therapeutic angiogenesis in the mouse hind limb ischemia model. Gene therapy with secretoneurin, a CgC-derived peptide, stimulates postischemic neovascularization in apolipoprotein E-deficient mice and streptozotocin-induced diabetic mice, and improves diabetic neuropathy in db/db mice. Therefore, CgA is a biomarker for atherosclerosis, diabetes, hypertension, and coronary heart disease. CgA- and CgC--derived polypeptides provide the therapeutic target for atherosclerosis and ischemia-induced tissue damages. PSTi8 is useful in the treatment of diabetes. Full article

Antimicrobial peptides (AMPS) are ancestral components in the evolution of immunity from protozoans to metazoans. Their expression can be constitutive or inducible by infectious challenge. Although characterized in detail in their structure and activity, the temporal and spatial expression of AMPS during vertebrate embryogenesis is still poorly understood. In the present study, we identified selected AMPs in zebrafish, and characterized their expression during early development, and upon experimental immune challenge in adult animals, with the goal of establishing this genetically-tractable model system for further AMP studies. By mining available genomic databases, zebrafish AMP sequences homologous to AMPs from other vertebrates were selected for further study. These included parasin I and its enzyme cathepsin D, β-defensin (DB1), liver-expressed antimicrobial peptide 2 (LEAP2), bactericidal permeability-increasing protein (BPI), and chromogranin-A and -B (CgA and CgB). Specific primers were designed for RT-PCR amplification of each AMP gene of interest and amplicons between 242 bp and 504 bp were obtained from RNA extracted from adult zebrafish. Sequencing of the amplicons and alignment of their deduced amino acid sequences with those from AMPs from other vertebrate species confirmed their identity. The temporal expression of AMPs was investigated by RT-PCR analysis in fertilized oocytes, embryos, and adult individuals. Parasin I and chatepsin D transcripts were detectable immediately after fertilization, while the transcripts for CgA and CgB became evident starting at 48 h post fertilization. Mature transcripts of LEAP2 and DB1 were detectable only in the adult zebrafish, while BPI transcripts were detectable starting from the 12th day post fertilization. To explore the possible upregulation of AMP expression by infectious challenge, experiments were carried out in adult zebrafish by intraperitoneal injection of a cocktail of lipopolysaccharide and lipoteichoic acid. Except for CgA and CgB, amplicons corresponding to all tested AMPs showed stronger signals in the experimental animals as compared to the unchallenged controls. This study provided information on the early expression of AMPs in zebrafish from ontogeny to adulthood and their inducibility by microbials. This information could be useful to actuate new prophylactic strategies as an alternative to the use of antibiotics in culture. Full article

Human chorionic gonadotropin beta subunit (CGB) is a marker of pregnancy as well as trophoblastic and nontrophoblastic tumors. CGB is encoded by a cluster of six genes, of which type II genes (CGB3/9, 5 and 8) have been shown to be upregulated in relation to type I genes (CGB6/7) in both placentas and tumors. Recent studies revealed that CGB1 and CGB2, originally considered as pseudogenes, might also be active, however, the protein products of these genes have not yet been identified. Our study demonstrates the presence of CGB1 and CGB2 transcripts in ovarian carcinomas. While CGB1 and CGB2 gene activation was not detected in normal ovaries lacking cancerous development, our study demonstrates the presence of CGB1 and CGB2 transcripts in 41% of analyzed ovarian cancer cases. Full article