- Biofunctionalized self-assembly of peptide amphiphile induces the differentiation of bone marrow mesenchymal stem cells into neural cells. [Journal Article]
- MCMol Cell Biochem 2018 Jun 21
- Bone marrow mesenchymal stem cells (BMSCs) are multipotential differentiation cells which can differentiate into different cell types such as osteoblasts, chondrocytes, adipocytes, cardiomyocytes, he...
Bone marrow mesenchymal stem cells (BMSCs) are multipotential differentiation cells which can differentiate into different cell types such as osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial cells, and neuronal cells. Such multipotential differentiation makes them attractive for stem cell-based therapy aimed at treating previously incurable disorders. In the present work, we encapsulated BMSCs into a hydrogel with a three-dimensional (3D) network of nanofibers, formed from self-assembling of peptide amphiphile. The self-assembling of peptide amphiphile into hydrogel was triggered by mixing cell suspensions with dilute aqueous solutions of amphipathic peptide. Moreover, this hydrogel was designed to present cells the neurite-promoting laminin epitope IKVAV at nearly van der Waals density, which induced the successful differentiation of BMSCs into neural cells.
- Loss of the basic helix-loop-helix transcription factor Bhlhe41 induces cell death and impairs neurite outgrowth in Neuro2a cells. [Journal Article]
- MCMol Cell Biochem 2018 Jun 20
- The basic helix-loop-helix (bHLH) superfamily of transcription factors have been implicated in a wide range of cellular functions such as proliferation, differentiation, tumorigenesis, and circadian ...
The basic helix-loop-helix (bHLH) superfamily of transcription factors have been implicated in a wide range of cellular functions such as proliferation, differentiation, tumorigenesis, and circadian rhythms. In a previous siRNA-based screen, bHLH family member e41 (BHLHE41) had been identified as a putative regulator of neuronal differentiation; however, its function remains largely elusive. To this end, using the CRISPR-Cas9 system, we established an isogenic Neuro2a (N2a) cell line with biallelic targeting of Bhlhe41 gene (Bhlhe41-/-). In undifferentiated N2a cells, complete knockout of Bhlhe41 resulted in marked proliferation inhibition, together with accumulation of apoptotic cells. Furthermore, retinoic acid (RA)-induced neurite outgrowth and expression of neuronal markers are significantly weakened in Bhlhe41-/- cells. We also showed that the activity of ERK1/2 signaling, a key regulator of neuronal differentiation, is likewise impaired in knockout cells. Together, these results suggest that Bhlhe41 plays critical roles in regulating cell death and neurite outgrowth in N2a cells.
- Cellular miR-2909 RNomics governs the genes that ensure immune checkpoint regulation. [Journal Article]
- MCMol Cell Biochem 2018 Jun 20
- Cross-talk between coding RNAs and regulatory non-coding microRNAs, within human genome, has provided compelling evidence for the existence of flexible checkpoint control of T-Cell activation. The pr...
Cross-talk between coding RNAs and regulatory non-coding microRNAs, within human genome, has provided compelling evidence for the existence of flexible checkpoint control of T-Cell activation. The present study attempts to demonstrate that the interplay between miR-2909 and its effector KLF4 gene has the inherent capacity to regulate genes coding for CTLA4, CD28, CD40, CD134, PDL1, CD80, CD86, IL-6 and IL-10 within normal human peripheral blood mononuclear cells (PBMCs). Based upon these findings, we propose a pathway that links miR-2909 RNomics with the genes coding for immune checkpoint regulators required for the maintenance of immune homeostasis.
- Comparative effects of calcium and potassium channel modulators on ischemia/reperfusion injury in the isolated rat heart. [Journal Article]
- MCMol Cell Biochem 2018 Jun 19
- The aim of this study was to examine and compare the effects of the acute administration of verapamil or amlodipine as representatives of the calcium channel blockers or nicorandil as a representativ...
The aim of this study was to examine and compare the effects of the acute administration of verapamil or amlodipine as representatives of the calcium channel blockers or nicorandil as a representative of the mitochondrial ATP-dependent potassium (KATP) channel opener to cardiac contractility, coronary flow, and oxidative stress markers on ischemia/reperfusion injury in the isolated rat heart. The hearts of adult male Wistar albino rats (n = 60 total, 12 per group) were divided into five groups, two controls (preconditioning with Krebs-Henseleit solution) and three experimental depending on acute administrated pharmacological agents (0,63 µmol/L of verapamil, 0,1 µmol/L of amlodipine, and 200 µmol/L of nicorandil). After stabilization and 5 min of preconditioning in experimental groups, hearts from I/R control and all experimental groups underwent global ischemia (20 min) and reperfusion (30 min). Hearts from sham group were continuously followed for 50 min, after stabilization period. Cardiodynamic parameters and coronary flow were recorded at the end of stabilization (S), at the last minute of pharmacological preconditioning (P) and at intervals of 5 min after global ischemia, during reperfusion, or in case of sham group during 20-50 min after stabilization. At the same intervals, we collected coronary venous effluent from which we spectrophotometrically measured the parameters of oxidative stress: the index of lipid peroxidation, superoxide anion radical, hydrogen peroxide, and nitrite. In summary, our findings clearly indicate that the blocking of the calcium channel or the activation of KATP may mediate the protective effect of myocardial preconditioning. The ex vivo results showed that all examined drugs after ischemia and reperfusion have beneficial cardioprotective properties associated with lower values of major pro-oxidative molecules. Obtained effects seem to be the most convincible in case of nicorandil.
- Hsa-miR-370 inhibited P-selectin-induced cell adhesion in human colon adenocarcinoma cells. [Journal Article]
- MCMol Cell Biochem 2018 Jun 19
- Sialyl Lewis x (sLex) is a minimal recognition motif for ligands of P-selectin and plays an important role in tumor cell adhesion and migration. Thus, targeting sLex could be an effective method to p...
Sialyl Lewis x (sLex) is a minimal recognition motif for ligands of P-selectin and plays an important role in tumor cell adhesion and migration. Thus, targeting sLex could be an effective method to prevent tumor metastasis. In this study, we aimed to identify a microRNA (miRNA) which is capable to suppress the expression of sLex. MicroRNAs which may target ST3GAL4 were predicted by the online tools. Colo 320 HSR human colon adenocarcinoma cells were employed. The transcriptional and translational levels of ST3GAL4 were evaluated by western blotting and Real-time quantitative polymerase chain reaction. Cell adhesion and spread were assessed with or without hsa-miR-370 treatment. It was shown that hsa-miR-370 inhibited the expression of sLex in colo-320 cells, which repressed the binding of P-selectin, and led to reduced cell attachment and spread. Our results found that P-selectin-induced elevations of p-p38 and p-PI3K levels were significantly inhibited by hsa-miR-370, indicating that repressed sLex level is able to reduce the P-selectin binding and therefore eliminating the P-selectin-induced activation of p38 and PI3K signaling. In conclusion, we found that hsa-miR-370 specifically inhibits the expression of sLex, represses cell adhesion and spreading in colo-320 cells. Our study provides a possible effective treatment against tumor invasion.
- Correlation between S100A11 and the TGF-β1/SMAD4 pathway and its effects on the proliferation and apoptosis of pancreatic cancer cell line PANC-1. [Journal Article]
- MCMol Cell Biochem 2018 Jun 19
- S100A11 as a S100 protein family member has been documented to play dual-direction regulation over cancer cell proliferation. We explored the role of S100A11 in the proliferation and apoptosis of pan...
S100A11 as a S100 protein family member has been documented to play dual-direction regulation over cancer cell proliferation. We explored the role of S100A11 in the proliferation and apoptosis of pancreatic cancer cell line PANC-1 and the potential mechanisms involving the TGF-β1/SMAD4/p21 pathway. S100A11 and TGF-β1 protein expressions in 30 paraffin-embedded specimens were evaluated by immunohistochemistry. S100A11 and TGF-β1 expression in PANC-1 cell line was suppressed using small interfering RNA (siRNA), respectively. Subsequently, pancreatic cancer cell apoptosis was measured by Cell Counting Kit-8 and flow cytometry, and S100A11 and TGF-β1/SMAD4/p21 pathway proteins and genes were detected with Western blotting and quantitative polymerase chain reaction (qPCR). S100A11 cytoplasmic/nuclear protein translocation was examined using NE-PER® cytoplasm/nuclear protein extraction in cells interfered with TGF-β1 siRNA. Our results showed that S100A11 expression was positively correlated with TGF-β1 expression in pancreatic cancerous tissue. Silencing TGF-β1 down-regulated intracellular P21WAF1 expression by 90%, blocked S100A11 from cytoplasm entering nucleus, and enhanced cell proliferation. Silencing S100A11 down-regulated intracellular P21 expression and promoted cell apoptosis without significantly changing TGF-β1 and SMAD4 expression. Our findings revealed that S100A11 and TGF-β1/SMAD4 signaling pathway were related but mutually independent in regulating PANC-1 cells proliferation and apoptosis. Other independent mechanisms might be involved in S100A11's regulation of pancreatic cell growth. S100A11 could be a potential gene therapy target for pancreatic cancer.
- Silibinin-induced autophagy mediated by PPARα-sirt1-AMPK pathway participated in the regulation of type I collagen-enhanced migration in murine 3T3-L1 preadipocytes. [Journal Article]
- MCMol Cell Biochem 2018 Jun 18
- Preadipocyte migration is a fundamental and important process for the development of tissue organization, especially in the development of primitive adipose tissue and adipocyte tissue wound healing....
Preadipocyte migration is a fundamental and important process for the development of tissue organization, especially in the development of primitive adipose tissue and adipocyte tissue wound healing. However, excessive migration may result in abnormal development and fibrosis-related diseases such as hypertrophic scar. We previously reported that type I collagen (collagen I) enhanced migration of 3T3-L1 preadipocytes via phosphorylation and/or acetylation of NF-κB p65, and the enhanced cell migration is repressed by silibinin treatment through sirt1. It is known that sirt1 has an ability to deacetylate acetylated NF-κB p65, but little is known about the effect of sirt1 on phosphorylated NF-κB p65. This study aims to examine the potential effect of sirt1 on the regulation of phosphorylated NF-κB p65 and the underlying mechanism. Autophagy is involved in many physiological and pathological processes, including regulation of cell migration as well as in cellular homeostasis. The present study demonstrates that silibinin induces autophagy in a dose-dependent manner in 3T3-L1 cells. Autophagy is under the regulation of sirt1/AMPK pathway, and inhibits collagen I-enhanced migration of 3T3-L1 cells through negative regulation of NF-κB p65 phosphorylation but not acetylation. The expression of peroxisome proliferator-activated receptor α (PPARα) is up-regulated with silibinin accompanying up-regulation of autophagy through activating sirt1 in 3T3-L1 cells. Taken together, these findings indicate that silibinin-induced autophagy is mediated by up-regulation of PPARα-sirt1-AMPK, contributing to repression of type I collagen-enhanced migration in murine 3T3-L1 preadipocytes through down-regulation of phosphorylated NF-κB p65.
- The possible antidiabetic effects of vitamin D receptors agonist in rat model of type 2 diabetes. [Journal Article]
- MCMol Cell Biochem 2018 Jun 16
- Vitamin D3 deficiency was found to be tightly linked to many health problems including metabolic syndrome, cancer, cardiovascular diseases, and type 2 diabetes mellitus. In our study, we tested the p...
Vitamin D3 deficiency was found to be tightly linked to many health problems including metabolic syndrome, cancer, cardiovascular diseases, and type 2 diabetes mellitus. In our study, we tested the possible antidiabetic effects of one of vitamin D3 analogs, alfacalcidol, solely or in a combination with metformin on type 2 diabetic rats. Type 2 diabetic model rats were induced by feeding high-fat diet for 4 weeks followed by intraperitoneal injection of streptozotocin. In addition to the control group, the diabetic rats were divided into four groups: untreated, metformin-treated, alfacalcidol-treated, and combination-treated group (metformin + alfacalcidol) for 4 weeks. The level of fasting blood glucose, fasting serum insulin, homeostatic model of insulin resistance, serum lipid profile, liver enzymes, calcium, phosphorus, and 25-hydroxyvitamin D3 were also determined. Besides, sterol regulatory element binding protein-1c (SREBP-1c) and vitamin D receptors (VDR) gene expression at mRNA and protein levels were evaluated. The level of significance was fixed at P ≤ 0.05 for all statistical tests. Alfacalcidol, solely or combined with metformin, significantly ameliorated glucose homeostasis and lipid profile parameters (P < 0.001) with a neutral effect on calcium and phosphorus levels. Significant downregulation of mRNA expression of SREBP-1c in the liver, white as well as brown adipose tissues (P < 0.001) and different patterns of mRNA expression of VDR gene in pancreas and white adipose tissue were observed in rats treated with alfacalcidol solely or in combination with metformin. Vitamin D3 analogs can modulate glucose parameters and lipid metabolism in a diabetic rat model and it provides additional protective effects when combined with metformin.
- Knockdown of SUMO1P3 represses tumor growth and invasion and enhances radiosensitivity in hepatocellular carcinoma. [Journal Article]
- MCMol Cell Biochem 2018 Jun 15
- Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with high recurrence and metastasis rates. Radiotherapy represents a major therapeutic option for HCC patients. Howe...
Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with high recurrence and metastasis rates. Radiotherapy represents a major therapeutic option for HCC patients. However, the efficacy of radiotherapy has been limited due to the development of intrinsic radioresistance of the tumor cells. Small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3), one member of SUMO pseudogene family, is a novel identified lncRNA that was originally identified to be upregulated in gastric cancer. However, the detailed roles of SUMO1P3 in HCC development remain to be elucidated. Here, the expression of SUMO1P3 in HCC tissues and cells was examined by qRT-PCR. Cell proliferation, colony formation ability, invasion ability, apoptosis, and radiosensitivity were detected by MTT assay, colony formation assay, cell invasion assay, flow cytometry analysis, and survival fraction assay, respectively. We found that SUMO1P3 was significantly upregulated in HCC tissues and cells. Besides, SUMO1P3 was highly expressed in HCC patients with higher TNM stage. Furthermore, SUMO1P3 knockdown markedly suppressed cell proliferation, colony formation ability, and cell invasiveness, promoted apoptosis, and enhanced radiosensitivity of HCC cells. We concluded that the knockdown of SUMO1P3 repressed tumor growth, invasion, promoted apoptosis, and enhanced radiosensitivity in HCC, providing evidence that SUMO1P3 might be a potential novel biomarker and a therapeutic target for HCC.
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- Thioredoxin-interacting protein mediates mitochondrion-dependent apoptosis in early brain injury after subarachnoid hemorrhage. [Journal Article]
- MCMol Cell Biochem 2018 Jun 15
- Early brain injury (EBI) was reported to be the primary cause of high mortality and poor outcomes in subarachnoid hemorrhage (SAH) patients, and apoptosis is regarded as the most important physiopath...
Early brain injury (EBI) was reported to be the primary cause of high mortality and poor outcomes in subarachnoid hemorrhage (SAH) patients, and apoptosis is regarded as the most important physiopathologic mechanism during EBI. Recently, our team found that thioredoxin-interacting protein (TXNIP) links endoplasmic reticulum stress (ER stress) to neuronal apoptosis and aggravates EBI. However, the other underlying mechanisms remain unknown. Mitochondria are considered to be the central points in integrating apoptotic cell death. However, whether crosstalk between TXNIP and the mitochondria-mediated intrinsic apoptotic pathway is effective on EBI has not been previously reported. Therefore, we created an endovascular perforation SAH model in Sprague-Dawley rats to determine the possible mechanism. We found that TXNIP expression in apoptotic neurons significantly increased in the SAH group compared with the sham group. In addition, increased TXNIP expression was accompanied by remarkable changes in mitochondrial-related antiapoptotic and proapoptotic factors. Furthermore, resveratrol (RES, a TXNIP inhibitor) administration significantly downregulated the expression of TXNIP and mitochondria-related proapoptotic factors. Additionally, it attenuated SAH prognostic indicators, such as brain edema, blood-brain barrier permeability, and neurological deficits. Therefore, our study further confirms that TXNIP may participate in neuronal apoptosis through the mitochondrial signaling pathway and that TXNIP may be a target for SAH treatment.