Role of transcription factor Yin Yang 1 in hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) often has an insidious onset, and most patients are in the advanced stage and have lost the best opportunity for treatment at the time of diagnosis, resulting in a poor prognosis. As a multifunctional transcription factor, Yin Yang 1 (YY1) regulates the transcription of a variety of important genes and plays a key role in various tumors. Previous studies have shown that YY1 affects many biological behaviors such as proliferation, apoptosis, migration, and angiogenesis and is closely associated with drug resistance and poor prognosis of HCC. This article reviews the research advances in the role of YY1 in the development and progression of HCC, so as to provide a theoretical basis for the treatment of HCC.

Role of ZHX2 in regulating dorsal root ganglion μ-opioid receptor expression in mice with peripheral nerve injuryinduced pain hypersensitivity / 南方医科大学学报

OBJECTIVE@#To investigate the role of zinc-fingers and homeoboxes 2 (ZHX2) in regulating μ-opioid receptor expression in the dorsal root ganglion (DRG) in mice with peripheral nerve injury-induced pain hypersensitivity.@*METHODS@#Forty-eight male adult C57BL6J mice were randomized into 4 groups and subjected to chronic constriction injury (CCI) of the sciatic nerve or sham operation followed by microinjection of a specific small interfering RNA (siRNA) of ZHX2 or a negative control siRNA sequence (siNC) into the DRG. Seven days later, the mice were examined for changes in the hind paw withdrawal frequency (PWF), after which the DRG tissue was collected for detecting the expressions of μ-opioid receptor at the mRNA and protein levels using RT-qPCR and Western blotting. In another experiment, the DRG tissues were collected from 6 mice (21-day-old) for primary culture of the DRG neurons, which were transfected with ZHX2 siRNA or the siNC to observe the changes in the expressions of ZHX2 and μ-pioid receptor.@*RESULTS@#Microinjection of ZHX2 siRNA into the ipsilateral L3 and L4 DRGs significantly reversed CCI-induced μ-pioid receptor downregulation in the injured DRG and alleviated CCI-induced mechanical allodynia in the mice. In the cell experiment, ZHX2 knockdown obviously upregulated the mRNA and protein expressions of opioid receptor in the primary cultured DRG neurons.@*CONCLUSIONS@#ZHX2 knockdown in the DRG reverses CCI-induced down-regulation of μ opioid receptor to alleviate periphery nerve injury-induced pain hypersensitivity in mice.

HDR syndrome in a Colombian woman with a genital tract malformation: first case report in Latin America / Síndrome HDR en una mujer colombiana con una malformación genitourinaria: primer reporte de caso en Latinoamérica

ABSTRACT Objectives Hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, also known as Barakat syndrome, is an autosomal dominant transmission hereditary disease with a wide range of penetrance and expressivity. Haploinsufficiency of the GATA3 two finger zinc transcription factor is believed to be its cause. This is the first time this orphan disease is reported in Latin America, so the publishing of this report is expected to raise awareness on these types of syndrome, that are usually underdiagnosed in our region, which in turn causes an increase in the years lost to disability (YLDs) rates, as well as higher costs to be assumed by public health systems. Methods A 36-year-old Colombian woman diagnosed with parathyroid gland agenesis was referred from the Endocrinology Service to the Outpatient Service. According to her medical record, in the past she had developed hypocalcaemia, left renal agenesis, hypoparathyroidism, bicornate uterus and sensorineural hearing loss. Through a genetic analysis a pathological mutation on the short arm of the GATA 3 gen (c.404dupC, p Ala136 GlyfsTER 167) was confirmed, which led to a HDR syndrome diagnosis. Discussion This case proves that there is a possibility that mutations described in other continents may be developed by individuals from our region. Regardless of ethnicity, Barakat syndrome should be considered as a possible diagnosis in patients presenting the typical triad that has been described for this condition, since there could be underdiagnosis of this disease in Latin-America due to the lack of knowledge on this condition in said region, and that genetic counseling in these patients is of great importance for the implications of the syndrome in future generations.(AU)

RESUMEN Objetivos El síndrome de hipoparatiroidismo, sordera neurosensorial y displasia renal (HDR) también llamado síndrome de Barakat, es una enfermedad hereditaria de transmisión autosómica dominante con amplia penetrancia y expresividad genética. El síndrome es causado por la haploinsuficiencia del factor de transcripción de dedos de Zinc GATA3. Esta es la primera vez que esta enfermedad huérfana es reportada en latinoamerica, y buscamos generar consciencia de la presencia de estas enfermedades, las cuales usualmente son infradiagnósticadas en nuestro medio y llevan a un aumento de años perdidos por discapacidad y costos para el sistema de salud pública. Métodos Una mujer colombiana de 36 años ingresó a consulta externa de genética referida por el servicio de endocrinología por una agenesia de paratiroides. La paciente tenía antecedentes de hipocalcemia, agenesia renal izquierda, hipoparatiroidismo, sordera neurosensorial y útero bicorneo. Se realizó un análisis genético que confirmo una mutación patológica en el brazo corto del gen GATA3 (c.404dupC, p Ala136 GlyfsTER 167) diagnóstica del síndrome de Barakat. Discusión Este caso demuestra la posibilidad de existencia de mutaciones descritas en otros continentes en nuestra población. Sin importar la etnia, el síndrome de Barakat debe ser estudiado en pacientes que presenten la triada típica, ya que podría existir un infra diagnóstico de la enfermedad secundario al desconocimiento de la misma en Latinoamérica y teniendo en cuenta la importancia que tiene la consejería genética en estos pacientes por las implicaciones de la enfermedad en futuras generaciones.(AU)

The effects of RIPK3 overexpression on the transcription of ZFP36 gene in SH-SY5Y cells / 天津医药

Objective To investigate the signaling pathway and the key signal molecules of protein kinase (RIPK)3 in SH-SY5Y cells. Methods SH-SY5Y cells were transfected with RIPK3 expression plasmid vector to upregulate intracellular RIPK3, while the SH-SY5Y cells were transfected with empty vector plasmid, which was considered as control group. Western blot assay was used to check the expression of exogenous RIPK3 in cells. The proliferation rate of SH-SY5Y cells was determined by MTT assay at designated time to detect exogenous RIPK3 activity. Whole transcriptome sequencing (RNAseq) was used to detect the transcription of genes. Whole-transcriptomic gene transcription was measured by following Ingenuity Pathway Analysis (IPA) to obtain downstream signaling pathways and the key molecule, which were partly confirmed by following droplet digital PCR (ddPCR). Results Exogenous RIPK3 showed biological activity in SH-SY5Y, which inhibited the proliferation of cells. IPA showed that znic finger protein 36 (ZFP36) was significantly up-regulated as compared with that of the control group. The tran?scription levels of ZFP36 downstream genes such as tumor necrosis factor (TNF), brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and mRNA-decapping enzyme 2 (DCP2) were affected at the same time. Conclusion Within the limitations of this study, it seems that RIPK3 is notable for the development, inflammation and tumorigenesis of the nervous system as an independent regulator of ZFP36 gene and downstream effectors.

Clinical application of zinc finger protein A20 / 肿瘤研究与临床

Pathologist Dixit in American Michigan University found a gene induced by cytokine from human umbilical vein endothelial cells in 1990.This gene is increased in a variety of cells rapidly and coded a special kind of the zinc finger protein when being stimulated by interleukin-1 (IL-1),PLS and tumor necrosis factor (TNF).The gene was named as zinc finger protein A20 gene,and its coding protein was named as zinc finger protein A20.A20 is a kind of endogenous regulatory protein,inhibiting the inflammatory reaction and cell apoptosis through the inhibition of NF-kappa B activity.This article mainly reviewed the structure,function and clinical significance of A20.

Effects of ZHX3 gene silence on the expression of osteoblast-related factors in BMSCs / 天津医药

Objective To investigate the effects of zinc fingers and homeoboxes 3 (ZHX3) silence on expressions of smad3, smad4 and RUNX2 in bone marrow mesenchymal stem cells (BMSCs). Methods ZHX3 low expression vector (ZHX3 silent group) was constructed and was transfected to rat BMSCs. Empty vector was transfected into BMSCs and was used as vehicle control group, and wild type BMSCs was used as the control group. The cell transfection rate was measured under a fluorescence microscope, and then the successful transfection was identified. The immunocytochemistry and immu?noblotting methods were used to detect the expression levels of smad3, smad4 and RUNX2. Results (1) Cells with BMSCs phenotype can be obtained by recovery culturing. (2) After transfection, the green fluorescent protein was found in ZHX3 si?lence group and vehicle control group. Blank control group showed no significant fluorescence. The expression level of ZHX 3 was significantly lower in ZHX3 silence group than that of vehicle control group. (3) Results of immunofluorescence asssay showed that the positive expressions of smad3 and smad4 were located in nucleus and cytoplasm, the positive expression of RUNX2 was mainly located in nucleus. Positive cells were observed in three groups. There was no significant difference in fluorescence intensity between the control group and the vehicle control group, but the fluorescence intensity was significant?ly lower in ZHX3 gene silence group than that of two control groups. (4) There were no significant differences in expressions of smad3, smad4 and RUNX2 betweem control group and the vehicle control group, but they were significantly higher than those of ZHX3 silence group(P < 0.05). Conclusion ZHX3 gene silence can delay vitro osteogenesis of BMSCs, which may play a role by the down-regulated expression levels of smad3, smad4 and RUNX2.

The effect of zinc finger protein 185 on the proliferation of human glioma cells / 天津医药

Objective To explore the role of zinc finger protein (ZNF)185 in the proliferation of human glioma cells. Methods Human glioma tissues and tumor adjacent tissues were obtained from glioma patients diagnosed pathologically in Tangshan Gongren Hospital from January 2011 to December 2013. Total protein was extracted from different tissues. The ZNF185 expression was detected by Western-blot assay. Total RNA was extracted from tumor adjacent tissues. ZNF 185 cod?ing sequence was obtained by RT-PCR and inserted into pEGFPC2 plasmid to construct the ZNF185 expression vector. Li?pofactamine2000 was used to transfect the ZNF185 expression vector to human glioma cell SF767. pEGFPC2 blank vector transfected SF767 cells were used as control. Changes of cell cycle were analyzed by flow cytometry, and cell proliferation was analyzed by MTT assay. Results The expression of ZNF185 decreased significantly in human glioma tissues compared to that of tumor adjacent tissues(P<0.01). The over expression of ZNF185 in SF767 resulted in the increased proportion of cell cycle G0-G1phase, but decreased proportion of S phase(P<0.05). Furthermore, the cell proliferation was significantly inhibited in the ZNF185 over-expressed SF767 cells compared with that of blank vector transfected cells(P<0.05). Con?clusion ZNF185 plays an inhibitory role in cell proliferation of human brain glioma cells.

ZFP580, a novel transcription factor, is involved in cardioprotection of hypoxic preconditioning against hypoxia-reoxygenation injury in myocar-dial cells / 中国病理生理杂志

AIM:To elucidate whether ZFP580 is involved in the cardioprotective effects of hypoxic precondi-tioning (HPC) against hypoxia-reoxygenation (H/R) injury in H9c2 myocardial cells.METHODS: Rat heart-derived H9c2 cells were cultured in DMEM .H/R was induced by incubation under ischemic hypoxia for 3 h and reoxygenation for 2 h.HPC was induced by exposing the H 9c2 cells to 10 min of hypoxia and 20 min of reoxygenation for 3 cycles before H/R treatment.MTT staining and LDH leakage detection were used to evaluate the effects of HPC .Western blotting was used to detect the protein levels of ZFP580, phosphorylated ERK1/2 and cleaved caspased-3.The effects of ZFP580 overexpre-ssion or knockdown on H/R induced apoptosis were determined .RESULTS:The results of MTT staining and LDH leakage detection showed evidence of HPC cytoprotection against H /R-induced cell death in H9c2 cells.ZFP580 protein level and ERK1/2 phosphorylation were significantly increased in the HPC group compared with control group and H /R group. PD98059, an inhibitor of ERK1/2 phosphorylation , significantly suppressed the HPC-induced up-regulation of ZFP580 pro-tein expression.ZFP580 overexpression significantly inhibited apoptosis and caspase-3 activation in H9c2 cells.CON-CLUSION:HPC exhibits cytoprotection against H/R and leads to high level of ZFP 580 protein in H9c2 cells.ZFP580 is regulated by ERK1/2 activation and mediates the anti-apoptotic effect of the ERK1/2 signaling pathway in HPC cytoprotec-tion.

ZHX2 and cancer / 国际肿瘤学杂志

Transcription repressor ZHX2 is one of the members in ZHX protein family,which exists widely in human tissue and participates in the occurrence and development of various diseases.Researches show that ZHX2 is closely related to the occurrence and development of cancers,such as liver cancer,multiple myeloma,gastric cancer and colorectal cancer,which has the potential value of tumor treatment.

Role of Zinc in an Organism and Its Influence on Processes Leading to Apoptosis.

This review brings together and analyzes the problem of zinc effects on the body through apoptosis, also affecting the latest data in the study of process itself apoptosis. Also, the possibility of using zinc and its derivatives and its complexes in cancer treatment are discussed. The review also focuses on the biochemical problems that lead to various diseases occurring in conditions of excess or deficiency of intracellular zinc. Review includes more than 300 references and contains research over the past ~ 15 years, focusing on the latest data.

Experimental study of zinc finger protein A20 inhibiting oxidized low density lipoprotein induced migration in smooth muscle cell / 中国医师杂志

Objective To investigate the possible mechanisms of ox-LDL on vascular smooth muscle cells (VSMC) with and without exogenous zinc finger protein A20 gene. Methods VSMC were trans-fected with plamid containing A20 gene and incubated with ox-LDL. TLR4 and LOX-1 mRNA expression were measured by RT-PCR. Results After VSMC incubated with ox-LDL, the expression of LOX-1 and TLR-4 mRNA reached a higher level. However, when VSMC were transfected with plasmid containing A20 gene, the NF-kB nuclear translocation and the ability of migration reduced to normal level. Conclusions ox-LDL can significantly activate NF-kB signaling system and enhance migration in VSMC. The activation may induce the inflammatory response in arterial wall, the migration of VSMC to the intima, and triggering the process of atherosclerosis. Transfecting plasmid containing A20 gene significantly inhibited the activation of NF-kB and the ability of migration of VSMC. A20 effects might be through inhibiting NF-kB signaling. Meanwhile, A20 blocked the development of atherosclerosis.

PIAS1 interacts with the KRAB zinc finger protein, ZNF133, via zinc finger motifs and regulates its transcriptional activity

Zinc finger protein 133 (ZNF133) is composed of a Kruppel-associated box (KRAB) domain and 14 contiguous zinc finger motifs. ZNF133 is regarded as a transcriptional repressor because the KRAB domain has potent repressor activity and the zinc finger motifs usually act in binding to DNA. However, we found that the zinc finger motifs of ZNF133 also possessed transcriptional repressor activity. By two-hybrid screening assay, we found that the zinc finger motifs of ZNF133 interacted with protein inhibitor of activated STAT1 (PIAS1). PIAS1 enhanced the transcriptional repression activity of ZNF133 through the zinc finger motifs. This effect of PIAS1 was relieved by an inhibitor of the histone deacetylases (HDACs). These results demonstrate that the transcriptional repressor activity of ZNF133 is regulated by both the KRAB domain and the zinc finger motifs, and that the repressive effect by zinc finger motifs is mediated by PIAS1.