CHA2DS2-VASc-HSF Score as a Predictor of Severity of Coronary Artery Disease in Patients Undergoing Coronary Angiography

Background: Cardiovascular atherosclerosis, particularly coronary artery disease (CAD), represents the main reason for death prematurely over the world. Risk stratification and prevention by risk factor modification are crucial aspects of CAD therapy. The CHADS2 and CHA2DS2-VASc scores are effective in determining the risk of thrombosis in non-valvular atrial fibrillation (AF). The current research aimed to determine the CHA2 DS2-VASc-HSF score as a predictor for CAD severity in CAD patients after coronary angiography. Methods: This cross-sectional study was assessed on 100 patients who attended the coronary care unit and underwent coronary angiography. They were categorised into three groups: Group I: Low syntax scores (2-13), Group II: Intermediate syntax score (14-20), and Group III: High syntax score (21-40). Results: Our study showed that the SYNTAX score revealed a statistically significant relation with patient's age, gender, and presentation. Regarding the medical history of the studied participant in relation to SYNTAX score, most patients reported a history of HTN, DM, Dyslipidemia, CHF, and previous history of vascular disease showed intermediate and high SYNTAX score in comparison to those with normal blood pressure, glucose level, lipid profile, no CHF history and those no previous history. SYNTAX score showed significant relation with ejection fraction and CHA2 DS2-VASc-HSF score of the patient. Significant low ejection fraction in high SYNTAX score patients compared to low SYNTAX score patients. Significant high average of CHA2 DS2-VASc-HSF score among those with high and intermediate SYNTAX score compared to those with low SYNTAX score. Conclusions: CHA2DS2-VASc-HSF should be constituted as the ideal scoring scheme for predicting the severity of CAD. Risk scoring systems may be effective as predictors due to their simplicity and easy employment by physicians in ordinary practice without incurring additional costs

Identification of heat stress transcription factors gene family in Setcreasea purpurea and analysis of its expression pattern under Cu2+ stress / 生物工程学报

Heat stress transcription factors (Hsf) family is one of the most important transcription factor families in plants, and plays an important role in the growth and development of plants when encountering abiotic stresses such as heat, drought, and heavy metals. In this study, 20 SpbHsf genes were identified from the full-length transcriptome database of Setcreasea purpurea, and the structure and function of the Hsf gene family were analyzed using bioinformatics tools and qRT-PCR. The results showed that all SpbHsf proteins were hydrophilic. There were 12 SpbHsf proteins located in the nucleus, and the content of α-helix and random coil in the secondary structure of all SpbHsf proteins was high. The SpbHsf genes are divided into three subfamilies, each of which contains unique conserved motifs. All SpbHsf proteins contain DBD and HR-A/B domains. Phylogenetic analysis showed that OsHsf in Oryza sativa protein had the highest homology with SpbHsf protein. All the 20 SpbHsf genes were expressed in the root tissues of S. purpurea. Among them, 8 were significantly up-regulated while 8 were significantly down-regulated under Cu2+ stress. This study may help better understand the function and expression pattern of the S. purpurea Hsf gene family.

Effects of FBXW7α on Expression and Localization of Heat Shock Transcription Factor 1 in Colorectal Cancer Cells / 肿瘤防治研究

Objective To investigate the effect of FBXW7 on the expression and localization of HSF1 in colorectal cancer cells. Methods The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 deletion (KO) and wild-type (WT) FBXW7-expressing counterpart colorectal cancer cells were detected by Western blot. The nucleoprotein expression and localization of pHSF1Ser326 in heat-shocked or recovery stage cells were observed by Western blot and immunofluorescence method. Results The HSF1 expression level in DLD1 cells transfected with FBXW7α was decreased significantly (P < 0.01). The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 KO cells were higher than those in WT cells (all P < 0.05). HSF1 and pHSF1Ser326 in FBXW7 KO cells were mainly expressed in nucleus and weakly expressed in cytoplasm. After warm stimulation, the expression of HSF1 and pHSF1Ser326 in WT cells recovered to the unstimulated level, while the expression of HSF1 and pHSF1Ser326 in FBXW7 KO cells were higher in the nucleus (all P < 0.01). Conclusion Loss of FBXW7 could affect the nuclear HSF1 recovery after warm stimulation. It may be associated with FBXW7 deletion inhibiting the degradation of nuclear HSF1.

Screening of pathogenic mutation in a Chinese family with congenital pulverulent cataract / 中华实验眼科杂志

Objective@#To analysis the pathogenic mutation and the clinical characteristics of a three generation family with congenital pulverulent cataract.@*Methods@#A congenital cataract family was chosen from the First Affiliated Hospital of AnHui Medical University, 5 ml peripheral blood was obtained from each family member to extract genomic DNA.Next generation sequencing was used to detect the mutation in proband (Ⅱ5), Ⅱ6 and Ⅲ8, and Sanger sequencing was applied to verify pathogenic mutation in the whole family members.The mutation site was compared with the gene sequence of 10 000 normal Chinese.PolyPhen-2 and SIFT were applied to analysis the alteration on the protein structure and function and its possible pathogenesis.This study followed the Declaration of Helsinki and was approved by the Ethics Committee of AnHui Medical University (NO.PJ2017-5-17). All patients signed informed consent.@*Results@#The pedigree consisted of 19 members of three generations, including 10 patients and 9 normal family members.Heterozygous mutation of GJA3 gene c. 427G>A (p.G143R) was detected in all patients of the pedigree, but was not found in normal members of the pedigree and 10 000 normal Chinese.The score calculated from SIFT and PolyPhen-2 indicated that the mutation probably had malignant effect on normal protein structure, Swiss-model website analysis showed that the mutation likely altered the secondary structure of the protein CX 46 by reducing an α-helix between 107-115 amino acids.Meanwhile, c.1325-1G>T mutation of HSF4 gene were detected in Ⅱ5 and Ⅲ8, which was not found in other family members and 10 000 normal Chinese.HSF and MaxEntScan results showed that the mutation probably had serious effect on the splicing of mRNA.The cataract development rates of Ⅱ5 and Ⅲ8 were faster than that of the same age in the same generation of the pedigree, and the morphology of lens opacity was changed.@*Conclusions@#The heterozygous c. 427G>A mutation in GJA3 gene is responsible for pulverulent cataract in this family, meanwhile the c. 1325-1G>T mutation in HSF4 gene may change the type of phacoscotasmus and accelerate the progress of disease.

Screening of pathogenic mutation in a Chinese family with congenital pulverulent cataract / 中华实验眼科杂志

Objective To analysis the pathogenic mutation and the clinical characteristics of a three generation family with congenital pulverulent cataract. Methods A congenital cataract family was chosen from the First Affiliated Hospital of AnHui Medical University,5 ml peripheral blood was obtained from each family member to extract genomic DNA. Next generation sequencing was used to detect the mutation in proband (Ⅱ5),Ⅱ6 and Ⅲ8, and Sanger sequencing was applied to verify pathogenic mutation in the whole family members. The mutation site was compared with the gene sequence of 10000 normal Chinese. PolyPhen-2 and SIFT were applied to analysis the alteration on the protein structure and function and its possible pathogenesis. This study followed the Declaration of Helsinki and was approved by the Ethics Committee of AnHui Medical University ( NO. PJ2017-5-17 ) . All patients signed informed consent. Results The pedigree consisted of 19 members of three generations,including 10 patients and 9 normal family members. Heterozygous mutation of GJA3 gene c. 427G>A ( p. G143R) was detected in all patients of the pedigree,but was not found in normal members of the pedigree and 10000 normal Chinese. The score calculated from SIFT and PolyPhen-2 indicated that the mutation probably had malignant effect on normal protein structure,Swiss-model website analysis showed that the mutation likely altered the secondary structure of the protein CX 46 by reducing anα-helix between 107-115 amino acids. Meanwhile,c. 1325-1G>T mutation of HSF4 gene were detected in Ⅱ5 and Ⅲ8, which was not found in other family members and 10000 normal Chinese. HSF and MaxEntScan results showed that the mutation probably had serious effect on the splicing of mRNA. The cataract development rates of Ⅱ5 andⅢ8 were faster than that of the same age in the same generation of the pedigree,and the morphology of lens opacity was changed. Conclusions The heterozygous c. 427G>A mutation in GJA3 gene is responsible for pulverulent cataract in this family,meanwhile the c. 1325-1G>T mutation in HSF4 gene may change the type of phacoscotasmus and accelerate the progress of disease.

Heat Shock Factor 1 Predicts Poor Prognosis of Gastric Cancer

PURPOSE: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer. MATERIALS AND METHODS: The expression levels of HSF1 in normal and gastric cancer tissues were compared using cDNA microarray data from the NCBI Gene Expression Omnibus (GEO) dataset. The proliferation of gastric cancer cells was analyzed using the WST assay. Transwell migration and invasion assays were used to evaluate the migration and invasion abilities of gastric cancer cells. Protein levels of HSF1 were analyzed using immunohistochemical staining of tissue microarrays from patients with gastric cancer. RESULTS: HSF1 expression was significantly higher in gastric cancer tissue than in normal tissue. Knockdown of HSF1 reduced the proliferation, migration, and invasion of gastric cancer cells, while HSF1 overexpression promoted proliferation, migration, and invasion of gastric cancer cells. Furthermore, HSF1 promoted the proliferation of gastric cancer cells in vivo. In Kaplan-Meier analysis, high levels of HSF1 were associated with poor prognosis for patients with gastric cancer (p=0.028). CONCLUSION: HSF1 may be closely associated with the proliferation and motility of gastric cancer cells and poor prognosis of patients with gastric cancer. Accordingly, HSF1 could serve as a prognostic marker for gastric cancer.

The impact of HSF on endometrium

Summary Objective: We conducted the research in order to explore the impact of hydrosalpinx fluid (HSF) on endometrium. Method: HSF group: 261 patients with HSF scheduled to undergo laparoscopic surgery 3 to 7 days after menstruation in our center. Hysteroscopy would also be performed in order to observe the endometrial morphology during the surgery. Sixty (60) patients would be randomly selected for endometrial biopsy in order to detect the inflammatory cytokines TNF-a and IL-2 mRNA. Non-HSF group: 210 patients with no evidence of HSF due to chronic salpingitis or pelvic adhesion. IVF-ET treatment was performed after eliminating the factor of male infertility and hysteroscopy was conducted before the treatment. Fifty (50) patients underwent endometrial biopsy in order to detect TNF-a and IL-2 mRNA. Results: Hysteroscopy was performed in 261 patients with HSF and 210 patients without HSF. The incidence rate of endometritis manifestation among these two groups of patients was 37.2% (97/261) and 20.5% (43/210), respectively. The incidence rate of endometritis in the patients with HSF is significantly higher than in the patients without HSF (p<0.05). Sixty (60) patients from the HSF group and 50 patients from the non-HSF group were regrouped according to inflammatory and normal manifestation after the endometrial biopsy. There were 49 patients in the inflammatory manifestation group and 61 patients in the normal manifestation group. RT-PCR technology was adopted to detect the expression of inflammatory cytokines TNF-a and IL-2 mRNA in endometrial tissue. The level of TNF-a mRNA expression in endometrial tissues with inflammatory manifestation was higher than in normal endometrium (76.75±11.95 vs. 23.45±9.75, p<0.01). There are significant differences between them. The level of IL-2 mRNA expression in endometrial tissues with inflammatory manifestation was higher than that found in normal endometrium (80.56±13.35 vs. 35.12±8.35, p<0.01). There are significant differences between them. Conclusion: Chronic endometritis is related to HSF and may therefore affect endometrial receptivity.

The expressions of HSFl and XAF1 in endometrial carcinoma and their correlation analysis / 西安交通大学学报(医学版)

ABSTRACT:Objective To test the expressions of heat shock transcription factor 1 (HSF1 )and XIAP-associated factor 1 (XAF1 )in different endometrial tissues,and analyze the association between their expressions and the clinicopathological features of this malignancy.Methods The expressions of HSF1 and XAF1 in 64 cases of endometria1 carcinoma (EC group)and 33 cases of normal endometrial tissues (NE group)were detected with immunohistochemistry S-P method.The correlation was observed.Results The positive expression rate of HSF1 was much higher in EC group than in NE group (76.6% vs .36.4%,P <0.05).The positive rate of XAF1 was 31.2% in EC group and 72.7% in NE group (P <0.05).The positive expressions of HSF1 and different subgroups of histological grade,myometrial invasion and lymph node metastasis were significantly different (P <0.05)in EC group.The positive expressions of XAF1 and different subgroups of histological grade,myometrial invasion,clinical stage and lymph node metastasis were significantly different (P < 0.05 )in EC group.There was a negative correlation between HSF1 and XAF1 in EC group (P <0.05).Conclusion In EC group,the high expression of HSF1 may inhibit the growth of XAF1 expression,cause excessive growth of cancer cells,reduce the apoptosis of cancer cells,and finally lead to the further development of tumors.

Regulatory fe fect of Hsf1 on PLC/PRF5 hepa toma cells proliferation / 中国免疫学杂志

Objective:To explore the regulatory effect of Hsf 1 on PLC/PRF5 hepatoma cells proliferation.Methods: By shRNA gene silencing technology ,constructed PLC/PRF5 hepatoma cell line of Hsf 1 gene silencing.To detect the expression of Hsf 1, p53 and Rb proteins in PLC/PRF5 hepatoma cells by Western blot.The proliferation of PLC/PRF5 cell line was observed by methylthiazolyl tetrazolium assay ( MTT ) , plate clone formation assay ( PCFA ) and cell cycle assay.Results: shRNA-Hsf1 could significantly inhibit the expression of Hsf 1 in PLC/PRF5 cells.It could induce PLC/PRF5 cells stopping at G1 phase of cell cycle , inhibit cell proliferation and colonal formation;silencing Hsf1 caused up-regulation of p53 and Rb proteins expression in PLC/PRF5 cells.Conclusion: Silencing Hsf1 is involved in up-regulation of p53 and Rb proteins expression , which results in inhibiting proliferation of PLC/PRF5 hepatoma cells.

Bis is Induced by Oxidative Stress via Activation of HSF1

The Bis protein is known to be involved in a variety of cellular processes including apoptosis, migration, autophagy as well as protein quality control. Bis expression is induced in response to a number of types of stress, such as heat shock or a proteasome inhibitor via the activation of heat shock factor (HSF)1. We report herein that Bis expression is increased at the transcriptional level in HK-2 kidney tubular cells and A172 glioma cells by exposure to oxidative stress such as H2O2 treatment and oxygen-glucose deprivation, respectively. The pretreatment of HK-2 cells with N-acetyl cysteine, suppressed Bis induction. Furthermore, HSF1 silencing attenuated Bis expression that was induced by H2O2, accompaniedby increase in reactive oxygen species (ROS) accumulation. Using a series of deletion constructs of the bis gene promoter, two putative heat shock elements located in the proximal region of the bis gene promoter were found to be essential for the constitutive expression is as well as the inducible expression of Bis. Taken together, our results indicate that oxidative stress induces Bis expression at the transcriptional levels via activation of HSF1, which might confer an expansion of antioxidant capacity against pro-oxidant milieu. However, the possible role of the other cis-element in the induction of Bis remains to be determined.

Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in MDR cells

MDR1 promoter has been shown to contain heat shock elements (HSE), and it has been reported that FM3A/M and P388/M MDR cells show a constitutively activated heat shock factor (HSF), suggesting that HSF might be an important target for reversing the multidrug resistance. Therefore, it was examined whether quercetin, which has been shown to interfere with the formation of the complex between HSE and HSF, and to downregulate the level of HSF1, can sensitize MDR cells against anticancer drugs by inhibition of HSF DNA-binding activity. In this study, quercetin appeared to inhibit the constitutive HSF DNA-binding activity and the sodium arsenite-induced HSF DNA-binding activity in the MDR cells. The basal and sodium arsenite-induced MDRCAT activities were remarkably suppressed by the treatment of quercetin. These results were well consistent with the finding that the treatment of quercetin decreased the expression level of P-gp, MDR1 gene product, in dose-dependent manner, and markedly increased the sensitivity of MDR cells to vincristine or vinblastine. These results suggest that quercetin can decrease the expression of P-gp via inhibition of HSF DNA-binding activity, and might be useful as a chemosensitizer in MDR cells.

Role of heat shock transcription factors in stress response and during development.

A variety of physical and chemical stimuli were known to cause specific stress response in all organisms. Research done over the past 25 years has shown that there is a striking uniformity in the manner in which organisms respond to different forms of stress. Expression of stress responsive genes was shown to be regulated by two or more specific transcription factors present in the cell prior to stress. These specific genes were also activated during development. In this review, the role of heat shock transcription factors in stress response, during development and during cell cycle is described.

Effect of the polymerization of HSF1 on the febrile response and the content of vasopressin arginine in brain in LPS-induced fever rabbits / 中国药理学通报

Aim To observe the effect of the polymerization of HSF1 on the febrile response in fever rabbits,and further to investigate HSF1 action in thermoregulation and the possible central mechanism.Methods 70 rabbits were divided randomly into 4 groups:the control group(N),the quercetin group(Q),the LPS-feverish group(L),the quercetin+LPS-feverish group(Q+L).Changes in body temperature were continually observed;the expression of HSF1 and HSP70 in hypothalamus was detected by Western blot;the content of AVP in hypothalamus and VSA was measured by radioimmunoassay.Results ① The sequence of the maximum change of temperature(△Tmax)from low to high:group Q